The Efficacy Of Tracheal MMC Eluting Stent In Decreasing The Granulation Tissue Hyperplasia Secondary To Stent Placement

The management of tracheal stenosis (TS) is difficult. Localized TS can betreated by surgical treatment. However, surgical treatment is not effective forsome kinds of TS, including TS caused by tumor, TS involved with differentlocations, long segmental TS, recurrent TS and TS in poor risk patients. Inrecently, a great progress has been made by the use of airway stent, especiallymetallic airway stent, in the management of TS. But there have been manyreports about stent-related complications since the use of stent has beenintroduced, such as granulation tissue hyperplasia, stent migration and stentfracture. Granulation tissue hyperplasia is the most common complication. Theapplication of metallic airway stent has been limited by these complications.A new idea is given by the success of cardiovascular drug eluting stent. Theproblem of granulation tissue hyperplasia secondary to stent placement may besolved by the use of airway drug eluting stents. Mytomycin C is a kind ofantineoplastic drug. It can also inhibit the hyperplasia of fibroblast. Manyscholars contend that MMC is useful for the management of laryngotracheal stenosis. Airway drug eluting stents, such as dexamethasone eluting covered stentand paclitaxel eluting stent, have been reported, but tracheal MMC eluting drugstent has not been reported. Therefore, we try to make a tracheal MMC elutingstent with nitinol airway stent, PLGA and MMC. PLGA is used as drug carrier.We plan to place the MMC eluting stent in a canine TS model to confirm itsefficacy on reducing granulation tissue hyperplasia.Objective1. To establish a canine TS model by radiofrequency cauterization.2. To prepare tracheal MMC eluting stent and detect its physical and chemicalcharacters.3. To place the MMC eluting stent in canine TS model to confirm the efficacy ofMMC eluting stent in decreasing granulation tissue hyperplasia.Methods1. A model of canine tracheal stenosis induced by radiofrequency cauterizationThe tracheal cartilage ring was injured by radiofrequency at the level of thesixth tracheal ring. A fibrolaryngoscope was used to guide the procedure. Theanimals were observed after operation and examined after euthanasia.Endoscopic and histological examinations were undertaken to evaluate theprogress of stenosis. The degree of stenosis was calculated using the formula:degree of stenosis=(initial lumen area–final lumen area)/initial lumen area×100%.2. The preparation of MMC eluting stentBlended solution containing PLGA and MMC was prepared. Amounts ofdrugs were got from preliminary experiment. The drug eluting stent was preparedby dip coating process. The physical and chemical characters of PLGA-MMCfilm were detected by infrared spectrometer and scanning electron microscope (SEM).3. The efficacy of MMC eluting stent in decreasing the granulation tissuehyperplasia secondary to stent placement16mongrel dogs were randomly divided to3groups including control groupwith naked metallic stent (n=3), control group with PLGA coating stent (n=3) andexperimental group with PLGA-MMC coating stent (n=10). The respective stentswere immediately placed in canine trachea by using a semi-rigid catheter after theestablishment operation of TS model. Fibrolaryngoscope examination wasperformed to observe the degree of TS in every2weeks. The dogs in controlgroups were euthanized after the1st month.1dog in experimental group waseuthanized after a week. After the1st,3th and6th month,3dogs in experimentalgroup were euthanized respectively. After euthanasia, the trachea was excised forgross observation and histological examination. The histological examinationtook place after the sections were stained with HE and Masson. The trachealthickness was measured in the stained sections. SEM examination was performedto observe the epithelium change caused by MMC in experimental group.Results1. A model of canine tracheal stenosis induced by radiofrequency cauterizationTS had developed in all dogs by the21st day post operation. Costalretraction was observed in all dogs after the18th day post operation. At the endof the study, gross and endoscopic examinations showed that stenosis had beeninduced to a satisfactory degree and without any complications. The median ofthe degree of stenosis was93%, with a range of84–94%. Histologicalexamination showed that cartilage was damaged and that granulation tissue andcollagen fibres had formed.2. The preparation of MMC eluting stent The satisfactory MMC eluting stent was prepared by dip coating process.The result of infrared spectrometer indicated that the chemical character of PLGAand MMC in PLGA-MMC film was not changed. The result of SEM showed thatthe nitinol wire was coated PLGA-MMC film closely even after the distortion ofthe stent.3. The efficacy of MMC eluting stent in decreasing the granulation tissuehyperplasia secondary to stent placementAll dogs survived to the end of the study. After the1st month, the resultsshowed that there was no significant difference between the tracheal thicknessand degree of stenosis of the two control groups. The tracheal thickness anddegree of stenosis of the experimental group were less than that of the controlgroups. After the3rd month, both the tracheal thickness and degree of stenosis ofexperimental group were larger than that of the1st month. After the6th month,the TS was relatively stable. The tracheal thickness and degree of stenosis ofexperimental group were larger than that of the3st month. SEM results indicatedthat tracheal epithelium could be injured by the released MMC at the early stage.The impaired tracheal epithelium can be gradually recovered and became normalat the end of the study.Conclusion1. The model of canine tracheal stenosis induced by radiofrequencycauterization is a relatively simple, reliable, and reproducible animal model.This model may be useful in the development of new methods of treatmentfor tracheal stenosis.2. The satisfactory MMC eluting stent can be prepared by dip coating process.3. The MMC eluting stent can release MMC slowly after its placement.Granulation tissue hyperplasia and the degree of TS can be decreased by the released MMC. This study can be the theoretical and practical basis for thefuture study of airway drug stent.