Sebastian Fischer1,2, Yannick Diehm3,4, Thomas Henzler5, Martin R Berger6, Jonas Kolbenschlag7, Anne Latz3, Ericka M Bueno3, Christoph Hirche4, Ulrich Kneser4, Bohdan Pomahac3. 1. Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA, 02115, USA. sfischer4@partners.org. 2. Department of Hand-Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwig-Guttmann-Strasse 13, 67071, Ludwigshafen, Germany. sfischer4@partners.org. 3. Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA, 02115, USA. 4. Department of Hand-Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwig-Guttmann-Strasse 13, 67071, Ludwigshafen, Germany. 5. Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim-Heidelberg University, Theodor-Kutzer Ufer 1-3, 68167, Mannheim, Germany. 6. German Cancer Research Center (DKFZ), Toxicology and Chemotherapy Unit, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. 7. Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, Martin-Luther Hospital, Caspar-Theyß-Straße 27-31, 14193, Berlin, Germany.
Abstract
BACKGROUND: Capsular contracture remains the most frequent long-term complication after augmentation mammoplasty with silicone implants. Thereby, the main part of the fibrotic capsule is collagen. The collagenase of the bacterium Clostridium histolyticum is approved for the treatment of fibrotic diseases and has been demonstrated to be effective for capsular fibrosis treatment in the short term. However, long-term effectiveness is currently unknown but mandatory for clinical utilization. MATERIALS AND METHODS: Forty-eight rats received miniature silicone implants and an injection with either collagenase (treatment group) or plain solvent solution (control group) 120 days post insertion. Ten and 60 days after the injections, the rats underwent 7-Tesla magnetic resonance imaging (MRI) and high-resolution ultrasound (HR-US). Capsule tissue was harvested, and capsule thickness and collagen density were evaluated through histology. Furthermore, the expression levels of inflammatory (CD68, IL4, IL10, IL12, IL13), pro-, and anti-fibrotic (TGFb1, TGFb3, Smad3, Col1-4) genes were analyzed using qRT-PCR. RESULTS: On days 10 and 60 after injection of collagenase, histology showed that capsule thickness was significantly reduced in the treatment group when compared with the control (p < 0.05). Thickness measurements were verified by MRI and HR-US analysis. Skin perforation occurred in two cases after collagenase injection. The initial up-regulation of pro-fibrotic and inflammatory genes 10 days after collagenase injection did not persist in the long term. Contrarily, on day 60, a slight trend towards lower expression levels with a significant down-regulation of TGFb3 was detected in the treatment group. CONCLUSION: The collagenase of the bacterium C. histolyticum effectively degrades capsular fibrosis around silicone implants with stable outcomes throughout 60 days post injection. Skin perforation and adequate and uniform drug distribution within the implant pocket are issues that need to be addressed. Further studies are warranted to clarify whether collagenase injections have the potential to become a viable treatment option for capsular contracture. NO LEVEL ASSIGNED: This journal requires that authors 46 assign a level of evidence to each article. For a full 47 description of these Evidence-Based Medicine ratings, 48 please refer to the Table of Contents or the online 49 Instructions to Authors. www.springer.com/00266 .
BACKGROUND: Capsular contracture remains the most frequent long-term complication after augmentation mammoplasty with silicone implants. Thereby, the main part of the fibrotic capsule is collagen. The collagenase of the bacterium Clostridium histolyticum is approved for the treatment of fibrotic diseases and has been demonstrated to be effective for capsular fibrosis treatment in the short term. However, long-term effectiveness is currently unknown but mandatory for clinical utilization. MATERIALS AND METHODS: Forty-eight rats received miniature silicone implants and an injection with either collagenase (treatment group) or plain solvent solution (control group) 120 days post insertion. Ten and 60 days after the injections, the rats underwent 7-Tesla magnetic resonance imaging (MRI) and high-resolution ultrasound (HR-US). Capsule tissue was harvested, and capsule thickness and collagen density were evaluated through histology. Furthermore, the expression levels of inflammatory (CD68, IL4, IL10, IL12, IL13), pro-, and anti-fibrotic (TGFb1, TGFb3, Smad3, Col1-4) genes were analyzed using qRT-PCR. RESULTS: On days 10 and 60 after injection of collagenase, histology showed that capsule thickness was significantly reduced in the treatment group when compared with the control (p < 0.05). Thickness measurements were verified by MRI and HR-US analysis. Skin perforation occurred in two cases after collagenase injection. The initial up-regulation of pro-fibrotic and inflammatory genes 10 days after collagenase injection did not persist in the long term. Contrarily, on day 60, a slight trend towards lower expression levels with a significant down-regulation of TGFb3 was detected in the treatment group. CONCLUSION: The collagenase of the bacterium C. histolyticum effectively degrades capsular fibrosis around silicone implants with stable outcomes throughout 60 days post injection. Skin perforation and adequate and uniform drug distribution within the implant pocket are issues that need to be addressed. Further studies are warranted to clarify whether collagenase injections have the potential to become a viable treatment option for capsular contracture. NO LEVEL ASSIGNED: This journal requires that authors 46 assign a level of evidence to each article. For a full 47 description of these Evidence-Based Medicine ratings, 48 please refer to the Table of Contents or the online 49 Instructions to Authors. www.springer.com/00266 .
Authors: Yannick Fabian Diehm; Katharina Marstaller; Anna-Maria Seckler; Martin Reinhold Berger; Michael Zepp; Matthias Martin Gaida; Julia Thomé; Dimitra Kotsougiani-Fischer; Ulrich Kneser; Sebastian Fischer Journal: Breast Cancer Date: 2022-02-07 Impact factor: 4.239
Authors: Yannick F Diehm; Dimitra Kotsougiani-Fischer; Elena Porst; Valentin Haug; Laura C Siegwart; Daniel Overhoff; Ulrich Kneser; Sebastian Fischer Journal: PLoS One Date: 2022-07-06 Impact factor: 3.752
Authors: Denis V Krakhotkin; David J Ralph; Gideon A Blecher; Volodymyr A Chernylovskyi; Francesco Greco; Evgeny E Bakurov; Ruslan A Bugaev Journal: Asian J Androl Date: 2021 Mar-Apr Impact factor: 3.285