The effect of paclitaxel-eluting covered metal stents versus covered metal stents in a rabbit esophageal squamous carcinoma model

Abstract

BackgroundThe use of self-expanding metallic stents (SEMSs) is the current treatment of choice for malignant gastrointestinal obstructions. However, these stents can promote only drainage and have no antitumor effect. Some studies have reported that drug-eluting SEMSs may have tumor inhibition potential. The aim of this study was to evaluate the efficiency and safety of paclitaxel-eluting SEMSs (PEMSs) in rabbit esophageal cancer models.Materials and methodsA PEMS was covered with a paclitaxel-incorporated membrane, in which the concentration of paclitaxel was 10% (wt/vol). The rabbit models were created endoscopically. Then, a PEMS or SEMS was endoscopically inserted into the rabbit esophagus. Two weeks after stent placement, the rabbits were sacrificed, and we evaluated the tumor volume, area of the wall defect, area of the tumor under endoscopic ultrasound (EUS) before and after stent placement, status of the proximal esophageal obstruction, tumor metastasis food-intake and weight loss.ResultsA total of 26 rabbits received stent insertion and survived until sacrifice, and migration occurred in 4 cases, 3 in SEMS group and 1 in PEMS group. For the remaining 22 rabbits, at the sacrificed time, the average tumor volume was 7.00±4.30 cm3 in the SEMS group and 0.94±1.51 cm3 in the PEMS group (P<0.05). The area of the esophageal wall defect was 0.70±0.63 cm2 in the SEMS group and 0.17±0.16 cm2 in the PEMS group (P<0.05). The tumor area under EUS was 4.40±1.47 cm2 in the SEMS group and 1.30±1.06 cm2 in the PEMS group (P<0.05). At the time of stent placement, tumor area under EUS was comparable in the two groups. Other indices did not significantly differ between the two groups.ConclusionsSEMS and PEMS are both safe and effective to relieve dysphagia in rabbit esophageal cancer models. A PEMS can serve as an alternative tool for advanced esophageal cancer that may inhibit tumor growth by serving as a drug sustained-release platform. Clinical trials of the stent are warranted in the future.

A Review of Self-Expanding Esophageal Stents for the Palliation Therapy of Inoperable Esophageal Malignancies

“…For those patients with inoperable esophageal malignancies, using a SEMS to mechanically open the blocked esophagus for drinking and feeding has become the primary palliative therapy of dysphagia [6]. Recently, drug-eluting self-expanding metallic stents (DE-SEMS) have been attempted with some efficacy for the management of occlusion of the esophagus beyond just palliative procedure [7, 8]. DE-SEMS, a drug-loaded polymer membrane coated SEMS, provides both the mechanical support to expand the blocked esophagus, and the released anticancer drug to inhibit tumor growth, which has been proven to prolong patient life-span[11].…”

“…A local, more targeted release of an anticancer drug from a bilayered or multilayered drug-releasing films demonstrated enhanced efficacy of anticancer drugs, prevented or reduced the side effects associated with systemic administration of an anticancer drug, such as paclitaxel, 5-fluorouracil, and gemcitabine [7, 11, 60–62]. Therefore, this type of drug-eluting stent has potential for improving inhibition of esophageal tumor growth.…”

“…To open the occluded esophagus, a self-expanding esophageal stent is often used for drinking and feeding, which has become the primary palliative therapy of dysphagia [6]. Beyond just palliative therapy, researchers are exploring new therapeutic applications for an esophageal stent by wrapping a drug-eluting polymer film on the device [7, 8]. This wrapping polymer film provides the release of an anticancer drug to inhibit tumor growth.…”

Stenting for Advanced Esophageal Carcinoma

“…54 Zhang et al reported the effects of paclitaxel-eluting metallic stent (PEMS) in normal esophagus and in a rabbit esophageal squamous carcinoma model in their serial studies. 55,56 Their results showed that PEMS slowed tumor growth and thereby can serve as an alternative tool for esophageal cancer. However, the molecular mechanism of the antitumor effect was not clear in their study.…”

Esophageal stenting for unresectable cancer (review of literature)

“…Разработана двуслойная полимерная пленка из биосовместимого полиуретана с включением доцетаксела, которая может стать покрытием для СМС [46]. Исследования стентов с полимерным покрытием, содержащим паклитаксел, на кроликах продемонстрировали впечатляющее уменьшение размеров и объема опухоли [47,48]. В другом исследовании на свиной модели были протестированы стенты с покрытием, содержащим 5-фторурацил или паклитаксел, причем удалось достичь высокой концентрации действующего вещества в опухоли без повреждения слизистой пищевода [49].…”