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溶组织梭菌胶原酶在放射性囊状挛缩治疗中的应用。

The Collagenase of the Bacterium Clostridium histolyticum in the Treatment of Irradiation-Induced Capsular Contracture.

机构信息

Department of Hand-, Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwig-Guttmann-Strasse 13, 67071, Ludwigshafen, Germany.

Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, 02115, USA.

出版信息

Aesthetic Plast Surg. 2019 Jun;43(3):836-844. doi: 10.1007/s00266-018-1267-y. Epub 2018 Nov 19.

DOI:10.1007/s00266-018-1267-y
PMID:30456640
Abstract

BACKGROUND

Irradiation therapy is an important pillar in the treatment of breast cancer. However, it can trigger capsular fibrosis, the most significant complication of implant-based breast reconstruction. As collagen is the main component of fibrotic capsules, the collagenase of the bacterium Clostridium histolyticum poses a potential treatment option for this pathological condition.

METHODS

Thirty-six rats received miniature silicone implants on their backs. On day 1, the implant sites of two groups were irradiated with 10 Gy. On day 120, one irradiated group received collagenase injections into the implant pockets (n = 12). Non-irradiated (n = 12) and irradiated capsules (n = 12) were injected with plain solvent solution serving as controls. Data were analyzed by means of in vivo imaging, histology, immunohistochemistry and gene expression analysis.

RESULTS

Compared with both controls, the injection of collagenase led to significantly thinner capsules. This was verified by in vivo imaging and histology. Although irradiation provoked alterations in capsule collagen structure and vessel wall thickness, the application of collagenase resulted in a significant reduction of collagen density. This was accompanied by an up-regulation of VEGF-A gene expression. Of note, hematoma formation inside the implant pocket occurred in two cases after collagenase injection.

CONCLUSIONS

The collagenase of the bacterium Clostridium histolyticum is effective in degrading irradiation-induced capsular fibrosis around silicone implants. Hematoma formation occurred most likely because of irradiation-induced alterations in vessel wall architecture and capsule vascularization. Further studies need to be performed to address the clinical safety of this novel treatment option.

摘要

背景

放射治疗是乳腺癌治疗的重要支柱。然而,它会引发包膜纤维化,这是植入物乳房重建的最主要并发症。由于胶原蛋白是纤维囊的主要成分,溶组织梭菌的胶原酶为这种病理状况提供了一种潜在的治疗选择。

方法

36 只大鼠背部接受微型硅胶植入物。第 1 天,两组动物的植入部位接受 10 Gy 的照射。第 120 天,一组照射组将胶原酶注入植入物囊中(n = 12)。未照射组(n = 12)和照射组(n = 12)注入普通溶剂溶液作为对照。通过体内成像、组织学、免疫组织化学和基因表达分析来分析数据。

结果

与两个对照组相比,胶原酶的注射导致囊明显变薄。这通过体内成像和组织学得到证实。尽管照射引起了囊胶原结构和血管壁厚度的改变,但胶原酶的应用导致胶原密度显著降低。这伴随着 VEGF-A 基因表达的上调。值得注意的是,胶原酶注射后有两例在植入物囊中出现血肿形成。

结论

溶组织梭菌的胶原酶在降解硅胶植入物周围的照射诱导的囊纤维化方面是有效的。血肿的形成很可能是由于照射引起的血管壁结构和囊血管化的改变。需要进一步研究来解决这种新的治疗选择的临床安全性问题。

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The collagenase of the bacterium Clostridium histolyticum does not favor metastasis of breast cancer.溶组织梭菌胶原酶并不促进乳腺癌转移。
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Comment on: "The Treatment of Capsular Contracture Around Breast Implants Induced by Fractionated Irradiation: The Collagenase of the Bacterium Clostridium Histolyticum as a Novel Therapeutic Approach".对《分次照射诱导的乳房植入物周围包膜挛缩的治疗:溶组织梭状芽孢杆菌胶原酶作为一种新的治疗方法》的评论
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Invited Response on: "Comment on: "The Treatment of Capsular Contracture Around Breast Implants Induced by Fractionated Irradiation: The Collagenase of the Bacterium Clostridium Histolyticum as a Novel Therapeutic Approach".
Aesthetic Plast Surg. 2021 Oct;45(5):2525-2526. doi: 10.1007/s00266-021-02286-4. Epub 2021 Apr 14.

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