Optimizing Breast Reconstruction After Mastectomy University of Antwerp Faculty of Medicine and Health Sciences

piiigbes eosrcinatrmsetm Filip Thiessen Optimizing breast reconstruction after mastectomy University of Antwerp Faculty of Medicine and Health Sciences

Optimizing breast reconstruction after mastectomy The use of dynamic infrared thermography

Filip THIESSEN

2020

Antwerp, 2020 Thesis submitted in fulfilment of Promoters: Prof. dr. Wiebren Tjalma the requirements for the degree of Prof. dr. Gunther Steenackers Doctor in Medical Sciences at the Prof. dr. Guy Hubens University of Antwerp Co-promoter: Prof. dr. Veronique Verhoeven

University of Antwerp Faculty of Medicine and Health Sciences

Optimizing breast reconstruction after mastectomy: The use of dynamic infrared thermography

Optimaliseren van borstreconstructies na mastectomie: Het gebruik van dynamic infrared thermography

Thesis submitted in fulfilment of the requirements for the degree of Doctor in Medical Sciences at the University of Antwerp to be defended by Filip THIESSEN Proefschrift voorgelegd tot het behalen van de graad van doctor in de Medische Wetenschappen aan de Universiteit Antwerpen te verdedigen door

Antwerpen, 2020 Promotoren: Prof. dr. Wiebren Tjalma Prof. dr. Gunther Steenackers Prof. dr. Guy Hubens Begeleider: Prof. dr. Veronique Verhoeven Promotoren Prof. dr. Wiebren Tjalma Prof. dr. Gunther Steenackers Prof. dr. Guy Hubens Begeleider Prof. dr. Veronique Verhoeven Members of the jury Internal Prof. dr. Jeroen Hendriks Prof. dr. Manon Huizing Prof. dr. Wiebren Tjalma Prof. dr. Gunther Steenackers Prof. dr. Guy Hubens External Prof. dr. Emiel Rutgers Prof. dr. Assaf Zeltzer

© Filip Thiessen Optimizing breast reconstruction after mastectomy: The use of dynamic infrared thermography / Filip Thiessen Faculteit Geneeskunde, Universiteit Antwerpen, Antwerpen 2020 Thesis Universiteit Antwerpen – with summary in Dutch

Lay-out and cover : Dirk De Weerdt (www.ddwdesign.be) Cover figure: Cold challenge to bilateral DIEP in skin sparing mastectomy (top), rapid and overall rewarming of the skin islands of the DIEP flap (bottom). Table of contents

List of abbreviations 5 General introduction 7 Aims and outline 17

Chapter 1. Breast reconstruction 21 Part A: Breast reconstruction after breast conservation therapy for breast cancer 23 Part B: Breast reconstruction after mastectomy 37

Chapter 2. The evolution of breast reconstructions with free flaps: a historical overview 51

Chapter 3. Dynamic infrared thermography (DIRT) in DIEP flap breast reconstruction: a review of the literature 71

Chapter 4. Dynamic infrared thermography (DIRT) in DIEP flap breast reconstruction: standardization of the measurement set-up 91

Chapter 5. Dynamic infrared thermography (DIRT): clinical studies 105 Part A: DIEP flap breast reconstructions: thermographic assistance as a possibility for perforator mapping and improvement of DIEP flap quality 107 Part B: Dynamic infrared thermography (DIRT) in DIEP flap breast reconstruction: a clinical study with a standardized measurement setup 131 General discussion 149 Summary 161 Samenvatting 165 Curriculum vitae 169 Dankwoord 181

A detailed table of contents is given at the start of each chapter

List of abbreviations

ADM: Acellular Dermal Matrix ALT: Antero Lateral Thigh flap BCT: Breast Conserving/Conservation Therapy CDU: Colour Doppler Ultrasound CTA: Computed Tomography Angiography DCIA: Deep Circumflex Iliac Artery flap DCIS: Ductal carcinoma in situ DIEaP/DIEP: Deep Inferior Epigastric artery Perforator flap DIRT: Dynamic Infrared Thermography DUG: Diagonal Upper Gracilis flap FCI: Fasciocutaneous Infragluteal flap HP: High Profile ICG: Indo-Cyanine Green IGAP: Inferior Gluteal Artery Perforator flap IR: InfraRed IV: Intravenous LAP: Lumbar Artery Perforator flap LD: Latissimus Dorsi flap LICAP: Lateral Intercostal Artery Perforator flap LTP: Lateral Thigh Perforator flap MP: Moderate Profile MRA: Magnetic Resonance Angiography MRI: Magnetic Resonance Imaging MS-TRAM: Muscle Sparing Transverse Rectus Abdominis Myocutaneous flap NSM: Nipple Sparing Mastectomy NNSM: Non Nipple Sparing Mastectomy PAP: Profunda Artery Perforator flap PFAP: Profunda Femoris Artery Perforator flap PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analysis QOL: Quality of Life SGAP: Superior Gluteal Artery Perforator flap SIEA: Superficial Inferior Epigastric Artery flap TDAP: Thoracodorsal Artery Perforator flap (Sc-)TFL: (Septocutaneous) Tensor Fascia Lata flap TMG: Transverse Myocutaneous Gracilis flap TRAM: Transverse Rectus Abdominis Myocutaneous flap TUG: Transverse Upper Gracilis flap VUG: Vertical Upper Gracilis flap

General introduction

Contents

Breast cancer 9 Breast cancer reconstruction 9 Dynamic infrared thermography 11 References 15 Aims 18 Outline 19 References 20

General introduction

Breast cancer

reast cancer is the most common cancer in women worldwide with more than two million new cases in 2018 [1]. The country with the highest incidence rates of breast cancer in the world is Belgium with age-standardized cancer index of 113.2 per B100.000 females, which totals to around 11,000 women each year [2].

Breast cancer reconstruction

The treatment of breast cancer often involves a mastectomy as part of the therapy. One out of 7 patients undergoes a breast reconstruction after mastectomy. Half of which are performed with autologous tissue. Thirty- two percent of the autologous tissue flaps are Deep Inferior Epigastric Perforator (DIEP)-flaps [3]. Reconstruction following mastectomy offers women an opportunity to soften some of the emotional and aesthetic effects of this disease. Autologous tissue breast reconstruction remains the technique associated with the highest patient satisfaction and represents preferred technique for recreation of the breast [4, 5]. Breast reconstructions with perforator flaps from the lower abdomen, Deep Inferior Epigas- tric artery Perforator flap (DIEP-flap), have become the gold standard for autologous breast reconstruction after breast amputation. The abdominal donor site remains unmatched in breast reconstruction for its volume, color and texture resemblance with native breast tissue and for its potency to match a ptotic opposite breast that tends to age in a natural fashion [6, 7]. The skin and subcutaneous tissue from the patient’s lower abdomen are transplanted as a free flap to the thorax to reconstruct the patient’s breast. The flap is perfused from the deep inferior epigastric artery and one or two concomitant veins through a perforator. In DIEP-flap breast reconstruction, the blood supply to the flap is re-established by anastomosing the deep inferior epigastric artery and vein to the internal mammary artery and vein. (Figure 0.1)

9 General introduction

The selected perforator is the only source of blood supply to the flap. Selection of the best perforators is of uttermost importance in this procedure. This will reduce operative time, lower complication rates and ensure an overall better result. There are a number of methods of locating perforating vessels in the flap, such as Computer Tomography Angiography (CTA), Color Doppler ultrasound (CDU), Magnetic resonance Angiography (MRA) or Dynamic Infrared Thermography (DIRT) [8, 9]. The current gold standard for perforator selection is CTA. on which the location and hemodynamic properties of the flap can be reviewed [8, 10]. In order to be considered ideal in clinical conditions, a method should meet the following conditions: non-invasive, simple, repeatable, intra-operative assessment and low cost. DIRT can be an alternative. DIRT uses an Infrared (IR) camera to measure the skin temperature based on heat emitted by tissues. This generates a color-coded map, which is a translation for the skin perfusion.

Figure 0.1. Schematic drawing of DIEP flap (credits KS).

10 General introduction

Dynamic infrared thermography

The human body tries to maintain a constant temperature that is different from the surroundings. This is possible thanks to an equilibrium of all systems within the human body, which leads to dynamic changes in heat emission. The heat is transported through the body by the circulat- ing blood. Heat loss from the skin to the environment is possible by conduction, convection, evaporation and radiation (Figure 0.2). The principal mechanism under stable conditions (18°C to 25°C) to achieve an equilibrium is radiative heat loss from the skin to the environment. This radiative heat loss takes places in the form of infrared (IR) radiation [11, 12]. In medical IR thermography the body surface temperature is measured with the use of an IR camera. Colour-coded maps are created that visualize the vascular perfusion of the skin (Figure 0.3). In most cases, a rainbow

Figure 0.2. Heat loss adapted from De Weerd et al.[11].

11 General introduction

palette is used for infrared-thermography [11]. Despite its popularity these colored maps have not shown to be superior to the grayscale map due to the fact that the human visual system is more sensitive to changes in luminance [13]. Studies have shown a good correlation between skin temperature and skin perfusion. Measurement of skin temperature can therefore provide information of skin perfusion [11, 14]. Already in the 1950’s IR thermography was used as medical diagnostic tool in breast cancer [15]. Due to the low sensitivity of the early cameras

Figure 0.3. In medical IR thermography the body surface temperature is measured with the use of an IR camera. Colour-coded maps are created that visualize the vascular perfusion of the skin. Before microsurgical anastomosis: flap is cold due to ischemia (top of image, circle around flap); after microvascular anastomosis: rapid and progressive rewarming: circle around zone of rewarming (bottom of image).

12 General introduction

the technique was unsuitable for detecting subtle temperature changes. In the last years, thermography has gained in popularity due to considerable improvements of the sensitivity of infrared-cameras. Studies so far indicate that IRT can be successfully used in different medical fields such as senol- ogy (breast cancer diagnosis), endocrinology (diabetic neuropathy) and dermatology (skin cancer diagnosis) [16]. During the COVID-19 pandemic thermography is commonly used at the entrance of hospitals and other public places to detect people with elevated body temperature (Figure 0.4) [17].

Figure 0.4. Use of IR thermography at entrance of University Hospital Antwerp during COVID-19 pandemic.

13 General introduction

IR thermography can be used as a static or dynamic examination. A single image is taken in static IR thermography, resulting in vague and unclear images. Dynamic IR thermography (DIRT) uses a thermal challenge to rule out interference from vascular patterns in the human body and measures the rate and pattern of rewarming after this challenge. The thermal stress can be achieved by cold or hot stress. This technique allows to identify the most dominant perforators and the area they perfuse. The use of DIRT in breast reconstruction with a DIEP flap can provide the surgeon with valuable information in the preoperative, peroperative and postoperative phases [11, 18-21].

14 General introduction

References

1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424. 2. World Cancer Research Fund AifCR. Breast Cancer statistics. 2019. 3. KCE. Borstreconstructie na kanker in drie cijfers. 2019. 4. Macadam SA, Bovill ES, Buchel EW, Lennox PA. Evidence-Based Medicine: Autologous Breast Reconstruction. Plast Reconstr Surg. 2017;139:204e-29e. 5. Serletti JM, Fosnot J, Nelson JA, Disa JJ, Bucky LP. Breast reconstruction after breast cancer. Plast Reconstr Surg. 2011;127:124e-35e. 6. Blondeel PN. One hundred free DIEP flap breast reconstructions: a personal experience. Br J Plast Surg. 1999;52:104-11. 7. Healy C, Allen RJ, Sr. The evolution of perforator flap breast reconstruction: twenty years after the first DIEP flap. J Reconstr Microsurg. 2014;30:121-5. 8. Mohan AT, Saint-Cyr M. Advances in imaging technologies for planning breast reconstruction. Gland Surg. 2016;5:242-54. 9. Nahabedian MY. Overview of perforator imaging and flap perfusion technologies. Clin Plast Surg. 2011;38:165-74. 10. Rozen WM, Garcia-Tutor E, Alonso-Burgos A, Acosta R, Stillaert F, Zubieta JL, et al. Planning and optimising DIEP flaps with virtual surgery: the Navarra experience. J Plast Reconstr Aesthet Surg. 2010;63:289-97. 11. de Weerd L, Mercer JB, Weum S. Dynamic infrared thermography. Clin Plast Surg. 2011;38:277- 92. 12. Jiang LJ, Ng EY, Yeo AC, Wu S, Pan F, Yau WY, et al. A perspective on medical infrared imaging. J Med Eng Technol. 2005;29:257-67. 13. Bolrand d, Taylor II R. Rainbow color map (still) considered harmful. IEE computer graphics and Applications 2007;27. 14. Awwad AM, White RJ, Webster MH, Vance JP. The effect of temperature on blood flow in island and free skin flaps: an experimental study. Br J Plast Surg. 1983;36:373-82. 15. Lawson R. Implications of surface temperatures in the diagnosis of breast cancer. Can Med As- soc J. 1956;75:309-11. 16. Lahiri BB, Bagavathiappan S, Jayakumar T, Philip J. Medical applications of infrared thermography: A review. Infrared Phys Technol. 2012;55:221-35. 17. Enforcement Policy for Telethermographic Systems During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency Guidance for Industry and Food and Drug Administration Staff. 2020. https://www.fda.gov/media/137079/download 18. de Weerd L, Mercer JB, Setsa LB. Intraoperative dynamic infrared thermography and free-flap surgery. Ann Plast Surg. 2006;57:279-84.

