Abstract

To evaluate dynamic tissue changes after airway stenting (AS) with a newly designed metal brachytherapy stent (BS) loaded with radioactive 125I seeds in normal rabbits. Forty-five normal New Zealand white rabbits were divided into 3 groups (groupA: stent without seeds; groupB: stent with 0.4mCi active seeds; groupC: stent with 0.8mCi active seeds) and underwent AS under C-arm guidance. Then, five rabbits were killed from each group at 2, 4, and 8weeks for further examination. Laboratory tests (including routine blood tests, liver function, kidney function, and electrolytes), gross observations, and tissue changes of Masson/hematoxylin-eosin staining, plus immunohistochemistry of α-SMA, NOX4, and TGF-β were performed at each time point. All animals underwent AS successfully without procedure-related death, but one animal died at 6weeks due to severe pulmonary infection in groupC. Apart from a transient increase in white blood cells (P < 0.05) and a gradual increase in ROS levels (P < 0.05), other blood test items showed no significant changes (P > 0.05). The brachytherapy injury score increased with irradiation dose accumulation (P < 0.05), but tissue hyperplasia at the stent end in groupC was less severe than that in groupsA and B (P < 0.05). Airway lateral fibrosis was observed in all groups by histopathologic analysis; however, fibrosis in groupC was more severe than that in groupsA and B (P < 0.05). The brachytherapy injury score increased with irradiation dose accumulation, while granulation tissue hyperplasia at the stent end was inhibited by 125I brachytherapy within 8weeks.

Highlights

  • The brachytherapy injury score increased with irradiation dose accumulation (P < 0.05), but tissue hyperplasia at the stent end in Group C was less severe than that in Groups A and B (P < 0.05)

  • The brachytherapy injury score increased with irradiation dose accumulation, while granulation tissue hyperplasia at the stent end was inhibited by 125I brachytherapy within 8 weeks

  • Airway stenting (AS) is an important strategy to alleviate severe dyspnea caused by malignant tracheal stenosis; the proliferation of tumors or granulation tissue often leads to stent restenosis, with an incidence of 5–45% within 3 months[1,2]

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Summary

Introduction

Airway stenting (AS) is an important strategy to alleviate severe dyspnea caused by malignant tracheal stenosis; the proliferation of tumors or granulation tissue often leads to stent restenosis, with an incidence of 5–45% within 3 months[1,2]. It is well known that external beam radiotherapy (EBRT) can significantly inhibit stent intimal hyperplasia and tumor growth, but 40% of patients cannot tolerate the associated complications. 125I seed brachytherapy is an effective local regimen to inhibit normal cell proliferation and malignant tumors to a certain extent to prevent excessive proliferation of granulation tissue and has been applied to solid tumor treatment for many years, such prostate cancer[4], lung cancer[5], liver cancer[6], and bone metastasis[7]. To solve the above problems, Chinese scholars have combined radioactive 125I seeds with conventional metal airway stents to form a brachytherapy stent (BS) inspired by esophageal 125I brachytherapy stents[8] and biliary 125I brachytherapy stents[9], which have been reported in a previous clinical study. This study seeks to understand the effects of BS on the tracheal wall of normal rabbits to provide a theoretical basis for the development of new-generation stents in the future

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