ABSTRACT
BACKGROUND: Metallic stents for malignant biliary obstruction are susceptible to occlusion by tumor ingrowth or overgrowth. Paclitaxel-eluting metallic stents (PEMSs), however, may prevent occlusion from tumor ingrowth. OBJECTIVE: We evaluated the safety of PEMSs in a canine biliary model by analyzing tissue reactions by histologic examination. DESIGN: Animal study. SETTING AND INTERVENTIONS: Six PEMSs and 5 control stents (CSs) were endoscopically placed in the bile ducts of 11 mongrel dogs and followed up for 6 weeks. MAIN OUTCOME MEASUREMENTS: The animals were euthanized at 6 weeks, and gross and microhistologic examinations were done. A comparison was made between dogs with PEMSs and dogs with CSs. RESULTS: All 11 stents were successfully placed in the bile ducts, although the distal ends of 2 PEMSs were partially exposed to the duodenal lumen. All 11 dogs survived until death without evidence of jaundice. Gross histologic examination showed mucosal hyperplasia in 3 of 6 dogs in the PEMS group, but there was no evidence of mucosal hyperplasia in the CS group. Microscopically, the epithelial layers at the middle and distal ends of the stented segments were significantly thicker in the PEMS dogs than in the CS group. CONCLUSIONS: Placement of PEMSs in normal canine bile ducts was without significant technical complications; however, local drug delivery from the PEMS resulted in significant histologic changes. Therefore, it is important to choose a drug in adequate concentrations to exert an antitumor effect without damaging the adjacent normal bilary mucosa.
Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Coated Materials, Biocompatible , Common Bile Duct/drug effects , Common Bile Duct/pathology , Disease Models, Animal , Drug-Eluting Stents , Paclitaxel/administration & dosage , Polyurethanes , Animals , Dogs , Epithelium/drug effects , Epithelium/pathology , Equipment Safety , Hyperplasia/chemically induced , Hyperplasia/pathology , Male , Mucous Membrane/drug effects , Mucous Membrane/pathologyABSTRACT
BACKGROUND: Paclitaxel, with its antitumor effect, may improve the function of metallic stents used for biliary drainage. However, clinical studies that use metallic stents covered with a paclitaxel-incorporated membrane (MSCPM) in the biliary tract of human beings have not been previously carried out. OBJECTIVE: To evaluate the safety and efficacy of an MSCPM for patients with malignant biliary obstruction. DESIGN AND SETTING: A case series that includes 4 endoscopy centers. PATIENTS: From July 2003 to August 2006, a total of 21 patients diagnosed with unresectable malignant biliary obstruction. INTERVENTION: Endoscopic placement of an MSCPM. MAIN OUTCOME MEASUREMENTS: Stent occlusion, complications, stent patency, patient survival, and the periodic mean concentration of paclitaxel in the blood. RESULTS: Occlusion of the MSCPM was observed in 9 patients and was caused by bile sludge or clog in 4, tumor overgrowth in 3, and tumor ingrowth in 2. Complications included obstructive jaundice in 6, cholangitis in 3, and 1 patient showed stent migration with cholecystitis. The mean patency of a MSCPM was 429 days (median 270 days, range 68-810 days) and cumulative patency rates at 3, 6, and 12 months were 100%, 71%, and 36%, respectively. The mean survival of patients was 350 days (median 281 days, range 68-811 days). The highest concentration of paclitaxel in the blood was found between 1 and 10 days after insertion. LIMITATIONS: Small number of patients and low rate of pathologic diagnosis. CONCLUSIONS: The endoscopic insertion of MSCPM is technically feasible, safe, and effective in patients with malignant biliary obstruction. In addition, MSCPM may exert local antitumor activity because of the steady release of paclitaxel.