15 General introduction

19. de Weerd L, Weum S, Mercer JB. The value of dynamic infrared thermography (DIRT. in perfora- torselection and planning of free DIEP flaps. Ann Plast Surg. 2009;63:274-9. 20. Thiessen FEF, Tondu T, Cloostermans B, Dirkx YAL, Auman D, Cox S, et al. Dynamic InfraRed Thermography (DIRT) in DIEP-flap breast reconstruction: A review of the literature. Eur J Obstet Gynecol Reprod Biol. 2019;242:47-55. 21. Hennessy O, Potter SM. Use of infrared thermography for the assessment of free flap perforators in autologous breast reconstruction: A systematic review. JPRAS Open. 2020;23:60-70.

16 Aims and outline

Contents

Aims 18 Outline 19 References 20 General introduction

Aims

s a plastic and reconstructive surgeon I am member of the multidisciplinary breast clinic and responsible for breast reconstructions after breast cancer treatment and prophylactic mastectomies. Reconstruction following mastectomy offers Awomen an opportunity to mollify some of the emotional and aesthetic effects of this disease. Autologous breast-reconstruction remains the technique associated with the highest patient satisfaction and represents the preferred technique for recreation of the breast after mastectomy [1, 2]. Reconstructions with Deep Inferior Epigastric artery Perforator (DIEP) flaps have become the gold standard for autologous breast reconstruction in our department as in many other departments [3-5]. Selection of the best perforator is of uttermost importance in this procedure, as it is the only source of blood supply to the flap. Computed Tomography Angiography (CTA) is the gold standard nowadays for selection of the perforators [6, 7]. Not only the selection of the perforators is mandatory for successful breast reconstructions with free flaps. Flap failure in breast-reconstructions is often due to technical failures during the dissection of the perforator, failure of the anastomosis or due to kinking or compression of the pedicle during flap-inset and shaping. Clinical monitoring is mostly used to diagnose these problems [8]. In this doctoral thesis we give an overview of common used techniques in breast reconstructions and the evolution of free flap reconstructions in time. We give an overview of the use of dynamic infrared thermography (DIRT) during breast reconstructions and we evaluate and improve the use of DIRT with our new standardized measurement set-up during all phases of breast reconstructions with free flaps.

18 General introduction

Outline

Chapter 1 provides an overview of the types of breast reconstructions that are performed after breast conserving therapy (BCT) and after mastectomy.

Reconstructive breast surgery aims to recreate a natural looking breast that is warm, soft and feels natural. Breast reconstruction with autologous free flaps matches these expectations. Chapter 2 provides a historical overview of the evolution of breast reconstructions with free flaps.

In Chapter 3 we perform a systematic review of the literature between January 1998 and November 23th 2018 to evaluate the use of Dynamic InfraRed Thermography (DIRT) during breast reconstructions with Deep In- ferior Epigastric artery Perforator (DIEP) flaps. The use of DIRT during the pre-, per- and postoperative period is assessed.

During review of the literature in chapter 3 we noticed that no standardized measurement set-up had been described for the use of DIRT during breast reconstructions with DIEP flaps. In Chapter 4 we describe a new standardized and reproducible measurement set-up for the use of DIRT during breast reconstructions with a free DIEP flap that is applicable during all phases of the reconstruction.

Chapter 5 consists out of 2 parts. In part 1 we investigate the use of our standardized measurement set-up of DIRT for breast reconstructions with DIEP flaps in a preliminary clinical report. In part 2 of this chapter we present the results of the use of DIRT in 33 breast reconstructions by means of a DIEP flaps in 21 patients after mastectomy. This standardized measurement set-up was used for all the flaps in the pre-, intra- and postoperative period.

In the general discussion of this doctoral thesis I will outline the results obtained in the previous chapters. I will discuss future goals of the use of DIRT in breast reconstruction.

19 Aims and outline

References

1. Macadam SA, Bovill ES, Buchel EW, Lennox PA. Evidence-Based Medicine: Autologous Breast Reconstruction. Plast Reconstr Surg. 2017;139:204e-29e. 2. Serletti JM, Fosnot J, Nelson JA, Disa JJ, Bucky LP. Breast reconstruction after breast cancer. Plast Reconstr Surg. 2011;127:124e-35e. 3. Blondeel PN. One hundred free DIEP flap breast reconstructions: a personal experience. Br J Plast Surg. 1999;52:104-11. 4. Healy C, Allen RJ, Sr. The evolution of perforator flap breast reconstruction: twenty years after the first DIEP flap. J Reconstr Microsurg. 2014;30:121-5. 5. Tondu T, Tjalma WAA, Thiessen FEF. Breast reconstruction after mastectomy. Eur J Obstet Gy- necol Reprod Biol. 2018;230:228-32. 6. Rozen WM, Garcia-Tutor E, Alonso-Burgos A, Acosta R, Stillaert F, Zubieta JL, et al. Planning and optimising DIEP flaps with virtual surgery: the Navarra experience. J Plast Reconstr Aesthet Surg. 2010;63:289-97. 7. Mohan AT, Saint-Cyr M. Advances in imaging technologies for planning breast reconstruction. Gland Surg. 2016;5:242-54. 8. Khouri RK. Avoiding free flap failure. Clin Plast Surg. 1992;19:773-81.

20 Chapter 1

Breast reconstruction

Chapter 1 Part A

Breast reconstruction after breast conservation therapy

This chapter has been published as: Filip Thiessen, Wiebren Tjalma and Thierry Tondu. Breast reconstruction after breast conservation therapy for breast cancer. Eur J Obstet Gynecol Reprod Biol. 2018 Nov;230:233-238. doi: 10.1016/j.ejogrb.2018.03.049. Epub 2018 Mar 27. Chapter 1A: Contents

Abstract 25 1.1. Introduction 26 1.2. Oncologic and cosmetic outcome of breast conservative treatment (BCT) 26 1.3. Timing of reconstructive procedures after breast conservative treatment 27 1.3. Reconstructive techniques after breast conservative treatment 28 Immediate 28 Delayed reconstruction 33 1.4. Conclusion 34 1.5. References 35 Breast reconstruction after breast conservation therapy for breast cancer

Abstract

Conservative breast surgery followed by irradiation, often referred to as Breast conserving therapy (BCT), has replaced modified radical mastectomy for the treatment of early stage invasive breast cancer and ductal carcinoma in situ (DCIS). About 10 % to 40% of the patients treated with BCT have poor cosmetic outcome results. Small tumours in large breasts can be successfully treated by lumpectomy and radiotherapy, with good cosmetic outcome. However when the tumour breast ratio is higher, the cosmetic outcome can be very disappointing. A surgical conflict arises between optimal oncologic resection and the desire to spare as much tissue as possible to minimize the risk of deformities. In case of a small defect lipofilling can be performed. This technique transplants fat grafts from a donor site to the defect in the breast. In case of larger defects there is the option of oncoplastic surgery. Oncoplastic techniques combine the optimal oncological resection with an adequate reconstruction for optimal cosmetic outcome. Oncoplastic techniques allow the breast surgeon to perform a tumour resection with adequate margins and the plastic surgeon will reconstruct the defect during the same procedure for optimal cosmetic outcome.

The use of oncoplastic techniques to reconstruct defects of partial mastectomies (BCT) can be immediate, delayed or immediate delayed. Current breast cancer treatment leads to long-term surivival. It is there for important not only to survive but also life. Therefore the quality of life and good cosmetic outcome is mandatory after breast cancer treatment.

Oncoplastic surgery is based on two techniques: volume displacement and volume replacement. The volume displacement techniques use (dermo)glandular flaps of the breast to fill the resection defect. Volume displacement techniques ideally work when the tumour resection can be incorporated in a breast reduction pattern. A similar technique is used on the contralateral breast to match size and shape. The volume replacement techniques use autologous non-breast tissues to compensate the volume loss after tumour resection. Volume replacement techniques are used when a large resection volume is needed in a small breast. Depending on the location and size of the defect many different flaps can be used for partial breast reconstruction.

25 Chapter 1A

1.1. Introduction

he treatment of breast cancer is a continuous evolving field. Maximizing patients’ survival and minimizing treatment’s morbidity are the keystones in breast cancer treatment and breast cancer research [1]. Conservative surgery followed by breast Tirradiation, often referred to as Breast conserving therapy (BCT), has replaced modified radical mastectomy for the treatment of early stage invasive breast cancer [2-4]. Multiple trials proved equivalent disease-free and overall survival outcomes when patients with early stages of breast cancer are treated with partial mastectomy (lumpectomy/quadrantectomy) and radiation therapy or modified radical mastectomy [2-4].

1.2. Oncologic and cosmetic outcome of breast conservative treatment (BCT)

The primary goal in BCT is achieving tumour free margins, despite all the surgical efforts positive margins can be found in 20% to 40% of the tumour excisions, leading to additional radiotherapy or surgical re-interventions (reexcision or mastectomy) [5-8]. Local recurrences rate after BCT is 1,4% per year. The treatment of breast tumour recurrence is in most patients mastectomy [9]. Larger tumour free margins can reduce local recurrence rates, however optimal margins remain controversial and it may lead to unacceptable cosmetic outcome . Satisfactory cosmetic outcome after BCT is mandatory. Cosmetic results depend on the patient’s age, race, the size and symmetry of the breast, location of the tumour, amount of tissue removed and the amount of radiation given. 10 % to 40% of the patients treated with BCT have poor cosmetic results [10]. Small tumours in large breasts can be successfully treated by standard lumpectomy and radiotherapy, with good cosmetic outcome. However when the tumour breast ratio is higher, the cosmetic outcome after standard lumpectomy can be very disappointing [11]. A surgical conflict arises between optimal oncologic resection and the desire to spare as much glandular tissue as possible to minimize the risk of unacceptable local deformity. This dilemma has led to the evolution of procedures that can both reconstruct the resection defect and prevent the need for mastectomy, the so called oncoplastic techniques [12]. These techniques combine oncological resections with plastic surgery techniques in one single procedure. They allow for local wider tumour excisions, with

26 Breast reconstruction after breast conservation therapy for breast cancer

lower risk of margin involvement and oncologic benefits, while avoiding more extensive surgery (mastectomy) with higher complication and morbidity rates [11, 13]. Introduction of more efficient protocols of neo-adjuvant chemotherapy for the treatment of more aggressive tumours may allow more conservative local treatment [14]. The value of oncoplastic surgery especially increases in those cases, allowing local excision of the tumour.

1.3. Timing of reconstructive procedures after breast conservative treatment

The use of oncoplastic techniques to reconstruct defects of partial mastectomies (BCT) can either be immediate, delayed or immediate delayed. In immediate reconstruction of a partial mastectomy, the goal is to perform simultaneously the tumour resection with appropriate margins and reconstruction. It is often referred to as “oncoplastic surgery”. Immediate reconstruction is performed, whenever it is indicated and feasible in order to operate on non-irradiated breast tissue. Oncoplastic surgery has many advantages over delayed breast reconstruction, such as better cosmetic outcome and lower complication rates [15, 16]. In immediate delayed reconstructions, the procedure is performed in 2 stages. During the first stage the tumour is resected. The reconstruction is delayed until the definitive pathology results are known and the resection margins are free. Immediate delayed reconstruction is often performed when the oncological surgeon is uncertain about the resection margins during the partial mastectomy. Re-excision is sometimes performed before the reconstruction. This technique gives the advantage of performing a reconstruction on non-irradiated breast tissue. The final cosmetic outcome is similar to immediate reconstructions [16]. In delayed reconstruction, the reconstructive surgeon waits until the postoperative and post radiotherapy changes in the deformed breast sta- bilize (at least 6 months after last treatment), in order to assess the deformities of the breast and carefully plan the appropriate reconstruction [11, 13].

27 Chapter 1A

1.3. Reconstructive techniques after breast conservative treatment

Immediate For optimal oncologic and aesthetic outcome, treatment of breast cancer should be performed in a multidisciplinary team. Breast conservative therapy is indicated for early-stage breast cancers; however the success of this technique depends on size of the tumour, location of the tumour and the ratio of the resection specimen to the breast volume [2, 3]. Oncoplastic surgery, or immediate reconstructive surgery after BCT, allows the breast surgeon to excise larger breast tumours without compro- mising the aesthetic outcome [12]. The choice of reconstruction depends on the size and location of the breast tumor and the ratio of resection volume to breast volume (Figure 1.1). Oncoplastic surgery is mainly based on two surgical techniques: 1. Volume displacement techniques use (dermo)glandular flaps of the breast to fill the resection defect. Volume displacement techniques ideally work when the tumour resection can be incorporated in a breast reduction or mastopexy pattern (Figure 1.2). The choice of the pedicle used to carry the nipple-areola complex depends on the location of the tumour. A good knowledge of the blood supply of the breast is mandatory in order to design the pedicles. When breast tumours are localised in zones that are not removed during the breast reduction, a combination of breast reduction and creation of glandular flaps can be used to fill the oncologic defect [10, 11]. A similar reduction technique is used on the contralateral breast to match size and shape. It is suggested to keep the contralateral breast 10% smaller, because of the expected shrinking of the irradiated breast. Complications after those technically challenging procedures are similar to classic reduction mammoplasties [17]. 2. Volume replacement techniques use autologous non-breast tissues to compensate the volume loss after tumour resection. Volume replacement techniques are mainly used when a large resection volume is needed in a relatively small breast. Depending on the location and size of the defect many different flaps can be used for partial reconstruction. Small defects on the lateral side of the breast can be reconstructed with local fascio-cutaneous flap from the subaxillary area that are rotated or advanced in the defect [18]. Latissimus dorsi (LD) myocutaneous flap (Figure 1.4) is indicated to re-

28 Breast reconstruction after breast conservation therapy for breast cancer

Table 1.1. Clough classification. Clough Type of Reconstruction Type I No deformity in affected breast Contralateral breast surgery Asymmetry in volume/shape between breasts Type II Deformed breasts Ipsilateral breast surgery Type III Major deformity of painfull fibrosis Total mastectomy and reconstructie

Inferior Pedicle Superior defect Mammoplasty

Superior Pedicle Inferior defect Mammoplasty Small Volume Tumour/Breast Displacement techniques Superolateral pedicle with inferior medial defect component to defect Superomedial BCT lateral defect pedicle with inferior component to defect

Volume Choice of Dorsi Flap Replacement according to TDAP Large Techniques of defect LICAP Tumour/Breast Mastectomy + Defect > 30%

Figure 1.1. Algorithm used in our department.

construct larger lateral breast defects. The flap is raised on the thoracodorsal system and provides bulk to fill the defect and skin the reconstruct the breast skin defects. The LD flap is a very reliable flap with few complications. Donor site morbidity consists of a scar on the back and some musculature function loss. LD Myosubcutaneous flap of LD mini flap is indicated to reconstruct volume defects in the lateral breast when the overlying skin of the breast can be preserved. The technique is similar to the LD myocutaneous flap, except that the overlying skin is not used. This technique avoids a scar on the back. Even endoscopic raising of the flap is described [19, 20]. Nowadays pedicled perforator flaps are commonly used to reconstruct partial mastectomy defects. The use of perforator flaps completely preserves the function of the underlying muscles, reducing donor site morbidity to a minimum. Almost all partial mastectomy defects can be reconstructed with pedicled perforator flaps [21]. The pedicled ThoracoDorsal

29 Chapter 1A

a b

Figure 1.2. A 65 year old patient with invasive ductal carcinoma in the in- ferolaterale pole of the right breast. The tumour was widely exised. Tumour resection lines were included in reduction lines (a) preoperative views. (b) early postoperative views with irradiation dermatitis. (c) final results.

