Fully covered self-expanding metal stents placed temporarily in the bile duct: safety profile and histologic classification in a porcine model

<p>Abstract</p> <p>Background</p> <p>Fully covered Self-Expanding metal stents (FCSEMS) have been shown efficacious in palliating malignant biliary obstructions. There is little data analyzing mucosal response to their temporary placement in the bile duct.</p> <p>Methods</p> <p>Ten mini pigs underwent endoscopic placement of a FCSEMS (Wallflex, Boston Scientific). FCSEMS were kept in place for three months. At the end of the 3 months, FCSEMS were removed endoscopically. Five pigs were euthanized and their bile ducts harvested. The other five were kept alive for another month post removal. A single pathologist, created a scoring system (to determine degree of inflammation, fibrosis, and epithelial injury), examined all specimens in a blinded fashion.</p> <p>Results</p> <p>Four FCSEMS spontaneously migrated in the duodenum. On post mortem examination, mild mucosal thickness was noted in three bile duct specimens while superficial inflammation of the bile duct was noted in five animals. Histologic examination of the bile duct revealed focal acute inflammation in both groups. For the 5 animals euthanized immediately after stent removal, there was a tendency to have superficial mucosal erosion and fibrosis. In contrast, increased chronic inflammation was more commonly seen in the animals 1 month post stent removal, with all animals in this group showing moderate degrees of mononuclear inflammatory cell mucosal infiltrates. No severe inflammatory or fibrotic duct injury was observed in any of the study animals, with degree of injury graded as mild to moderate.</p> <p>Conclusion</p> <p>FCSEMS appear to induce minimal tissue overgrowth or fibrosis post placement. Ease of removability and no significant histologic injury are advantages noted with FCSEMS., however, further studies are needed to evaluate treating benign biliary strictures with FCSEMS in humans.</p

Intracranial Sonodynamic Therapy With 5-Aminolevulinic Acid and Sodium Fluorescein: Safety Study in a Porcine Model

BackgroundSonodynamic therapy (SDT) is an emerging ultrasound-based treatment modality for malignant gliomas which combines ultrasound with sonosensitizers to produce a localized cytotoxic and modulatory effect. Tumor-specificity of the treatment is achieved by the selective extravasation and accumulation of sonosensitizers in the tumor-bearing regions. The aim of this study is to demonstrate the safety of low-intensity ultrasonic irradiation of healthy brain tissue after the administration of FDA-approved sonosensitizers used for SDT in experimental studies in an in vivo large animal model.MethodsIn vivo safety of fluorescein (Na-Fl)- and 5 aminolevulinic acid (5-ALA)-mediated low-intensity ultrasound irradiation of healthy brain parenchyma was assessed in two sets of four healthy swine brains, using the magnetic resonance imaging (MRI)-guided Insightec ExAblate 4000 220 kHz system. After administration of the sonosensitizers, a wide fronto-parietal craniotomy was performed in pig skulls to allow transmission of ultrasonic beams. Sonication was performed on different spots within the thalamus and periventricular white matter with continuous thermal monitoring. Sonication-related effects were investigated with MRI and histological analysis.ResultsPost-treatment MRI images acquired within one hour following the last sonication, on day one, and day seven did not visualize any sign of brain damage. On histopathology, no signs of necrosis or apoptosis attributable to the ultrasonic treatments were shown in target areas.ConclusionsThe results of the present study suggest that either Na-FL or 5-ALA-mediated sonodynamic therapies under MRI-guidance with the current acoustic parameters are safe towards healthy brain tissue in a large in vivo model. These results further support growing interest in clinical translation of sonodynamic therapy for intracranial gliomas and other brain tumors

Endoscopic Ultrasound-Guided Radiofrequency Ablation (EUS-RFA) of the Pancreas in a Porcine Model

Backgrounds. Limited effective palliative treatments exist for pancreatic cancer which includes surgery or chemotherapy. Radiofrequency ablation (RFA) uses high frequency alternating current to ablate diseased tissue and has been used to treat various tumors. In this study, we evaluated a prototype probe adjusted to the EUS-needle to perform EUS-RFA to permit coagulative necrosis in the pancreas. Methods. Five Yucatan pigs underwent EUS-guided radiofrequency ablation of the head of their pancreas. Using an EUS-needle, RFA was applied with 6 mm and then 10 mm of the probe exposed at specific wattage for preset durations. Results. Only one pig showed moderate levels of pancreatitis (20% proximal pancreatitis). The other animals showed much lower areas of tissue damage. In 3 of the 5 pigs, the proximal pancreas showed greater levels of tissue injury than the distal pancreas, consistent with the proximity of the tissue to the procedure site. In 1 pig, both proximal and distal pancreas showed minimal pancreatitis (1%). There was minimal evidence of fat necrosis in intra-pancreatic and/or extra-pancreatic adipose tissue. Conclusion. EUS-guided RFA of the pancreatic head with the monopolar probe through a 19-gauge needle was well tolerated in 5 Yucatan pigs and with minimal amount of pancreatitis