Lymphatic metastasis contributes to mortality from solid tumors. Whether metastasizing cancer cells reach lymph nodes via intratumor lymphatic vessels is unknown. Here, we examine functional lymphatics associated with mouse tumors expressing normal or elevated levels of vascular endothelial growth factor-C (VEGF-C), a molecule that stimulates lymphangiogenesis. Although VEGF-C overexpression increased lymphatic surface area in the tumor margin and lymphatic metastasis, these tumors contained no functional lymphatics, as assessed by four independent functional assays and immunohistochemical staining. These findings suggest that the functional lymphatics in the tumor margin alone are sufficient for lymphatic metastasis and should be targeted therapeutically.
A total of 503 patients underwent 521 tracheal resections and reconstructions for postintubation stenosis from 1965 through 1992. Fifty-three had had prior attempts at surgical resection, 51 others had undergone various forms of tracheal or laryngeal repair, and 45 had had laser treatment. There were 251 cuff lesions, 178 stomal lesions, 38 at both levels, and 36 of indeterminate origin. Sixty-two patients with major laryngeal injuries required complete resection of anterior cricoid cartilage and anastomosis of trachea to thyroid cartilage, and 117 had tracheal anastomosis to the cricoid. A cervical approach was used in 350, cervicomediastinal in 145, and transthoracic in 8. Length of resection was 1.0 to 7.5 cm. Forty-nine had laryngeal release to reduce anastomotic tension. A total of 471 patients (93.7%) had good (87.5%) or satisfactory (6.2%) results. Eighteen of 37 whose operation failed underwent a second reconstruction. Eighteen required postoperative tracheostomy or T-tube insertion for extensive or multilevel disease. Twelve died (2.4%). The most common complication, suture line granulations (9.7%), has almost vanished with the use of absorbable sutures. Wound infection occurred in 15 (3%) and glottic dysfunction in 11 (2.2%). Five had postoperative innominate artery hemorrhage. Resection and reconstruction offer optimal treatment for postintubation tracheal stenosis.
Acquired TEF is a rare complication that can occur from a variety of causes. The most common etiology of nonmalignant TEF is as a complication of intubation with cuff-related tracheal injury. Most patients present with increased secretions, pneumonia, and evidence of aspiration of gastric contents while the patient is on mechanical ventilation. When diagnosed after extubation, the most frequent sign of TEF is coughing after swallowing. A high index of suspicion is required in patients at risk for developing a TEF. The diagnostic evaluation is by bronchoscopy and esophagoscopy. When the diagnosis has been made, the immediate goal should be to minimize tracheobronchial soilage by placing the cuff of a tracheostomy tube distal to the fistula. Reflux of gastric contents is diminished by placement of a gastrostomy tube, and adequate nutrition is facilitated by inserting a jejunostomy tube. Surgical correction is required because spontaneous closure is rare, but surgery should be postponed until the patient is weaned from mechanical ventilation because positive pressure ventilation after tracheal repair carries an increased risk of anastomotic dehiscence and restenosis. An anterior cervical collar incision can be used for most cases of post-intubation TEFs. The esophagus should be closed in two layers over a nasogastric tube and buttressed with a pedicled strap muscle flap. If the tracheal defect is small, primary repair can be employed. In most cases, however, the best results can be achieved with tracheal resection and reconstruction. The patient should be extubated at the completion of the case, if possible. With this strategy, as first described by Grillo and colleagues [27], single-stage repair can be performed safely and with a high success rate. Malignant TEFs cannot be cured because of the underlying incurable disease process. As with nonmalignant TEFs, the principal complications are tracheo-bronchial contamination and poor nutrition. Without prompt palliation, death occurs rapidly, with a mean survival time of between 1 and 6 weeks in patients who are treated with supportive care alone. The most common primary tumor causing malignant TEF is esophageal carcinoma. The other frequent cause is lung cancer. Patients present with signs and symptoms typical of TEF, including coughing after swallowing. Diagnosis is made by barium esophagography, and the location and size of the fistula is determined by bronchoscopy and esophagoscopy. Treatment must correct the two problems of airway contamination and poor nutrition. The most effective treatments are esophageal bypass and esophageal stenting. Bypass is demonstrated to resolve respiratory soilage and allow fairly normal swallowing, but it should be reserved for patients who can tolerate a major operation. Stenting can be offered to nearly all patients regardless of their physiologic condition. Stenting also limits aspiration and allows swallowing. Esophageal exclusion is rarely indicated in the current era of familiarity with stenting techniques. Direct fistula closure...
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