30 Breast reconstruction after breast conservation therapy for breast cancer

Figure 1.3. A 63 year old patient with depression after BCT of the right breast. Reconstrcuction was performed with lipofilling of the right breast (a) preoperativeviews (b) postoperative views.

31 Chapter 1A

Figure 1.4. A 67 year old patient with BCT of the right upper lateral pole. Reconstruction was performed with latissimus dorsi flap (a) preoperative views (b) postoperative views.

32 Breast reconstruction after breast conservation therapy for breast cancer

Artery Perforator flap (TDAP) is the workhorse for partial mastectomy reconstructions and is based on the thoracodorsal system. Harvesting perforator flaps is feasible when the appropriate perforator is chosen and the dissection is performed meticulously. TDAP flap can be converted into a myocutaneous LD flap when the perforators are to small or not pulsating. The lateral intercostal artery perforator flap (LICAP) is a good alternative to the TDAP flap, although the versatility of the TDAP is larger. The use of the LICAP preserves the LD myocutaneous and TDAP flap for potential future use [22]. Partial flap or total flap losses are very rare complications. Fat necrosis has been observed and can be treated if needed. Postoperative irradiation of the flap and breast tissue sometimes gives unpleasing scars, flap contractures and volume loss. This may lead to additional surgical corrections. Partial breast reconstruction sometimes gives a “plugged-in” appearance, which sometimes improves after radiotherapy [23].

Delayed reconstruction The defect of the breast should be carefully assessed at least six months after completion of the irradiation therapy. During the first year after surgery and irradiation edema occurs and can mask some the volume loss of the breast. Six months after surgery and irradiation scar tissue and fibrosis may lead to more severe breast contour deformities. Several classifications have been proposed to classify breast deformities after BCT and suggest reconstructive options. The group of Berrino was the first group to classify defects after BCT [24]. They focused on the importance of analysing the etiology of the deformity. Four types of deformities were described. Type I, breast deformity due to fibrosis and scar contracture, often associated with displacement of nipple areola complex. Type II, breast deformity due to deficiency of tissue (skin and/or parenchyma). Type III, breast deformity due to general breast retraction with normal skin. Type IV deformity results from severe radiotoxicity with parenchymal retraction and distortion and the skin has severe radiation induced changes. The group of Clough (Table 1.1) altered the classification and based it on the response of reconstruction [25]. In type I the affected breast has no deformity, although there is presence of breast asymmetry. These patients are mainly treated with contralateral breast surgery. Type II patients have deformed breasts, requiring partial reconstruction. Type III breast deformity patients have major breast deformities or diffuse painful fibrosis. These patients are treated with total mastectomy and reconstruction. These classifications can help surgeons to evaluate breast deformities that are results of BCT performed under suboptimal conditions.

33 Chapter 1A

Delayed partial breast reconstruction should be considered when post- BCT deformities occur. However careful pre-operative planning is mandatory. Less reconstructive options are available in patients treated with BCT because of reduced breast volume, scarring and altered vascularity. Post- radiation damage to the breast makes corrections even more challenging and less predictable. Multiple studies estimate the complication rate up to 50% and report less pleasing aesthetic results. Reconstruction techniques are similar to those described for the immediate reconstructive techniques. When the deformity after partial mastectomy with radiation is severe, the best option is completion of mastectomy and autologous reconstruction with the deep inferior epigastric artery perforator (DIEAP) flap [26]. Multiple deformities after BCT can be treated with lipofilling or adipose fat grafting (Figure 1.3). Lipofilling is a technique that uses fat grafts, harvested by liposuction from donor sites such as the abdomen, buttocks and thighs and treated in different ways. Lipofilling appears to be an oncological safe technique with low morbidity in women with history of breast cancer [27, 28].

1.4. Conclusion

Treatment of breast cancer should always be performed in a multidisciplinary approach. Early stage breast cancer can safely be treated by Breast conserving therapy. Careful patient selection, surgical planning and technical execution are essential to success of the surgical treatment. If a minimal breast defect is expected minor revisional surgery with or without contralateral remodelling is often adequate to achieve a good cosmetic outcome. Larger tumour resections can safely be performed with the help of oncoplastic surgery. Oncoplastic surgery provides better cosmetic outcome as partial breast reconstruction. An armantarium of multiple techniques, including volume-displacing techniques and volume replacing techniques, are available to achieve good aesthetic outcome. In our centre, immediate oncoplastic surgery is performed in a 2 team approach. This allows the breast surgeon to excise the breast tumour with an adequate margin and the plastic surgeon reconstructs the defect during the same procedure for optimal cosmetic outcome. Immediate reconstruction provides superior aesthetic outcome with fewer complications. Delayed reconstruction after breast conserving therapy is possible, however the surgical options are more limited and the rate of complications is higher.

34 Breast reconstruction after breast conservation therapy for breast cancer

1.5. References

1. Winchester DP, Cox JD. Standards for diagnosis and management of invasive breast carcinoma. American College of Radiology. American College of Surgeons. College of American Patholo- gists. Society of Surgical Oncology. CA Cancer J Clin 1998; 48: 83-107. doi:10.3322/canjc- lin.48.2.83 2. Fisher B, Anderson S, Bryant J et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002; 347: 1233-1241. doi:10.1056/NEJMoa022152 3. Veronesi U, Cascinelli N, Mariani L et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002; 347: 1227-1232. doi:10.1056/NEJMoa020989 4. Huston TL, Simmons RM. Locally recurrent breast cancer after conservation therapy. Am J Surg 2005; 189: 229-235. doi:10.1016/j.amjsurg.2004.07.039 5. Kaufmann M, Morrow M, von Minckwitz G et al. Locoregional treatment of primary breast cancer: consensus recommendations from an International Expert Panel. Cancer 2010; 116: 1184-1191. doi:10.1002/cncr.24874 6. Meric F, Mirza NQ, Vlastos G et al. Positive surgical margins and ipsilateral breast tumor recurrence predict disease-specific survival after breast-conserving therapy. Cancer 2003; 97: 926- 933. doi:10.1002/cncr.11222 7. Park CC, Mitsumori M, Nixon A et al. Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence. J Clin Oncol 2000; 18: 1668-1675. doi:10.1200/jco.2000.18.8.1668 8. Singletary SE. Surgical margins in patients with early-stage breast cancer treated with breast conservation therapy. Am J Surg 2002; 184: 383-393. doi:10.1016/s0002-9610(02)01012-7 9. Schwartz GF, Veronesi U, Clough KB et al. Consensus conference on breast conservation. J Am Coll Surg 2006; 203: 198-207. doi:10.1016/j.jamcollsurg.2006.04.009 10. Audretsch W. Reconstruction of the partial mastectomy defect: classification and method. In: Spear S, Willey S, Robb G et al, Hrsg. Surgery of the breast: principles and art. Philaderlphia, PA: Lippincott Williams & Wilkins; 2006 11. Hamdi M, Wolfli J, Van Landuyt K. Partial mastectomy reconstruction. Clin Plast Surg 2007; 34: 51-62; abstract vi. doi:10.1016/j.cps.2006.11.007 12. Dillon MF, Hill AD, Quinn CM et al. A pathologic assessment of adequate margin status in breast-conserving therapy. Ann Surg Oncol 2006; 13: 333-339. doi:10.1245/aso.2006.03.098 13. Losken A, Hamdi M. Partial breast reconstruction: current perspectives. Plast Reconstr Surg 2009; 124: 722-736. doi:10.1097/PRS.0b013e3181b179d2 14. Cance WG, Carey LA, Calvo BF et al. Long-term outcome of neoadjuvant therapy for locally advanced breast carcinoma: effective clinical downstaging allows breast preservation and pre- dicts outstanding local control and survival. Ann Surg 2002; 236: 295-302; discussion 302-293. doi:10.1097/01.Sla.0000027526.67560.64

35 Chapter 1A

15. Losken A, Dugal CS, Styblo TM et al. A meta-analysis comparing breast conservation therapy alone to the oncoplastic technique. Ann Plast Surg 2014; 72: 145-149. doi:10.1097/ SAP.0b013e3182605598 16. Waljee JF, Hu ES, Newman LA et al. Correlates of patient satisfaction and provider trust after breast-conserving surgery. Cancer 2008; 112: 1679-1687. doi:10.1002/cncr.23351 17. Spear SL, Pelletiere CV, Wolfe AJ et al. Experience with reduction mammaplasty combined with breast conservation therapy in the treatment of breast cancer. Plast Reconstr Surg 2003; 111: 1102-1109. doi:10.1097/01.Prs.0000046491.87997.40 18. Munhoz AM, Montag E, Arruda EG et al. The role of the lateral thoracodorsal fasciocutaneous flap in immediate conservative breast surgery reconstruction. Plast Reconstr Surg 2006; 117: 1699-1710. doi:10.1097/01.prs.0000209943.13682.42 19. Munhoz AM, Montag E, Fels KW et al. Outcome analysis of breast-conservation surgery and immediate latissimus dorsi flap reconstruction in patients with T1 to T2 breast cancer. Plast Reconstr Surg 2005; 116: 741-752. doi:10.1097/01.prs.0000176251.15140.36 20. Losken A, Schaefer TG, Carlson GW et al. Immediate endoscopic latissimus dorsi flap: risk or benefit in reconstructing partial mastectomy defects. Ann Plast Surg 2004; 53: 1-5. doi:10.1097/01.sap.0000106425.18380.28 21. Hamdi M, Van Landuyt K, Monstrey S et al. Pedicled perforator flaps in breast reconstruction: a new concept. Br J Plast Surg 2004; 57: 531-539. doi:10.1016/j.bjps.2004.04.015 22. Hamdi M, Van Landuyt K, de Frene B et al. The versatility of the inter-costal artery perforator (ICAP) flaps. J Plast Reconstr Aesthet Surg 2006; 59: 644-652. doi:10.1016/j.bjps.2006.01.006 23. Hamdi M. Oncoplastic and reconstructive surgery of the breast. Breast 2013; 22 Suppl 2: S100- 105. doi:10.1016/j.breast.2013.07.019 24. Berrino P, Campora E, Santi P. Postquadrantectomy breast deformities: classification and techniques of surgical correction. Plast Reconstr Surg 1987; 79: 567-572 25. Clough KB, Kroll SS, Audretsch W. An approach to the repair of partial mastectomy defects. Plast Reconstr Surg 1999; 104: 409-420. doi:10.1097/00006534-199908000-00014 26. Blondeel PN. One hundred free DIEP flap breast reconstructions: a personal experience. Br J Plast Surg 1999; 52: 104-111. doi:10.1054/bjps.1998.3033 27. Waked K, Colle J, Doornaert M et al. Systematic review: The oncological safety of adipose fat transfer after breast cancer surgery. Breast 2017; 31: 128-136. doi:10.1016/j. breast.2016.11.001 28. De Decker M, De Schrijver L, Thiessen F et al. Breast cancer and fat grafting: efficacy, safety and complications-a systematic review. Eur J Obstet Gynecol Reprod Biol 2016; 207: 100-108. doi:10.1016/j.ejogrb.2016.10.032

36 Chapter 1 Part B

Breast reconstruction after mastectomy

This chapter has been published as: Thierry Tondu, Wiebren Tjalma and Filip Thiessen. Breast reconstruction after mastectomy. Eur J Obstet Gynecol Reprod Biol. 2018 Nov;230:228-232. doi: 10.1016/j.ejogrb.2018.04.016. Epub 2018 Apr 14*

*I included this article of dr T Tondu in my PhD thesis because it gives a general overview of breast reconstructions, I actively contributed to the article as last author and it leads to a better understanding of my PhD as well. As Dr Tondu is first author of this paper, it is part of his PhD research and therefore not mine. Chapter 1B: Contents

Abstract 39 1.5. Introduction 40 1.6. Primary, secondary and tertiary breast reconstruction 40 1.7. Prosthetic, autologous and composite reconstructions 41 Prosthetic reconstruction 41 Autologous reconstruction (pedicled and free flaps) 42 Pedicled flaps 42 Free flaps 43 The transverse rectus abdominis (TRAM) flap 43 The deep inferior epigastric artery perforator (DIEP) flap 43 The superficial inferior epigastric artery (SIEA) flap 44 The SGAP (Superior gluteal artery perforator) flap and the IGAP (Inferior gluteal artery perforator) flap 44 The anterolateral thigh (ALT) flap 45 Transverse myocutaneous gracilis (TMG) flap – transverse upper gracilis (TUG) flap 45 Profunda femoris artery perforator (PFAP) flap 45 Lumbar artery perforator (LAP) flap 46 The deep circumflex iliac artery (DCIA) flap or Rubens flap – the dog ear flap 46 Composite reconstruction 46 1.8. Bilateral prophylactic surgery and primary breast reconstruction 46 1.9. Conclusion 47 1.10. References 48 Breast reconstruction after mastectomy

Abstract

Reconstructive surgery aims to improve quality of life by recreating a natural-looking breast that is warm to touch. To obtain symmetry and body contour alignment, restoration of volume within the skin envelope is mandatory. The chosen reconstruction technique depends on the characteristics of the diseased breast, the shape and volume of the contralateral breast, and the technical skills of the surgical team. Timing, type and different possibilities of breast reconstruction are discussed.

