Ultraflex stent--benefits and risks in ultimate palliation of advanced, malignant stenosis in the esophagus.

BACKGROUND/AIMS: Sophisticated endoscopical palliation in end-stage malignant stenosis of the esophagus and gastroesophageal-junction must be weighed against associated morbidity and mortality. In a prospective study we investigated benefits and risks of one type of coated, self-expandable stent in ultimate palliation of esophageal neoplasms focusing on factors that might predispose patients to develop complications. METHODOLOGY: 33 men (70.2%) and 14 women (29.8%), (mean age 68.3 years, range from 38 to 90 years), suffering from nonresectable malignant stenosis of the esophagus due to advanced tumor stage and/or functional inoperability were treated by using a covered, self-expandable stent (covered ULTRAFLEX esophageal stent system, Microinvasive, Boston Scientific Corporation, Boston, MA). Stenting was indicated because of severe dysphagia for liquids and saliva in 41 (87.2%) patients, tracheoesophageal fistula in 5 (10.6%) patients and in one case of tumor bleeding (2.1%). 32 out of 47 patients had had one or other multiple treatment modalities before stenting. In 15 patients stenting was the first and only therapeutic option. RESULTS: All patients experienced an improvement of dysphagia immediately after stenting. Eight out of 47 patients (17.1%) developed major stent-associated complications: Early complications within 4 days after implantation evolved in two cases, with one patient dying from stent-induced perforation with consecutive mediastinitis and multi-organ failure. Late complications (20 to 180 days after stent implantation) occurred in 6 cases: Three esophagotracheal fistulae (two with tracheal compression) induced by stent expansion, one stent-induced bleeding and two stent dislocations. After appropriate complication management all but two patients were able to be discharged after a mean of 2.6 days. Multivariate analysis did not show any factors that might have predicted the development of major stent-associated complications. CONCLUSIONS: Implantation of the self-expandable Ultraflex-stent will efficiently palliate dysphagia, bleeding and fistulae. The 17% risk of major complications seems acceptable regarding the inherent problems of alternative treatment options, like gastrostomy, PEG, nasogastric tube or long-term parenteral feeding.

Penetration of piperacillin and tazobactam into pneumonic human lung tissue measured by in vivo microdialysis.

OBJECTIVES: The pharmacokinetic profile of antibiotics at the site of anti-infective action is one of the most important determinants of drug response, since it correlates with antimicrobial effect. Up to now, only limited information on the lung tissue pharmacokinetics of antibiotic agents has been available. The aim of this study was to measure, using a new microdialysis-based approach, antibiotic penetration into the extracellular space fluid of pneumonic human lung parenchyma. PATIENTS AND METHODS: The lung penetration of a combination of piperacillin and tazobactam, substances with low protein binding, was determined in five patients suffering from pneumonia and metapneumonic pleural empyema. The condition was treated by decortication after lateral thoracotomy. Intra-, or post-operatively, respectively, two microdialysis probes were inserted into pneumonic lung tissue, and into healthy skeletal muscle to obtain reference values. Serum and microdialysis samples were collected at 20-min intervals for at last 8 h following i.v. administration of a single dose of 4 g piperacillin and 500 mg tazobactam. RESULTS: The mean free interstitial concentration profiles of piperacillin in infected lung tissue and serum showed a maximal tissue concentration (Cmax) of 176.0 +/- 105.0 mg l-1 and 326.0 +/- 60.6 mg l-1, respectively. The mean AUC (area under the curve) for infected lung tissue was 288.0 +/- 167.0 mg.h l-1 and for serum 470.0 +/- 142.0 mg.h l-1. There was a statistically significant difference between AUC (lung) and AUC (serum) (P = 0.018) as well as between AUC (lung) and AUC (muscle) (P = 0.043). The intrapulmonary concentrations of piperacillin and tazobactam exceeded the minimum inhibitory concentrations (MIC) for most relevant bacteria for 4-6 h. The procedure was well tolerated by all patients and no adverse events or microdialysis-associated side-effects were observed. CONCLUSION: This microdialysis technique enabled continuous tissue pharmacokinetic measurement of free, unbound anti-infective agents in the lung tissue of patients with pneumonia. The present data corroborate the use of piperacillin and tazobactam in the treatment of lung infections caused by extracellular bacteria and demonstrate the distribution of piperacillin and tazobactam in the interstitial space of pneumonic lung tissue.