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Skin perfusion and oxygen saturation after mastectomy and radiation therapy in breast cancer patients
Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.ORCID iD: 0000-0002-6804-7708
Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Perimed AB, Järfälla, Stockholm, Sweden.ORCID iD: 0000-0002-3454-6576
Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.ORCID iD: 0000-0002-8027-9632
Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
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2024 (English)In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 75, article id 103704Article in journal (Refereed) Epub ahead of print
Abstract [en]

The pathophysiological mechanism behind complications associated with postmastectomy radiotherapy (PMRT) and subsequent implant-based breast reconstruction are not completely understood. The aim of this study was to examine if there is a relationship between PMRT and microvascular perfusion and saturation in the skin after mastectomy and assess if there is impaired responsiveness to a topically applied vasodilator (Methyl nicotinate - MN). Skin microvascular perfusion and oxygenation >2 years after PMRT were measured using white light diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF) in the irradiated chest wall of 31 women with the contralateral breast as a control. In the non-irradiated breast, the perfusion after application of MN (median 0.84, 25th-75th centile 0.59-1.02 % RBC × mm/s) was higher compared to the irradiated chest wall (median 0.51, 25th-75th centile 0.21-0.68 % RBC × mm/s, p < 0.001). The same phenomenon was noted for saturation (median 91 %, 25th-75th centile 89-94 % compared to 89 % 25th-75th centile 77-93 %, p = 0.001). Eight of the women (26%) had a ≥10 % difference in skin oxygenation between the non-irradiated breast and the irradiated chest wall. These results indicate that late microvascular changes caused by radiotherapy of the chest wall significantly affect skin perfusion and oxygenation.

Place, publisher, year, edition, pages
Elsevier, 2024. Vol. 75, article id 103704
National Category
Cancer and Oncology Surgery
Identifiers
URN: urn:nbn:se:liu:diva-201655DOI: 10.1016/j.breast.2024.103704ISI: 001216488000001PubMedID: 38460441Scopus ID: 2-s2.0-85186992326OAI: oai:DiVA.org:liu-201655DiVA, id: diva2:1845127
Available from: 2024-03-17 Created: 2024-03-17 Last updated: 2024-05-22Bibliographically approved
In thesis
1. Microvascular Function Assessment after Mastectomy and Radiation Therapy in Breast Cancer Patients: From Methodology to Clinical Application
Open this publication in new window or tab >>Microvascular Function Assessment after Mastectomy and Radiation Therapy in Breast Cancer Patients: From Methodology to Clinical Application
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Post-mastectomy radiotherapy (PMRT) is an important part of the treatment of breast cancer. It reduces the risk of recurrence and improves overall survival. Scaring and fibrotization of the skin and subcutaneous tissue of the chest wall or remaining breast are among its side-effects. These late side-effects of PMRT may in turn affect skin microcirculation and oxygenation, although this connection is not completely established. In patients that later require breast reconstruction, it is difficult as a plastic surgeon to evaluate if the microcirculatory changes have been affected by PMRT, and how such effects should have an impact on the choice of reconstructive method. In the work presented in this thesis, laser speckle contrast imaging (LSCI), laser-doppler flowmetry (LDF) and diffuse reflectance spectroscopy (DRS) have been used with a strong vasodilator, methyl nicotinate (MN) to study the microcirculatory changes after PMRT.

In studies I and II, we aimed to find the optimal concentration of MN and its main mechanisms of action. In healthy volunteers, the microvascular response to different concentrations of MN was evaluated on the forearm using LSCI. It was found that a concentration of 20 mmol/l resulted in a quick vasodilatory response with a long plateau phase, minimal tissue edema and no non-responders. In study II, we utilized locally administered drugs to block the three main pathways responsible for skin vasodilation. Subsequently, we provoked the skin with MN and assessed its effect with LSCI. From this study we could conclude that MN’s mechanism of action is largely mediated by prostaglandins and partly by local sensory nerves.

In study III, we examined the skin microcirculatory response in breast cancer patients before, immediately after, and at two and six months following unilateral PMRT, using the contralateral breast as a control. A significant increase in basal skin perfusion and perfusion after application of MN was observed on the irradiated chest wall immediately after RT compared to the contralateral breast and compared to before RT. At six months after RT, there was no longer a difference in basal skin perfusion or after application of MN in the irradiated chest wall compared to the contralateral breast and compared to before RT was given. The results from this study concluded that skin perfusion in the irradiated chest wall had returned to normal when measured six months after RT.

In study IV, the late effects on skin microvascular function were studied in women who had undergone mastectomy and PMRT several years prior to the study. Skin perfusion and oxygen saturation was measured with white light diffuse reflectance spectroscopy (DRS) combined with Laser Doppler Flowmetry (LDF) before and after application of MN on the irradiated chest wall with the contralateral non-irradiated breast as control. In this study we found that skin perfusion and oxygenation in the breast are affected several years after radiotherapy and that our method could be a valuable clinical tool prior to deciding surgical procedures after PMRT.

To conclude, MN can be topically applied to the skin to reliably assess microvascular function and the microvascular capacity. LSCI and LDF have different strengths and drawbacks, with LSCI having the advantage of having a large spatial resolution that allows for measurements of control areas in the same field of view as the provoked areas. LDF in combination with DRS enabled us to further assess perfusion and oxygenation simultaneously which could be an advantage in fibrotic skin where skin perfusion and oxygen saturation may not correlate with each other. Although the study groups differed between the study examining the early effects of PMRT with the late effects of PMRT, we have been able to non-invasively visualize changes in microcirculation in relation to the acute and chronic phase after PMRT. Future studies are needed to investigate the value of pre-operative measurements with MN provocation for predicting surgical outcome.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2024. p. 95
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1911
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-203080 (URN)10.3384/9789180756051 (DOI)9789180756044 (ISBN)9789180756051 (ISBN)
Public defence
2024-05-30, Belladonna, Building 511, Campus US, Linköping, 09:00
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Supervisors
Available from: 2024-04-29 Created: 2024-04-29 Last updated: 2024-04-29Bibliographically approved

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Elawa, SherifFredriksson, IngemarSteinvall, IngridZötterman, JohanFarnebo, SimonDroog Tesselaar, Erik

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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of Hand and Plastic SurgeryDivision of Biomedical EngineeringFaculty of Science & EngineeringDivision of Diagnostics and Specialist MedicineMedical radiation physics
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