3939 Chapter 1B

1.5. Introduction

urgery has an important role to play in breast cancer treatment. The survival after breast conservative surgery with radiotherapy is equal to mammectomy. A quality indicator project in Belgium revealed that approximately 40% of women with breast cancer Swill undergo a mastectomy [1]. This figure can be explained in part by the use of breast MRI. Breast MRI allows a better staging, thereby increasing the mammectomy rate [2, 3]. A mammectomy is a lifesaving but mutilating procedure. It is important not only to survive but also life [4]. Therefore, the quality of life and good cosmetic outcome is mandatory after breast cancer treatment [4]. Reconstructive surgery aims to improve quality of life by recreating a natural-looking breast that is warm to the touch. To obtain symmetry and body contour alignment, restoration of volume within the skin envelope is mandatory. The chosen reconstruction technique depends on the characteristics of the diseased breast, the shape and volume of the contralateral breast, and the technical skills of the surgical team. Impor- tantly, the patient’s expectations also need to be considered, as the reconstructed breast will never have a normal appearance.

1.6. Primary, secondary and tertiary breast reconstruction

Reconstruction can occur immediately following mastectomy in a one- stage procedure or be delayed. Primary breast reconstruction is an option when it is oncologically safe and when adjuvant therapy has no influence on the final result. This has a psychological advantage for the patient, who will thus never have the experience of breast amputation. Nevertheless, unrealistic expectations about the final shape and appearance may arise. Secondary breast reconstruction can be performed years after mastectomy. Due to the loss of a skin envelope, a staged procedure is often indicated. In contrast with primary reconstruction, post-operative quality of life improves dramatically when a second breast is reconstructed. Tertiary procedures are salvage procedures that try to solve the complications of the initial breast reconstruction (e.g. prosthetic breast distortion of flap necrosis).

40 Breast reconstruction after mastectomy

1.7. Prosthetic, autologous and composite reconstructions

The advantages and disadvantages of the different types of breast reconstructions are shown in Table 1.2.

Prosthetic reconstruction Prosthetic breast reconstruction remains the most performed method worldwide [5]. Operating time is shorter and concerns with donor site scars, or morbidity, and flap perfusion can be avoided. Implants can be round or anatomical; they can be filled with saline or a cohesive silicone gel, have a textured or micro-textured surface, or be covered in poly-urethane. A lack of breast skin makes a staged approach involving skin expansion necessary. In order to produce symmetry with the contralateral breast, modern implants are available in varying heights, projections and base widths. Very satisfying results are obtained when used in non-ptotic breasts. In ptotic breasts, however, a contralateral corrective procedure is necessary. Rela- tively larger implants can be used, if placed above the pectoral muscle and result in more ptotic breasts. The disadvantages of this technique are a higher risk of rippling in the upper breast pole and the need for sufficient

Table 1.2. Advantages and disadvantages of different types of breast reconstruction. Reconstruction type/ Prosthetic Autologous free flap Autologous pedicled pro-con’s flap Primary reconstruction Yes Yes Yes Secondary reconstruction 2 or more stages 1 stage possible 1 stage possible Procedure Length 1-2h 6h 2-3h Breast behaviour Static Dynamic Dynamic Capsular contraction risk Yes No No (yes when composite) Pre-reconstruction Higher Low (at least 6 months Low radiotherapy complication risk after RTH) Hospital stay Day case 4-5 days 2-3 days Permanent result No Yes Yes Temperature Less warm Body temperature Body temperature Donor site scars No Yes Yes Donor site morbidity No Yes Yes Flap perfusion No Yes Yes Symmetry Small non-ptotic Moderate ptosis and Small non-ptotic breasts volume breasts Ptosis solution No Yes No Rippling Yes No No Emptiness upper breast pole No Sometimes Sometimes

41 Chapter 1B

skin to cover a larger prosthesis. A sub-pectoral prosthesis often lacks a natural ptotic lower breast pole (Figure 1.5). Radiotherapy results in a higher risk of postoperative infection and late capsular contracture [6].

Ptosis grade 0/1 Ptosis grade 2/3

Small to moderate Small to moderate Large breast breast (cup A/B/C) breast (cup A/B/C) (cup D or more)

Staged pedicled Type IV Anatomical MP Anatomical HP NNSM + breast with subcutaneous prosthesis (NSM)/ prosthesis + Expander/ expander and NNSM +:- ADM or expander (NNSM) ADM (NSM) prosthesis secondary dermal pedicle prosthesis (NSM)

Anatomical HP prosthesis + ADM (NSM

Figure 1.5. Primary prosthetic reconstruction. NSM: nipple sparing reconstruction; NNSM: non nipple-sparing reconstruction; MP: moderate profile; HP: high profile; ADM: acellular dermal matrix; type IV subcutaneous mastectomy: Weiss pattern incision subcutaneous mastectomy.

Autologous reconstruction (pedicled and free flaps)

Pedicled flaps The musculocutaneous latissimus dorsi (LD) flap and thoracodorsal artery perforator (TDAP) flap Once the workhorse of breast reconstruction, the LD-flap is nowadays no longer the first choice. Instead, the Deep Inferior Epigastric artery Per- forator (DIEP), which is harvested without muscle damage and provides a greater quantity of vascularized tissue, has taken it place. Furthermore, a reliable vascular supply can be derived from the descending and transverse branches of the thoracodorsal artery. The TDAP flap is a muscle-sparing flap usually harvested on a perforating vessel overlying the descending branch of the thoracodorsal artery [7]. The large skin paddle can be positioned transversely of more obliquely, such that the donor scar lies along a natural crease. Subcutaneous bevel- ling will provide more fatty tissue and the medial breast mound can be adequately reached. The transveres diameter of the flap is as large as the base of the amputated breast. As tissue expander or prosthesis can add extra volume to the breast.

42 Breast reconstruction after mastectomy

Another possibility for augmenting volume is fat grafting, immediately before harvesting the flap or as a secondary procedure [8]. If a prosthesis is used, greater latissimus dorsi muscle volume can be included in the flap to provide complete muscle coverage of the prosthesis of expander. Prepared with only one perforator, the muscle-sparing thoracodorsal artery perforator flap is used in the same manner as the LD-flap [9].

Free flaps The idea of “like by like” replacement refers to reconstruction of a natural-looking, warm and ptotic breast that resembles the contralateral side. Evolution in microsurgery now allows transplantation and replacement of large volumes of autologous tissue, even from anatomically remote areas

The transverse rectus abdominis (TRAM) flap As microsurgical skills and experience have advanced, the rates of flap loss in high volume centres have diminished. The TRAM flap uses the deep inferior epigastric artery and vein to supply and drain the transplanted musculocutaneous tissue. Additional preparation and anastomosis of the superficial inferior epigastric vein improves venous drainage, thus improving safety with the technique. Although the results of reconstruction are satisfactory, considerable donor site morbidity can occur. Rectus muscle damage with consequent abdominal wall herniation and bulging is frequently reported [10].

The deep inferior epigastric artery perforator (DIEP) flap The main goal of the perforator flap is to diminish donor site morbidity by sparing the muscles and improving function and strength. Although the DIEAP flap has become the golden standard in microsurgical breast reconstruction, a recent review was unable to demonstrate any superiority compared with pedicled abdominal flaps [11]. Nevertheless, sparing of abdominal wall strength is preferred to muscle weakness. Due to its vascular supply and microvascular branching, sufficient tissue can be provided in most patients. A bilateral blood supply allows for simultaneous bilateral reconstruction and conservation of abdominal wall integrity diminishes the complications rate significantly [10]. The length of the skin paddle and volume of the flap allows creation of a ptotic breast, which avoids contralateral surgery. Recently, lymph node transplants have been included in the flap. Specific shaping of the breast with positioning of nodes in the axilla, creates lymphatic drainage in a lymph-oedema-affected arm [12]. (Figure 1.6)

43 Chapter 1B

Figure 1.6. Preoperative and postoperative view after 1 year of a subcutaneous mastectomy left and primary DIEAP flap reconstruction left, left nipple and areola reconstruction, bilateral tattouage of nipple and areola- complex and a contralateral breast reduction with inferior pedicle.

Preoperative evaluation of the flap microvasculature by ultrasound or by computed tomografphic angiography allows evaluation of the pedicle anatomy as well as the perforators and their distribution within the flap [13]. Per-operative indocyanine mapping is an important tool for identifying poorly vascularized distal flap areas, thus helping to prevent fat necrosis or partial flap necrosis [14].

The superficial inferior epigastric artery (SIEA) flap The SIEA flap can be an alternative to the DIEAP flap, although these vessels dominate in only 30% of patients [15]. A shorter pedicle is obtained due to distal positioning of the vessels. The principle advantage is the absence of any abdominal wall morbidity, but flap shaping is less versatile and distal necrosis occurs more easily due to the more superficial vascular supply.

The SGAP (Superior gluteal artery perforator) flap and the IGAP (Inferior gluteal artery perforator) flap The SGAP and IGAP flaps are baded on cutaneous perforators of the superior and inferior gluteal arteries respectively. These are terminal branches of the internal iliac artery. If the abdominal wall cannot be used, these

44 Breast reconstruction after mastectomy

flaps provide a satisfactory alternative. In a series of 170 GAP flaps, Guerra described a 6% rate of vascular complications requiring anastomotic revi- sion. Total flap failure rate was 2% [16]. This technique is ideally suited to reconstruction of small to moderately sized breasts. Donor site scar visibility and morbidity are minimal. Dissection can be tedious, however and may give rise to limited pedicle length. The procedure also requires a change in body positioning during surgery.

The anterolateral thigh (ALT) flap The anterolateral thigh (ALT) flap is based on septocutaneous or musculocutaneous perforators of the descending branch of the lateral circumflex artery, a branch of the deep femoral artery. Extensively used in head and neck reconstruction, its pliability and large skin paddle makes it an alternative for breast reconstruction in moderately sized breast, although the position of the scar may not be acceptable to some patients. The pedicle length is up to 10 cm and Wei described a total failure rate of 1.79% [17].

Transverse myocutaneous gracilis (TMG) flap – transverse upper gracilis (TUG) flap The TMG or TUG flap is perfused by the ascending branch of the medial circumflex femoral artery supplying the gracilis muscle. The pedicle is short (6 cm) and the flap size is limited by the volume of tissue available on the inner thigh. The skin paddle is transverse or combined with a vertical part (fleur-de-lis). Coning of the flap results in an acceptable projecting breast shape. The thigh adductor muscles compensate for functional morbidity with loss of the gracilis muscle. Anterior dissection with disruption of lymphatic vessels in the femoral triangle must be avoided. Donor site dehiscence may prolong healing and as is observed in inner thigh lift procedures, the scar may sag beneath the bikini-line. These flaps are an alternative for small to moderate breast reconstructions in women who want to avoid scars on the abdomen, the back or the buttocks, or for patients who have previously undergone abdominoplasty or liposuction. Slim patients who lack sufficient abdominal tissue or who are unable to have an implant reconstruction are also appropriate candidates [18].

Profunda femoris artery perforator (PFAP) flap The PFAP flap has a long pedicle (10-13 cm) and is prepared using the proximal musculocutaneous perforator of the first medial branch of the profunda femoris artery. Excess tissue on the posteromedial inner thigh is used. The skin paddle is elliptical with a maximal width of 10 cm allow-

45 Chapter 1B

ing primary closure. This technique is used for small to moderately sized breasts. As in the TUG flap, there is an elevated risk of wound dehiscence. The donor site is well hidden in the crease although sagging occurs [19].

Lumbar artery perforator (LAP) flap The LAP flap contains excess skin and fat tissue extending from the lower back to upper buttock. In a series of 35 LAP flaps by Peters, a vessel inter- position graft was necessary in 80% to correct pedicle length or recipient vessel mismatch. Larger flaps can be harvested by gluteal extension [20].

The deep circumflex iliac artery (DCIA) flap or Rubens flap – the dog ear flap The DCIA flap uses fatty tissue in the region overlying or just above the iliac crest. It is a second choice after previous abdominoplasty, as a salvage procedure after failed free flap breast reconstruction or as a second free flap in case of contralateral breast cancer. Donor site morbidity is minimal when the abdominal wall musculature is closed correctly. Recently, Cole- bunders has use the lateral dog ears remaining after DIEAP breast reconstruction donor site closure, as a DCIA perforator flap [21].

Composite reconstruction Combining autologous tissue with foreign material has been used for decades (e.g. LD-flap with a prosthesis). Skin flap thickness for prosthesis coverage is a problem in a pre-pectoral position or in the lower lateral quadrant in a sub-pectoral position. An acellular dermal matrix is an additional tool for resolving these problems [22]. Recently, fat graftin has been used to improve upper pole prosthesis coverage in a staged procedure (se- rial deflation-lipofilling), allowing use of a much smaller prosthesis [23].

