| Background:Esophageal cancer is one of the most malignant tumors all over the world, and increasing rapidly in incidence. Because of its low early diagnosis rate, most patients appeared the symptoms of difficulty swallowing due to malignant obstruction. Thus, patients tend to have a poor prognosis and short survival. As one of the non-operative management, metallic stent insertion is widely used because this technique is much less invasive, prolongs survival, shortens hospital stay, and improves quality of life. However, conventional self-expanding metallic stents (SEMSs) can only facilitate the palliative relief but have no antitumor effect. And re-occlusion after SEMS insertion occurs over time resulting from tumor ingrowth, tumor overgrowth and tissue hyperplasia as a consequence of chronic irritation, especially in the two ends of the stents. In recent years, the use of drug-eluting stents has become a promising approach in the treatment of stenosis in coronary and peripheral arteries. According to our speculation, it may have the similar effect of the stent covered with polyurethane containing10%(wt/vol) paclitaxel in the digestive system.Objective:1. To assess the anesthetic effect of ketamine combining promethazine, pentobarbital sodium and chloral hydrate;2. To establish the rabbit esophageal squamous carcinoma model with the endoscopic method;3. To evaluate the safety and efficiency of the self-expanding metallic stents insertion to the rabbit esophagus;4. To evaluate the safety and efficiency of the paclitaxel-eluting metallic stent (PEMS) for the rabbit esophageal squamous carcinoma;5. To evaluate the local pathological change of esophageal tissue after the insertion of PEMS.Methods:1. Total of180healthy New Zealand white rabbits (Bought form the farm of Qinglongshan, Jiangning, Nanjing, certificate NO. SCXK2007-2008) were used,3months old, with the random gender, weight of1.8-2.5kg, fed by the normal food and randomly enrolled into3groups. One day before the operation, animals were fast. Then,0.5ml/kg3.3%ketamine (2ml:0.1g, NO1, South chendong road, Gutian, Fujian, certificate NO.10531) combining0.8%promethazinea(lml:25mg, Fengnuo limited company, certificate NO.101205),45mg/kg3%pentobarbital sodium (BIOCAM, certificate NO.57330, content99.03%) and5ml/kg10%chloral hydrate (Chemical reagent co., LTD, certificate NO.20120720, content99.5%) were intraperitoneal injected into the animals, respectively. Meanwhile, breathing and heart rate, corneal reflex, anesthesia induction time, anesthesia time and death rate were recorded.2. Proliferation of tumor cells:Rabbit VX2(tumor cell originating from the rabbit squamous epithelium) tumor block was injected into the muscular layer of the hind legs. After about2weeks, tumor block grows to a VX2tumor mass. And then, the mass was sterilely shredded into little fragments and stored at minus80degrees. 3. Injection of tumor fragments into rabbit esophagus:Using the endoscopic methods for rabbit model establishment:Resurrecting the VX2fragments, cutting it to about lmm size, injecting the VX2fragments into the esophageal submucosal layer by the ultra-slim endoscope. In the follow-up, esophageal endoscopy was performed weekly.4. The established rabbit models were randomly enrolled two groups, PEMS and SEMS group, respectively. When over2/3obstruction was revealed using ultra-slim endoscope or the choledochoscope which meets the indication of stent therapy, stent insertion was performed into the diseased lesion using the introducer set.5. Postoperative observation:Esophageal endoscopy was performed weekly, revealing the re-obstruction, migration and other adverse events.Rabbits were executed2weeks after stent insertion during which the safety and efficiency of PEMSs and SEMSs at the endoscopic, macro and micro level.Results:1. The death rate was16.7%in ketamine combining promethazine group,3.3%in pentobarbital sodium group and0.0%in chloral hydrate group, respectively (P<0.05). Using the pairwise comparison, the death rate was significantly different between the ketamine group and it in the pentobarbital or chloral hydrate group, but was similar between the pentobarbital and chloral hydrate group. Satisfactory anesthesia rate in the survived rabbits was84.0%in ketamine group,86.2%in pentobarbital sodium group and96.7%in chloral hydrate group, respectively (P≤0.001). Using the pairwise comparison, the satisfactory anesthesia rate was significantly different between the chloral hydrate group and it in the pentobarbital or ketamine group, but was similar between the pentobarbital and ketamine group.2. In this study, the VX2tumor formation rate was high by injecting the fragments into the leg muscular and esophageal submucosa, with the low early metastasis rate, tendency of tumor endoluminal growth, no infiltration to the serosa or surrounding organs before stent insertion.3. During or after the stent placement,4migration,2anesthetic accident,1death since the irregular procedure and1tumor infiltration occurred. Besides, there was no bleeding, perforation or other adverse events. The total adverse event rate had no significant difference between the two groups.4. A total of30rabbit model received the stent insertion and data of22rabbits was included in the study. The tumor volume was7.00±4.30cm3in the PEMS group and0.94±1.51cm3in the SEMS group, respectively (P<0.05). The esophageal wall defect was0.70±0.63cm2in the PEMS group and0.17±0.16cm2in the SEMS group, respectively (P<0.05). The area of tumor under EUS was4.40±1.47cm2in the PEMS group and1.30±1.06cm2(P<0.05). Other indices were not significantly different between the two groups.Conclusions:1. By comparing the three kinds of anesthesia, the results showed that the death rate was dominantly low in the pentobarbital or chloral hydrate group. However, the satisfactory anesthesia rate was high in the chloral hydrate group than that in pentobarbital group. Thus, the chloral hydrate could be a safe and effective drug in rabbit anesthesia.2. The tumor tends to grow to the esophageal luman after the submucosal injection of VX2tumor fragments, with low rate of early surrounding tissue infiltration and metastasis. VX2rabbit esophageal squamous carcinoma model is an optimal model for the research of advanced esophageal carcinoma.3. The adverse event rate during or after the stent insertion was low. Besides, the adverse events associated with the stent only included the migration but no bleeding or perforation. Therefore, SEMS insertion into rabbit esophagus was safe.4. After insertion of PEMS or SEMS, the total adverse event rate had no significant difference between the two groups. However, the tumor size was much smaller in the PEMS group than that in the SEMS group when executing the rabbits. Thus, the PEMS is safe and effective which may slow the tumor growth. |
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