1.8. Bilateral prophylactic surgery and primary breast reconstruction

5%-7% of breast cancer cases are due to a genetic defect. Women with mutations have an elevated lifetime risk of developing breast cancer. Imme- diate prosthesis reconstruction after bilateral preventive skin and/or nipple sparing mastectomy is challenging due to poor dermal vascularization of the mastectomy flaps. Changing nipple position results in a higher risk of nipple necrosis [24]. Figure 1.7 shows a successfully staged technique with bilateral nipple and areola sparing mastectomy. Immediate prosthetic reconstruction should only be considered in small, non-ptotic breasts.

46 Breast reconstruction after mastectomy

Figure 1.7. Preoperative and postoperative view after 1,5 year of a staged prophyllactic procedure with bilateral reduction mammaplasty followed by bilateral nipple and areola sparing mastectomy, skin expansion and definite bilateral subpectoral prosthesis reconstruction

Bilateral DIEAP flaps are the autologous golden standard. Secondary correction of ptosis or removal of the monitoring free flap skin island is usually necessary.

1.9. Conclusion

Over the last three decades, a multidisciplinary surgical approach has resulted in an exponential growth in breast reconstruction possibilities. A breast that appears and feels realistic should be created using low-risk surgery, especially in genetically predisposed young women. Perforator flap surgery is nowadays the ultimate tool for reducing functional donor site morbidity. Evolution in prosthesis types and materials such as acellular matrices is largely responsible for the increased number of prosthetic reconstructions worldwide. The trained plastic microsurgeon has a vast armamentarium for dealing with challenging tertiary procedures in case of flap loss or late major prosthetic complications such as severe recurrent capsular fibrosis. Secondary morbidities such as lymph-oedema can simultaneously be addressed in specific autologous procedures. Finally, artistically performed composite surgeries can sculpt a definite breast shape. 3D bio-printing by tissue engineering and stem cell technology are promising techniques for the future.

47 Chapter 1B

1.10. References

1. https://www.zorgkwaliteit.be/ziekenhuis.universitair-ziekenhuis-antwerpen/borstkanker. assessed March 31, 2018 2. Van Goethem M, Schelfout K, Kersschot E et al. Enhancing area surrounding breast carcinoma on MR mammography: comparison with pathological examination. Eur Radiol 2004; 14: 1363- 1370. doi:10.1007/s00330-004-2295-3 3. Van Goethem M, Schelfout K, Kersschot E et al. MR mammography is useful in the preoperative locoregional staging of breast carcinomas with extensive intraductal component. Eur J Radiol 2007; 62: 273-282. doi:10.1016/j.ejrad.2006.12.004 4. Thiessen FEF, Tjalma WAA, Tondu T. Breast reconstruction after breast conservation therapy for breast cancer. Eur J Obstet Gynecol Reprod Biol 2018; 230: 233-238. doi:10.1016/j. ejogrb.2018.03.049 5. Panchal H, Matros E. Current Trends in Postmastectomy Breast Reconstruction. Plast Reconstr Surg 2017; 140: 7s-13s. doi:10.1097/prs.0000000000003941 6. Fernandez-Frias AM, Aguilar J, Sanchez JA et al. Immediate reconstruction after mastectomy for breast cancer: which factors affect its course and final outcome? J Am Coll Surg 2009; 208: 126- 133. doi:10.1016/j.jamcollsurg.2008.09.005 7. Saint-Cyr M, Nagarkar P, Schaverien M et al. The pedicled descending branch muscle- sparing latissimus dorsi flap for breast reconstruction. Plast Reconstr Surg 2009; 123: 13-24. doi:10.1097/PRS.0b013e3181934838 8. Zhu L, Mohan AT, Vijayasekaran A et al. Maximizing the Volume of Latissimus Dorsi Flap in Au- tologous Breast Reconstruction with Simultaneous Multisite Fat Grafting. Aesthet Surg J 2016; 36: 169-178. doi:10.1093/asj/sjv173 9. Hashem T, Farahat A. Thoracodorsal artery perforator flap as an autologous alternative to acellular dermal matrix. World J Surg Oncol 2017; 15: 185. doi:10.1186/s12957-017-1254-9 10. Knox AD, Ho AL, Leung L et al. Comparison of Outcomes following Autologous Breast Recon- struction Using the DIEP and Pedicled TRAM Flaps: A 12-Year Clinical Retrospective Study and Literature Review. Plast Reconstr Surg 2016; 138: 16-28. doi:10.1097/prs.0000000000001747 11. Lee BT, Agarwal JP, Ascherman JA et al. Evidence-Based Clinical Practice Guideline: Autologous Breast Reconstruction with DIEP or Pedicled TRAM Abdominal Flaps. Plast Reconstr Surg 2017; 140: 651e-664e. doi:10.1097/prs.0000000000003768 12. Saaristo AM, Niemi TS, Viitanen TP et al. Microvascular breast reconstruction and lymph node transfer for postmastectomy lymphedema patients. Ann Surg 2012; 255: 468-473. doi:10.1097/ SLA.0b013e3182426757 13. Schrogendorfer KF, Nickl S, Keck M et al. Viability of five different pre- and intraoperative imaging methods for autologous breast reconstruction. Eur Surg 2016; 48: 326-333. doi:10.1007/ s10353-016-0449-6 14. Burnier P, Niddam J, Bosc R et al. Indocyanine green applications in plastic surgery: A review of the literature. J Plast Reconstr Aesthet Surg 2017; 70: 814-827. doi:10.1016/j.bjps.2017.01.020

48 Breast reconstruction after mastectomy

15. Henry FP, Butler DP, Wood SH et al. Predicting and planning for SIEA flap utilisation in breast reconstruction: An algorithm combining pre-operative computed tomography analysis and intra-operative angiosome assessment. J Plast Reconstr Aesthet Surg 2017; 70: 795-800. doi:10.1016/j.bjps.2017.03.011 16. Guerra AB, Metzinger SE, Bidros RS et al. Breast reconstruction with gluteal artery perforator (GAP) flaps: a critical analysis of 142 cases. Ann Plast Surg 2004; 52: 118-125. doi:10.1097/01. sap.0000095437.43805.d1 17. Wei FC, Jain V, Celik N et al. Have we found an ideal soft-tissue flap? An experience with 672 anterolateral thigh flaps. Plast Reconstr Surg 2002; 109: 2219-2226; discussion 2227-2230. doi:10.1097/00006534-200206000-00007 18. Patel NG, Ramakrishnan V. Microsurgical Tissue Transfer in Breast Reconstruction. Clin Plast Surg 2017; 44: 345-359. doi:10.1016/j.cps.2016.12.002 19. Allen RJ, Haddock NT, Ahn CY et al. Breast reconstruction with the profunda artery perforator flap. Plast Reconstr Surg 2012; 129: 16e-23e. doi:10.1097/PRS.0b013e3182363d9f 20. Peters KT, Blondeel PN, Lobo F et al. Early experience with the free lumbar artery perforator flap for breast reconstruction. J Plast Reconstr Aesthet Surg 2015; 68: 1112-1119. doi:10.1016/j.bjps.2015.03.031 21. Colebunders B, Depypere B, Van Landuyt K. The dog-ear flap as an alternative for breast reconstruction in patients who have already undergone a DIEAP flap. J Plast Reconstr Aesthet Surg 2016; 69: 594-597. doi:10.1016/j.bjps.2015.10.005 22. Nahabedian MY. Acellular dermal matrices in primary breast reconstruction: principles, concepts, and indications. Plast Reconstr Surg 2012; 130: 44s-53s. doi:10.1097/ PRS.0b013e31825f2215 23. Sommeling CE, Van Landuyt K, Depypere H et al. Composite breast reconstruction: Implant- based breast reconstruction with adjunctive lipofilling. J Plast Reconstr Aesthet Surg 2017; 70: 1051-1058. doi:10.1016/j.bjps.2017.05.019 24. Tondu T, Thiessen F, Tjalma WA. Prophylactic Bilateral Nipple-sparing Mastectomy and a Staged Breast Reconstruction Technique: Preliminary Results. Breast Cancer (Auckl) 2016; 10: 185-189. doi:10.4137/bcbcr.S40033

Chapter 2

The evolution of breast reconstructions with free flaps: a historical overview

This chapter has been submitted to Clinical Breast Cancer as: Filip Thiessen, Nicolas Vermeersch, Thierry Tondu, Veronique Verhoeven, Lawek Bersenji, Guy Hubens, Gunther Steenackers , Wiebren Tjalma. The evolution of breast reconstructions with free flaps: a historical overview. Chapter 2: Contents

Abstract 53 2.1. Introduction 54 2.2. A new era 55 2.3. Abdominal flaps 55 2.4. Detection of perforator location 58 2.5. Gluteal flaps 60 2.6. Thigh flaps 61 Medial thigh 61 Posterior thigh 62 Lateral thigh 62 Lower back 62 2.7. Future of breast reconstructions 63 2.8. Conclusion 63 2.9. References 65 The evolution of breast reconstructions with free flaps

Abstract

Breast cancer is the most frequent cancer among women and is responsible for the highest number of cancer-related deaths. Approximately 40 percent of the patients with breast cancer will undergo a mastectomy. Breast amputation is a lifesaving but mutilating procedure. Therefore a good quality of life and a good cosmetic outcome is mandatory after breast cancer treatment. Reconstructive breast surgery aims to recreate a natural looking breast that is warm, soft and feels natural. The chosen reconstruction technique depends on the physiognomy of the patient, technical skills of the surgeon and most important the expectations of the patient. The idea of “like-by-like” replacement refers to reconstruction of a natural-looking, warm, soft and ptotic breast that matches the contralateral side. Autologous breast-reconstruction matches these expectations.

Autologous breast reconstructions with free flaps evolved from prolonged and laborious procedures with only limited free flaps available, to routine surgeries with a widespread availability of flaps to use. The first publication of free tissue transfer for breast reconstruction was in 1976 by Fujino. Two years later Holmström was the first to use the abdominal pannus for breast reconstruction. Over the next 4 decades multiple free flaps have been described. The possible options for donor site are the abdomen, the gluteal region, the thigh and the lower back. During this evolution the reduction of donor site morbidity became more important.

Present article gives an overview of the evolution of free tissue transfer in breast reconstruction, highlighting the most important milestones.

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2.1. Introduction

reast cancer is the most common cancer in women worldwide[1]. In 2018 there were over 2 milion cases. Belgium is the country with the highest rate of breast cancer in the world (113/100.000). The 5 years survival in Belgium is 83 %, which is Bequal to the average five year survival for breast cancer in Europe (82%) [2]. The keystones in breast cancer treatment are patient’s survival and minimizing treatment’s morbidity. Approximately 40 percent of the patients with breast cancer undergoes a mastectomy. Breast amputation is a lifesaving but mutilating procedure. Therefore a good quality of life and a good cosmetic outcome is mandatory after cancer surgery [3]. Reconstruc- tive breast surgery aims to recreate a natural looking breast that is warm to touch [4]. The chosen technique, either implant-based or autologous breast reconstruction, depends on the physiognomy of the patient, technical skills of the surgical team and most important the expectations of the patient. The idea of “like-by-like” replacement refers to reconstruction of a natural-looking, warm, soft and ptotic breast that matches the contralateral side. Autologous breast reconstruction matches these expectations. Verneuil was the first to describe the use of autologous tissue to reconstruct the breast in 1887, with breast tissue from one side transferred on a pedicle to reconstruct the opposite side [5, 6]. Vincent Czerny, a Ger- man surgeon, was credited with the first successful autologous breast reconstruction after mastectomy. He described an autotransplantation of a lipoma from the patient’s lumbar region to the mastectomy side [6, 7]. This success generated a search for multiple autologous methods to reconstruct the breast. Pedicled locoregional flaps such as the musculocutaneous latissimus dorsi (LD)-flap and the transverse rectus abdominis myocutaneous (TRAM)-flap were the workhorse flaps for years [8]. Evolution in microsurgery now allows transplantation of large volumes of autologous tissue from an anatomically remote area [9]. Over the last four decades a tremendous evolution has been seen in this part of reconstructive surgery. Autologous breast reconstructions with free flaps evolved from prolonged and laborious procedures with only limited flaps available, to routine surgeries with a widespread availability of potential flaps to use. While implant-based breast reconstruction is an important and frequently used technique, this article aims to present an overview of the evolution of free tissue transfer in breast reconstruction, highlighting the most important milestones.

54 The evolution of breast reconstructions with free flaps

2.2. A new era

In 1976 Fujino published the first case report of a free tissue transfer to reconstruct a breast after radical mastectomy. A skin-fat-muscle flap from the upper portion of the greater gluteal muscle was harvested including the superior gluteal artery and vein. A successful microvascular anastomosis was performed connecting the superior gluteal vessels to the thora- coacromial artery and lateral thoracic vein. The same authors reported the use of a gluteal free flap for the reconstruction of a congenital aplastic breast [10, 11]. In 1978, Serafin et al. were the first to describe a series of free flaps to reconstruct the breast after radical mastectomy. Ten groin flaps and two contralateral LD-flaps were used in combination with an implant in twelve patients [12]. Holmström was the first to use the abdominal pannus as donor site to reconstruct the breast. This flap was called the free abdominoplasty flap, which was based on the inferior epigastric vessels and a superficial vein [13]. Basically Holmstöm was the first to describe and perform a free TRAM flap.

2.3. Abdominal flaps

Holmström’s work drew attention to the availability of the abdominal donor site for microsurgical breast reconstruction. However, the idea to use the excess of abdominal fat was not new. In 1943 Sir H. Gillies already performed breast reconstructions by tubing the excess of abdominal fat to the trunk over several stages [14]. In 1979, the first pedicled rectus abdominis myocutaneous flap was reported by Robbins with a vertically designed skin island. This design resulted in inappropriate scarring on the abdomen [15]. The use of the abdominal tissue for breast reconstruction was not popularized until 1982, when Hartrampf published his work on the pedicled “transverse abdominal island flap”. Clinical observations during abdominoplasty procedures revealed that the abdominal pannus remains vascularized and can be islanded when it is only attached to the anterior rectus sheath. This clinical research revealed that a musculocutaneous flap can be elevated on the deep superior epigastric vessels. Three designs of this musculocutaneous flap were described; the vertical-, the horizontal upper- and the horizontal lower rectus abdominis musculocutaneous flap. The latter is known as the pedicled TRAM flap. Reported advantages were well vascularized tissue, large arc of rotation and usage of abdominal fat obviating the use of an additional implant, resulting in a durable and natu-

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ral appearing breast [16]. Despite the excellent results with pedicled TRAM flaps, important shortcomings were encountered. The risk of abdominal hernia was already described in the first report by Hartrampf. Vascular complications on the other hand were reported by Scheflan and Dinner in their own described zones III and IV, which we peculiarly know as the Har- trampf perfusion zones of the abdominal flap. Strict patient selection was essential to avoid vascular complications [17]. The potential vascular complications are accountable to the dominance of the deep inferior epigastric artery in supplying the skin of the anterior abdominal wall, as proven by Boyd in 1984 [18]. A free abdominal flap, requiring microvascular transfer, based on the inferior epigastric pedicle was growing popular in the mid to late 1980s to overcome the vascular problems. Friedman was the second, after Holmström in 1979, to report a case of a free TRAM flap in 1985 with excellent results [19]. The teams of Arnez and Grotting improved the operative technique and surgical outcome. The free TRAM flap has a superior perfusion compared to the pedicled TRAM flap by using the dominant vascular supply. On top of a better vascularization the free TRAM flap gives an improved medial contour, maintains the inframammary fold due to the lack of tunneling the rectus muscle and lastly a TRAM flap needs a more limited rectus muscle harvest. The length and size of the pedicle allows for feasible microvascular anastomosis. Recipient vessels were branches of the axillary vessels in all cases. The free TRAM flap was favorable concerning complications, operating time, estimated blood loss, hospitalization, and return to functional baseline [20, 21]. The introduction of perforator flaps, composed exclusively of skin and subcutaneous tissue, represented a significant advance in microsurgical reconstructions. The first publication in 1988 on this new type of flap described the reconstruction of low posterior midline defects with perforator flaps [22]. Koshima and Soeda were the first to describe a perforator flap of the anterior abdominal tissue in 1989. They described an inferior epigastric artery skin flap without rectus abdominis muscle to reconstruct a groin defect as a pedicled island flap and to reconstruct the oral floor as a free flap. This large flap without muscle could survive on a single muscle perforator [23]. Advantages of perforator flaps are reduced donor-site morbidity, longer pedicles compared to musculocutaneous flaps and more freedom in orientation of the pedicle [24]. Allen and Treece developed in 1994 the deep inferior epigastric artery perforator flap (DIEP) for breast reconstruction after mastectomy. The technique has all of the advantages of the free TRAM flap with decreased risk for abdominal weakness, bulging or hernia due to complete muscle preservation [25]. Blondeel published in the same

56 The evolution of breast reconstructions with free flaps

year his refinements to the technique. He performed the first bipedicled DIEP flap for single breast reconstruction, using the internal mammary artery as recipient vessel [26]. In 1997 Blondeel confirmed the superiority of DIEP flaps compared to free TRAM flaps in donor site morbidity. The long term benefits for the patient outweigh the increased surgical complexity, operating times and cost involved in DIEP flap breast reconstruction [27]. In 1991, Grotting was the first to perform a breast reconstruction with abdominal tissue based on the superficial epigastric artery and vein with complete sparing of the rectus abdominis muscle and fascia [28]. More experience with this flap was presented by Arnez in 1999. The advantages of this flap are the fast and easy dissection and absence of any potential muscular disturbance. However there are some major drawbacks related to this technique: size and length of the pedicle is considerably less compared to DIEP flap, unfavorable pedicle orientation arising from the flap border, unreliable perfusion across the midline and inconsistent anatomy of this vessels [29]. In 1994 a breast reconstruction with a free musculocutaneous flap based on the the deep circumflex iliac artery of the lateral abdomen was described by Hartrampf [30]. The so called Rubens flap can be used when the abdominal pannus is not available [31]. Later it was refined as a perforator flap and it’s first use in breast reconstruction was described by Buchel [32]. Over the years, the DIEP flap has become the gold standard for autologous breast reconstruction and different pioneers of the DIEP flap have published their experience with this technique [33-36]. In 2002, Nahabedi- an added the concept of a muscle sparing (MS)TRAM-flap, depending on the amount of rectus muscle that is preserved [36] (Table 2.1).

Table 2.1. History of the abdominal pannus as donor site in breast reconstruction: 1979 Report of the first abdominal free flap for breast reconstruction “free abdominoplasty flap”, later known as the free TRAM flap - Holmström et al. [13] 1979 Description of the first pedicled rectus abdominis myocutaneous flap with vertical designed skin island - Robbins et al. [15] 1982 Description of the pedicled TRAM flap - Hartrampf et al. [16] 1991 First abdominal free flap based on the superficial epigastric vessels for breast reconstruction, later known as the SIEA flap – Grotting et al.[28] 1994 Description of the DIEP flap in breast reconstruction – Allen et al. [25] 1994 First bilateral DIEP flap breast reconstruction – Blondeel et al. [26] Abbreviations: TRAM = transverse rectus abdominis myocutaneous, SIEA = superficial inferior epigastric artery, DIEP = deep inferior epigastric perforator

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In general, the abdominal donor site was already established in breast reconstruction for its volume, color and texture resemblance with native breast tissue and for its potency to match a ptotic opposite breast that tends to age in a natural fashion. Therefore attention shifted to decreasing donor site morbidity. This was seen over the years by altering techniques from pedicled to free TRAM flap, to free MS-TRAM flap, DIEP flap and SIEA flap. Progress comes at a price however.

2.4. Detection of perforator location

Due to the increased complexity of perforator flaps such as the DIEP flap, a higher risk for (partial) flap failure, venous congestion and fat necrosis is observed [37, 38]. Selection of the best perforator vessels is the key in perforator flap surgery. This will reduce operative time, lower complication rates and ensure an overall better result [39]. Current techniques to locate the perforator vessels include handheld Doppler, color Doppler ultrasound (CDU), Magnetic Resonance Angiography (MRA), computer tomographic angiography (CTA) and dynamic infrared thermography (DIRT) [40-43]. Ta- ble 2.2 compares the different techniques. The current gold standard to map the perforators is CTA on which the location and hemodynamic properties of the flap can be assessed [40-42]. CTA replaced CDU over the years. CDU is a safe and cheap technique that gives information on the diameter and blood flow characteristics of the perforator vessels, but is has a high inter-observer variability and a high number of false positives compared to CTA [40, 41, 44-47]. Moreover it is a time consuming examination. CTA is frequently used because it is non-invasive and has a high spatial resolution with visualization of the intramuscular course of the vessels. However, this technique has disadvantages, such as the use of intravenous (IV) contrast agents and ionizing radiation, high purchasing costs, a lack of perioperative usability, and a lack of physiological information on flow characteristics [40]. DIRT has gained in popularity as an alternative technique in perforator mapping [42]. DIRT is less invasive than CTA because it does not use radiation nor contrast agents. It is based on measurements of heat emission by tissues and skin temperature with the use of infrared (IR)-cameras. Data obtained with DIRT are used to generate color-coded maps that correlate with the perfusion of the skin. DIRT is generally used as a dynamic investigation technique, meaning that the skin must undergo a thermal cold challenge. After this cold challenge, DIRT measures the rate and patterns of rewarming. With this method, clinicians are able to identify the most

58 The evolution of breast reconstructions with free flaps

dominant perforators and their perfusion area [43, 48]. Earlier studies have shown that DIRT is a valuable addition during breast reconstructions with DIEP flaps pre, per-, and post-operatively [45, 46, 48-53]. DIRT is a valuable alternative to clinical examination to evaluate at any stage during surgery the perfusion of the flap [42]. DIRT can also be an interesting alternative to the use of indocyanine green (ICG) to evaluate the microcirculation and perfusion of the flap peroperatively. DIRT is less invasive than the use of ICG because there is no need for contrast agents. Moreover the potential allergic reactions to ICG should be taken into consideration [54]. Further- more, DIRT is easy to interpret and has a low purchasing cost. DIRT only provides information on the physiology of the perforator and not on the morphology [43]. Nevertheless, adding DIRT during breast reconstructions with DIEP flaps is a helpful tool [42, 43, 46]. This opens also possibilities for its use in other free flaps. The abdominal donor site is not always available, for example in cases of insufficient soft-tissue bulk, history of abdominoplasty, or multiple abdominal scars. With increasing numbers of patients requesting autologous reconstructions other donor sites are considered [55].

Table 2.2. Comparison of various tools for assessing characteristics of the perforators. CDU CTA DIRT Cost Cheap Expensive Cheap Radiation and contrast No Yes No Easy to perform and interpret by surgeon No No Yes Operator dependent Yes No No Time consuming Yes Yes No Applicable in all phases of DIEP (pre-, per- and postoperative) No No Yes Information on flow (physiology) Yes No Yes Information on perfusion No No Yes 3D images No Yes No Precise anatomical description (morphology) No Yes No CDU: Color Doppler ultrasound CTA: Computed Tomography Angiography DIRT: Dynamic Infrared Thermography

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2.5. Gluteal flaps

After the initial report of Fujino 1976, using a superior gluteal myocutaneous free flap, Le-Quang performed the first breast reconstruction with an inferior gluteal myocutaneous free flap in 1978 [11, 56]. Shaw popularized breast reconstructions by means of the superior gluteal myocutaneous free flap, with excellent results and minor donor site morbidity. However, due to inherent short vascular pedicle, a venous graft was often necessary, consequently constraining its use [57]. The inferior gluteal myocutaneous free flap was further elaborated by Paletta in 1989. Despite increased length of the vascular pedicle and a more discrete scar compared to the superior gluteal flap, the inferior gluteal flap never grew as popular because of the close relation to the sciatic nerve with potential injury and more pain when sitting [58]. In 1995 Allen published a microsurgical breast reconstruction using a free gluteal perforator flap with longer vascular pedicle and without sacrificing the muscle: the superior gluteal artery perforator (SGAP) flap [59]. In 2004 the same team published their experience with 142 gluteal artery perforator flaps, including 6 cases of an inferior gluteal artery perforator (IGAP) flap, which was until then not yet reported for breast reconstruction. The IGAP flap was abandoned early in their series due to the morbidity related to the sciatic nerve. The donor site scar of the SGAP flap is well hidden, but an important disadvantage is contour deformity of the buttocks, especially in oblique oriented designs [60]. In general, redundant gluteal adiposity in a patient, made the SGAP the first choice flap for many years when the abdominal donor site was not available. Nevertheless, the gluteal flaps have several shortcomings: They are challenging to dissect, have a short vascular pedicle, are more difficult to shape since the gluteal fat tends to be more rigid and the scar can result in a contour distortion of the buttocks [61]. In 2007, Papp published the first report of an alternative free flap of the inferior gluteal region based on the descending branch of the inferior gluteal artery that accompanies the posterior femoral cutaneous nerve and emerges from under the edge of the gluteus maximus muscle. This flap, which is called the fasciocutaneous infragluteal (FCI) flap, can easily be harvested as an neurovascular flap by adding branches of the posterior femoral cutaneous nerve and has a long pedicle of up to 18cm. However, sensory changes to the donor site were present in 68% of patients [62]. Because of the abovementioned shortcomings related to gluteal flaps microsurgeons started exploring other donor sites (Table 2.3).

60 The evolution of breast reconstructions with free flaps

Table 2.3. History of the gluteal and lower back as donor sites in breast reconstruction: 1976 The first report of free tissue transfer to reconstruct the postmastectomy defect was with a superior gluteal myocutaneous free flap – Fujino et al. [11] 1989 Description of the inferior gluteal myocutaneous free flap in breast reconstruction – Paletta et al. [58] 1995 Description of the SGAP flap in breast reconstruction – Allen et al. [59] 2003 Report of the LAP flap to reconstruct the breast – de Weerd et al.[75] 2004 Description of the IGAP flap in breast reconstruction – Guerra et al. [60] 2007 First report of the FCI flap in breast reconstruction – Papp et al. [62] Abbreviations: SGAP = superior gluteal artery perforator, LAP = lumbar artery perforator, IGAP = inferior gluteal artery perforator, FCI = fasciocutaneous infragluteal.

2.6. Thigh flaps

Medial thigh

Yousif et al. were the first to describe the medial thigh as donor site for breast reconstruction using a free musculocutaneous gracilis flap with transverse-oriented skin island in 1992. They discovered during cadaver dissections that perforators from the gracilis pedicle had a tendency to travel in a transverse direction, resulting in a transverse clinical territory in the upper inner thigh. They described a single case of breast reconstruction with this free flap. For the microvascular anastomosis to the axillary artery and vein a vein graft was used [63]. The use of this transverse myocutaneous gracilis (TMG) or transverse upper gracilis (TUG) flap in reconstructive breast surgery was further refined by Wechselberger and Schoeller in 2004 and 2011. It is considered a valuable alternative for breast reconstruction after skin-sparing mastectomy in patients with small to moderate sized breasts and unavailable abdominal tissue. Flap harvest is fast and easy, since this is not a perforator flap. Reported donor site morbidity was minimal and is similar to a classical medial thigh lift [64, 65]. Donor site complications of 60 percent are reported, mostly sensory disturbances and wound dehiscence. Aggressive tissue harvest can lead to lymphedema and labial spreading. Conservative tissue harvest is paramount to avoid these complications and flap width should not exceed 8 cm [66, 67]. Modifying the design of the skin island avoids many donor site complications. Despite the known perfusion related complications of the distal third of the skin along the axis of the gracilis muscle, Park et al. renewed the interest for using a vertical designed skin island, known as the vertical upper gracilis (VUG) flap. They also describe the possibility to use bilateral stacked flaps (BUG) for reconstruction of larger breasts [68]. Dayan described in

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2013 the diagonal upper gracilis flap (DUG), a modification of the TUG flap whereby the skin island is oriented along the line of least tension (Langer’s lines). Compared to the VUG flap, the distal third is more reliable since it is closer to the clinical territory of the gracilis pedicle [69].

Posterior thigh

The use of the posterior thigh as donor site for autologous breast reconstruction was introduced in 2012 by Allen et al. They were the first to use the profunda artery perforator (PAP) flap for breast reconstruction. This flap is the perforator version of the posterior thigh myocutaneous flap used to reconstruct pressure sores. It is based on a perforator of the deep femoral vessels (profunda femoris artery and vein) coursing through the adductor magnus muscle. Advantages compared to the TUG/TMG flap are a longer pedicle, sparing the muscles and orienting the skin island away from the lymph nodes in the femoral triangle. Disadvantages are related to the transverse orientation of the flap [70].

Lateral thigh

Already in 1990, Elliott used the lateral transverse thigh free flap as an alternative flap for autologous breast reconstruction in women with excess of fat in the upper lateral thigh or saddlebag deformity [71]. It was later refined to a perforator flap in 2011 by Kind [72]. Hereafter, the flap was further elaborated by Tuinder and renamed septocutaneous tensor fascia latae (sc-TFL) flap or lateral thigh perforator (LTP) flap. Due to excellent results this flap is second choice after the DIEP flap in their department [73]. Also the anterolateral thigh (ALT) flap, a workhorse flap in soft tissue reconstruction, was applied for reconstruction of the post mastectomy defect and first described by Wei [74]. But because of conspicuous scarring and limited bulk it was never popularized for this indication (Table 2.4).

Lower back

The newest donor site in the armamentarium of the reconstructive breast microsurgeon is the lower back. In 2003 de Weerd was the first to present breast reconstruction with a lumbar artery perforator (LAP)-flap [75]. Refinements of the technique were made and published by Opsomer. The most important advantages are the texture of the lumbar fat, which is softer compared to gluteal fat making the shaping much easier, and the

62 The evolution of breast reconstructions with free flaps

Table 2.4. History of the thigh as donor site in breast reconstruction: 1990 First communication of the lateral transverse thigh free flap for autologous breast reconstruction - Elliott et al. [71] 1992 First report of the medial thigh as donor site in breast reconstruction by free musculocutaneous gracilis flap - Yousif et al.[63]

2004 Popularisation of TMG/TUG flap in breast reconstruction - Wechselberger et al. [64] 2012 Description of PAP flap in breast reconstruction - Allen et al. [70] 2013 Description of a diagonal oriented gracilis free flap or DUG flap - Dayan et al.[69] 2018 Description the sc-TFL or LTP flap in breast reconstruction - Tuinder et al.[73] Abbreviations: TMG = transverse myocutaneous gracilis, TUG = transverse upper gracilis, PAP = profunda artery perforator, DUG = diagonal upper gracilis, sc-TFL = septocutaneous tensor fascia latae, LTP = lateral thigh perforator

minimal contour defect despite of large harvested flaps. The major down- side with this flap is the very short pedicle which routinely requires in- terposition grafts. In Ghent the LAP flap turned into the favorite second- choice flap for autologous breast reconstruction [76].

2.7. Future of breast reconstructions

There has been a tremendous and successful progress in reducing do- nor site morbidity in breast reconstructions with free flaps over the past decades. We believe the aesthetic outcome of breast reconstructions will further improve and the donor site morbidity will further diminish in the next years. Tissue regeneration is actively researched to create autologous, tissue engineered, 3D composite tissues. The creation of these tissues could open a whole new era of tissue transplantation without donor site morbidity.

2.8. Conclusion

Women confronted with mastectomy after breast cancer have many options when considering an autologous breast reconstruction. A multidisciplinary surgical approach resulted in in an exponential growth in breast reconstruction possibilities. A reconstructed breast should appear and feel realistic using reconstructive surgery with minimal donor site morbidity and low-risk surgery. Microsurgical breast reconstruction with perforator

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flaps offers reliable, durable and aesthetically pleasing reconstructions, with minimal functional donor site morbidity. The abdominal donor site with the DIEP flap remains the workhorse for the reconstructive microsurgeons, offering a reliable flap with a good donor site morbidity and pleasing aesthetical outcome. Careful patient selection, surgical planning and technical execution are essential to success of the surgical treatment. When the abdomen is not available the thigh flaps (TMG/TUG/PAP) are useful as a second choice. The flaps from gluteal region can be used as a lifeboat. The use of CT scan helps the microvascular surgeon to select the perforator with best vascularization. DIRT is a novel technique which has to potential to contribute to minimize complications and improve outcomes in the future.

64 The evolution of breast reconstructions with free flaps

2.9. References

1. World Cancer Research Fund AifCR. Breast Cancer statistics. In; 2019 2. De Angelis R, Sant M, Coleman MP et al. Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE--5-a population-based study. Lancet Oncol 2014; 15: 23-34. doi:10.1016/s1470-2045(13)70546-1 3. Thiessen FEF, Tjalma WAA, Tondu T. Breast reconstruction after breast conservation therapy for breast cancer. Eur J Obstet Gynecol Reprod Biol 2018; 230: 233-238. doi:10.1016/j. ejogrb.2018.03.049 4. Tondu T, Tjalma WAA, Thiessen FEF. Breast reconstruction after mastectomy. Eur J Obstet Gy- necol Reprod Biol 2018; 230: 228-232. doi:10.1016/j.ejogrb.2018.04.016 5. Verneuil AA. Memoires de Chirurgie. Paris: G. Masson; 1887 6. Rozen WM, Rajkomar AK, Anavekar NS et al. Post-mastectomy breast reconstruction: a history in evolution. Clin Breast Cancer 2009; 9: 145-154. doi:10.3816/CBC.2009.n.024 7. Goldwyn RM. Vincenz Czerny and the beginnings of breast reconstruction. Plast Reconstr Surg 1978; 61: 673-681. doi:10.1097/00006534-197805000-00003 8. Champaneria MC, Wong WW, Hill ME et al. The evolution of breast reconstruction: a historical perspective. World J Surg 2012; 36: 730-742. doi:10.1007/s00268-012-1450-2 9. Mavrogenis AF, Markatos K, Saranteas T et al. The history of microsurgery. Eur J Orthop Surg Traumatol 2019; 29: 247-254. doi:10.1007/s00590-019-02378-7 10. Fujino T, Harasina T, Aoyagi F. Reconstruction for aplasia of the breast and pectoral region by microvascular transfer of a free flap from the buttock. Plast Reconstr Surg 1975; 56: 178-181. doi:10.1097/00006534-197508000-00010 11. Fujino T, Harashina T, Enomoto K. Primary breast reconstruction after a standard radical mastectomy by a free flap transfer. Case report. Plast Reconstr Surg 1976; 58: 371-374. doi:10.1097/00006534-197609000-00028 12. Serafin D, Georgiade NG. Transfer of free flaps to provide well-vascularized, thick cover for breast reconstructions after radical mastectomy. Plast Reconstr Surg 1978; 62: 527-536. doi:10.1097/00006534-197810000-00005 13. Holmstrom H. The free abdominoplasty flap and its use in breast reconstruction. An experimental study and clinical case report. Scand J Plast Reconstr Surg 1979; 13: 423-427 14. Gillies HD, Millard DR. The principles and art of plastic surgery. London: Butterworth; 1957 15. Robbins TH. Rectus abdominis myocutaneous flap for breast reconstruction. Aust N Z J Surg 1979; 49: 527-530. doi:10.1111/j.1445-2197.1979.tb05869.x 16. Hartrampf CR, Scheflan M, Black PW. Breast reconstruction with a transverse abdominal island flap. Plast Reconstr Surg 1982; 69: 216-225. doi:10.1097/00006534-198202000-00006 17. Scheflan M, Dinner MI. The transverse abdominal island flap: part I. Indications, contraindications, results, and complications. Ann Plast Surg 1983; 10: 24-35. doi:10.1097/00000637- 198301000-00005

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18. Boyd JB, Taylor GI, Corlett R. The vascular territories of the superior epigastric and the deep inferior epigastric systems. Plast Reconstr Surg 1984; 73: 1-16. doi:10.1097/00006534- 198401000-00001 19. Friedman RJ, Argenta LC, Anderson R. Deep inferior epigastric free flap for breast reconstruction after radical mastectomy. Plast Reconstr Surg 1985; 76: 455-460. doi:10.1097/00006534- 198509000-00025 20. Arnez ZM, Smith RW, Eder E et al. Breast reconstruction by the free lower transverse rectus abdominis musculocutaneous flap. Br J Plast Surg 1988; 41: 500-505. doi:10.1016/0007- 1226(88)90007-0 21. Grotting JC, Urist MM, Maddox WA et al. Conventional TRAM flap versus free microsurgical TRAM flap for immediate breast reconstruction. Plast Reconstr Surg 1989; 83: 828-841; discussion 842-824. doi:10.1097/00006534-198905000-00009 22. Kroll SS, Rosenfield L. Perforator-based flaps for low posterior midline defects. Plast Reconstr Surg 1988; 81: 561-566. doi:10.1097/00006534-198804000-00012 23. Koshima I, Soeda S. Inferior epigastric artery skin flaps without rectus abdominis muscle. Br J Plast Surg 1989; 42: 645-648. doi:10.1016/0007-1226(89)90075-1 24. Saint-Cyr M, Schaverien MV, Rohrich RJ. Perforator flaps: history, controversies, physiology, anatomy, and use in reconstruction. Plast Reconstr Surg 2009; 123: 132e-145e. doi:10.1097/ PRS.0b013e31819f2c6a 25. Allen RJ, Treece P. Deep inferior epigastric perforator flap for breast reconstruction. Ann Plast Surg 1994; 32: 32-38. doi:10.1097/00000637-199401000-00007 26. Blondeel PN, Boeckx WD. Refinements in free flap breast reconstruction: the free bilateral deep inferior epigastric perforator flap anastomosed to the internal mammary artery. Br J Plast Surg 1994; 47: 495-501. doi:10.1016/0007-1226(94)90033-7 27. Blondeel N, Vanderstraeten GG, Monstrey SJ et al. The donor site morbidity of free DIEP flaps and free TRAM flaps for breast reconstruction. Br J Plast Surg 1997; 50: 322-330. doi:10.1016/ s0007-1226(97)90540-3 28. Grotting JC. The free abdominoplasty flap for immediate breast reconstruction. Ann Plast Surg 1991; 27: 351-354. doi:10.1097/00000637-199110000-00011 29. Arnez ZM, Khan U, Pogorelec D et al. Breast reconstruction using the free superficial inferior epigastric artery (SIEA) flap. Br J Plast Surg 1999; 52: 276-279. doi:10.1054/bjps.1999.3100 30. Hartrampf CR, Jr., Noel RT, Drazan L et al. Ruben's fat pad for breast reconstruction: a peri-iliac soft-tissue free flap. Plast Reconstr Surg 1994; 93: 402-407. doi:10.1097/00006534-199402000- 00030 31. Elliott LF, Hartrampf CR, Jr. The Rubens flap. The deep circumflex iliac artery flap. Clin Plast Surg 1998; 25: 283-291 32. Buchel E. First Report and case series of the perforator DCIA flap for breast reconstruction. Scientific paper session: breast ASRM meeting in 2015 Bahamas; 27-1-2015; 2015; 33. Hamdi M, Weiler-Mithoff EM, Webster MH. Deep inferior epigastric perforator flap in breast reconstruction: experience with the first 50 flaps. Plast Reconstr Surg 1999; 103: 86-95. doi:10.1097/00006534-199901000-00015

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34. Blondeel PN. One hundred free DIEP flap breast reconstructions: a personal experience. Br J Plast Surg 1999; 52: 104-111. doi:10.1054/bjps.1998.3033 35. Keller A. The deep inferior epigastric perforator free flap for breast reconstruction. Ann Plast Surg 2001; 46: 474-479; discussion 479-480. doi:10.1097/00000637-200105000-00003 36. Nahabedian MY, Momen B, Galdino G et al. Breast Reconstruction with the free TRAM or DIEP flap: patient selection, choice of flap, and outcome. Plast Reconstr Surg 2002; 110: 466-475; discussion 476-467. doi:10.1097/00006534-200208000-00015 37. Kroll SS. Fat necrosis in free transverse rectus abdominis myocutaneous and deep inferior epigastric perforator flaps. Plast Reconstr Surg 2000; 106: 576-583. doi:10.1097/00006534- 200009030-00008 38. Blondeel PN, Arnstein M, Verstraete K et al. Venous congestion and blood flow in free transverse rectus abdominis myocutaneous and deep inferior epigastric perforator flaps. Plast Reconstr Surg 2000; 106: 1295-1299. doi:10.1097/00006534-200011000-00009 39. Dancey A, Blondeel PN. Technical tips for safe perforator vessel dissection applicable to all perforator flaps. Clin Plast Surg 2010; 37: 593-606, xi-vi. doi:10.1016/j.cps.2010.06.008 40. Mohan AT, Saint-Cyr M. Advances in imaging technologies for planning breast reconstruction. Gland Surg 2016; 5: 242-254. doi:10.3978/j.issn.2227-684X.2016.01.03 41. Nahabedian MY. Overview of perforator imaging and flap perfusion technologies. Clin Plast Surg 2011; 38: 165-174. doi:10.1016/j.cps.2011.03.005 42. Thiessen FEF, Tondu T, Cloostermans B et al. Dynamic InfraRed Thermography (DIRT) in DIEP- flap breast reconstruction: A review of the literature. Eur J Obstet Gynecol Reprod Biol 2019; 242: 47-55. doi:10.1016/j.ejogrb.2019.08.008 43. de Weerd L, Mercer JB, Weum S. Dynamic infrared thermography. Clin Plast Surg 2011; 38: 277- 292. doi:10.1016/j.cps.2011.03.013 44. Muntean MV, Strilciuc S, Ardelean F et al. Using dynamic infrared thermography to optimize color Doppler ultrasound mapping of cutaneous perforators. Med Ultrason 2015; 17: 503-508. doi:10.11152/mu.2013.2066.174.dyn 45. Tenorio X, Mahajan AL, Elias B et al. Locating perforator vessels by dynamic infrared imaging and flow Doppler with no thermal cold challenge. Ann Plast Surg 2011; 67: 143-146. doi:10.1097/SAP.0b013e3181ef6da3 46. de Weerd L, Weum S, Mercer JB. The value of dynamic infrared thermography (DIRT) in perfora- torselection and planning of free DIEP flaps. Ann Plast Surg 2009; 63: 274-279. doi:10.1097/ SAP.0b013e3181b597d8 47. Giunta RE, Geisweid A, Feller AM. The value of preoperative Doppler sonography for planning free perforator flaps. Plast Reconstr Surg 2000; 105: 2381-2386. doi:10.1097/00006534- 200006000-00011 48. de Weerd L, Mercer JB, Setsa LB. Intraoperative dynamic infrared thermography and free-flap surgery. Ann Plast Surg 2006; 57: 279-284. doi:10.1097/01.sap.0000218579.17185.c9 49. de Weerd L, Miland AO, Mercer JB. Perfusion dynamics of free DIEP and SIEA flaps during the first postoperative week monitored with dynamic infrared thermography. Ann Plast Surg 2009; 62: 42-47. doi:10.1097/SAP.0b013e3181776374

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50. Weum S, Mercer JB, de Weerd L. Evaluation of dynamic infrared thermography as an alternative to CT angiography for perforator mapping in breast reconstruction: a clinical study. BMC Med Imaging 2016; 16: 43. doi:10.1186/s12880-016-0144-x 51. Weum S, Lott A, de Weerd L. Detection of Perforators Using Smartphone Thermal Imaging. Plast Reconstr Surg 2016; 138: 938e-940e. doi:10.1097/prs.0000000000002718 52. Whitaker IS, Lie KH, Rozen WM et al. Dynamic infrared thermography for the preoperative planning of microsurgical breast reconstruction: a comparison with CTA. J Plast Reconstr Aesthet Surg 2012; 65: 130-132. doi:10.1016/j.bjps.2011.07.016 53. John HE, Niumsawatt V, Rozen WM et al. Clinical applications of dynamic infrared thermography in plastic surgery: a systematic review. Gland Surg 2016; 5: 122-132. doi:10.3978/j. issn.2227-684X.2015.11.07 54. Li K, Zhang Z, Nicoli F et al. Application of Indocyanine Green in Flap Surgery: A Systematic Review. J Reconstr Microsurg 2018; 34: 77-86. doi:10.1055/s-0037-1606536 55. Patel NG, Ramakrishnan V. Microsurgical Tissue Transfer in Breast Reconstruction. Clin Plast Surg 2017; 44: 345-359. doi:10.1016/j.cps.2016.12.002 56. Le-Quang C. [Secondary microsurgical reconstruction of the breast and free inferior gluteal flap]. Ann Chir Plast Esthet 1992; 37: 723-741 57. Shaw WW. Breast reconstruction by superior gluteal microvascular free flaps without silicone implants. Plast Reconstr Surg 1983; 72: 490-501. doi:10.1097/00006534-198310000-00013 58. Paletta CE, Bostwick J, 3rd, Nahai F. The inferior gluteal free flap in breast reconstruction. Plast Reconstr Surg 1989; 84: 875-883; discussion 884-875 59. Allen RJ, Tucker C, Jr. Superior gluteal artery perforator free flap for breast reconstruction. Plast Reconstr Surg 1995; 95: 1207-1212. doi:10.1097/00006534-199506000-00010 60. Guerra AB, Metzinger SE, Bidros RS et al. Breast reconstruction with gluteal artery perforator (GAP) flaps: a critical analysis of 142 cases. Ann Plast Surg 2004; 52: 118-125. doi:10.1097/01. sap.0000095437.43805.d1 61. Opsomer D, van Landuyt K. Indications and Controversies for Nonabdominally-Based Com- plete Autologous Tissue Breast Reconstruction. Clin Plast Surg 2018; 45: 93-100. doi:10.1016/j. cps.2017.08.012 62. Papp C, Windhofer C, Gruber S. Breast reconstruction with the fasciocutaneous infragluteal free flap (FCI). Ann Plast Surg 2007; 58: 131-136. doi:10.1097/01.sap.0000237635.05337.a1 63. Yousif NJ, Matloub HS, Kolachalam R et al. The transverse gracilis musculocutaneous flap. Ann Plast Surg 1992; 29: 482-490. doi:10.1097/00000637-199212000-00002 64. Wechselberger G, Schoeller T. The transverse myocutaneous gracilis free flap: a valuable tissue source in autologous breast reconstruction. Plast Reconstr Surg 2004; 114: 69-73. doi:10.1097/01.prs.0000127797.62020.d4 65. Pulzl P, Schoeller T, Kleewein K et al. Donor-site morbidity of the transverse musculocutaneous gracilis flap in autologous breast reconstruction: short-term and long-term results. Plast Recon- str Surg 2011; 128: 233e-242e. doi:10.1097/PRS.0b013e3182268a99

68 The evolution of breast reconstructions with free flaps

66. Locke MB, Zhong T, Mureau MA et al. Tug 'O' war: challenges of transverse upper gracilis (TUG) myocutaneous free flap breast reconstruction. J Plast Reconstr Aesthet Surg 2012; 65: 1041- 1050. doi:10.1016/j.bjps.2012.02.020 67. Craggs B, Vanmierlo B, Zeltzer A et al. Donor-site morbidity following harvest of the transverse myocutaneous gracilis flap for breast reconstruction. Plast Reconstr Surg 2014; 134: 682e-691e. doi:10.1097/prs.0000000000000612 68. Park JE, Alkureishi LW, Song DH. TUGs into VUGs and Friendly BUGs: Transforming the Gracilis Territory into the Best Secondary Breast Reconstructive Option. Plast Reconstr Surg 2015; 136: 447-454. doi:10.1097/prs.0000000000001557 69. Dayan E, Smith ML, Sultan MR et al. The Diagonal Upper Gracilis (DUG) Flap: A Safe and Improved Alternative to the TUG flap. Plast Reconstr Surg October 2013; 132: 33-34. doi:10.1097/01.prs.0000435901.60333.62 70. Allen RJ, Haddock NT, Ahn CY et al. Breast reconstruction with the profunda artery perforator flap. Plast Reconstr Surg 2012; 129: 16e-23e. doi:10.1097/PRS.0b013e3182363d9f 71. Elliott LF, Beegle PH, Hartrampf CR, Jr. The lateral transverse thigh free flap: an alternative for autogenous-tissue breast reconstruction. Plast Reconstr Surg 1990; 85: 169-178; discussion 179-181 72. Kind GM, Foster RD. Breast reconstruction using the lateral femoral circumflex artery perforator flap. J Reconstr Microsurg 2011; 27: 427-432. doi:10.1055/s-0031-1281527 73. Tuinder SMH, Beugels J, Lataster A et al. The Lateral Thigh Perforator Flap for Autologous Breast Reconstruction: A Prospective Analysis of 138 Flaps. Plast Reconstr Surg 2018; 141: 257-268. doi:10.1097/prs.0000000000004072 74. Wei FC, Suominen S, Cheng MH et al. Anterolateral thigh flap for postmastectomy breast reconstruction. Plast Reconstr Surg 2002; 110: 82-88. doi:10.1097/00006534-200207000-00015 75. de Weerd L, Elvenes OP, Strandenes E et al. Autologous breast reconstruction with a free lumbar artery perforator flap. Br J Plast Surg 2003; 56: 180-183. doi:10.1016/s0007- 1226(03)00039-0 76. Opsomer D, Stillaert F, Blondeel P et al. The Lumbar Artery Perforator Flap in Autologous Breast Reconstruction: Initial Experience with 100 Cases. Plast Reconstr Surg 2018; 142: 1e-8e. doi:10.1097/prs.0000000000004522

Chapter 3

Dynamic infrared thermography (DIRT) in DIEP-flap breast reconstruction: a review of the literature

This chapter has been published as: Filip Thiessen, Thierry Tondu, Ben Cloostermans, Yarince Dirkx, Dorien Auman, Stefaan Cox, Veronique Verhoeven, Guy Hubens, Gunther Steenackers, Wiebren Tjalma. Dynamic infrared thermography (DIRT) in DIEP-flap breast reconstruction: a review of the literature. European Journal of Obstetrics & Gynecology and Reproductive Biology 242 (2019) 47–55. https://doi.org/10.1016/j.ejogrb.2019.08.008 Chapter 3: Contents

Abstract 73 3.1. Introduction 74 3.2. Method 75 Search and study collection 75 Study selection 76 Study quality 76 Data selection 76 3.3. Results 77 3.4. Discussion 85 DIRT in the preoperative phase 86 DIRT in the peroperative phase 87 DIRT in the postoperative phase 87 Limitations 87 3.5. Conclusion 88 3.6. References 89 DIRT in DIEP flap breast reconstruction: a review of the literature

Abstract

In the industrialised world still 34 % of the breast cancer patients are surgically treated by a mastectomy. Breast cancer patients in general have a good prognosis and a long-term survival. Therefore, it is important that the treatment doesn’t focus only on survival but also on the quality of life. Breast reconstruction improves the quality of life. A breast reconstruction with an autologous free DIEP (Deep Inferior Epigastric artery Perforator) flap is one of the preferred options after mastectomy. A challenging step in this procedure is the selection of a suitable perforator that provides sufficient blood supply for the flap. Current techniques to locate the perforator vessels include handheld Doppler, colour Doppler ultrasound (CDU), Mag- netic resonance angiography (MRA), computer tomographic angiography (CTA) and dynamic infrared thermography (DIRT). At present CTA is the golden standard and DIRT a new option. The objective of this article is to document whether DIRT can accurately map the position of the perforators and measure their influence on the perfusion of the flap in order to select the best perforators to improve the outcome of breast reconstructions with free DIEP flaps. A systematic review of the literature published between January 1998 and November 23th 2018 was conducted regarding the possible benefit of dynamic infrared thermography (DIRT) in DIEP-flap breast reconstructions.

The databases PubMed and Web of Science were used to search for qualified articles. Inclusion criteria were women who underwent a breast reconstruction by means of a DIEP flap where DIRT was used to analyse the blood supply of the flap.

The search yielded a total of fourteen suitable articles: six articles being descriptive clinical studies, three case reports, three expert opinions/Overview articles and two systematic reviews.

There are only a limited number of studies looking at the use of DIRT in breast reconstruction with DIEP-flaps. Adequate identification of the dominate vessel(s) in DIEP reconstruction is essential for a successful outcome. DIRT appears to be an ideal alternative technique for the identification of the dominant perforators of the flap. With the use of DIRT it is possible to identify the dominant vessel(s) preoperatively. The use of DIRT during the operation allows the tailoring of the surgery and postoperative use may identify vascularisation problems in an early stage.

Additional high-quality studies are needed, but DIRT seems to be a valuable investigation for the pre-, per- and postoperative phase of DIEP-flap reconstructions.

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3.1. Introduction

reast cancer is the most frequent cancer among women. At present, breast cancer impacts 2.1 million women worldwide each year [1]. It is suspected that this figure will increase further to 3.0 million women in 2040 [1]. BBreast cancer causes the highest number of cancer-related deaths among women. In 2018, it is estimated that approximately 627,000 women died from breast cancer – that is approximately 15% of all cancer deaths among women. While breast cancer rates are higher among women in more developed regions, rates are increasing in nearly every region glob- ally [1]. Belgium has the highest incidence of breast cancer in women per capita (113.2/100,000) which totals to around 11,000 women each year [1]. One third (34%) of the breast cancer patients undergo uni- or bilateral mastectomy and 1 out of 7 undergo reconstruction surgery. Half of which performed with autologous tissue. Thirty two percent of the autologous tissue flaps are deep inferior epigastric perforator (DIEP)-flaps [1,2]. In a breast reconstruction with a DIEP flap, the skin and subcutaneous tissue from the patient’s lower abdomen are used as a free flap to reconstruct the patient’s breast. The flap receives its blood supply from the deep inferior epigastric artery and one or two concomitant veins through a perforator. The perforator is then anastomosed to the internal mammary artery and vein for an optimal blood supply of the reconstructed breast [3–6]. Selection of the best perforators is the key in this procedure. This will reduce operative time, lower complication rates and ensure an overall better result [7]. Current techniques to locate the perforator vessels include handheld Doppler, colour Doppler ultrasound (CDU), Magnetic resonance angiography (MRA), computer tomographic angiography (CTA) and dynamic infrared thermography (DIRT) [7–9]. The current golden standard for perforator selection is CTA on which the location and hemodynamic properties of the flap can be reviewed [4,7,8,10]. CTA is frequently used because it is non-invasive and has a high spatial resolution with visualisation of the intramuscular course of the vessels even as small as 0.3 mm. This technique however also has some clear disadvantages: use of intravenous (IV) contrast agents and radiation, high purchasing cost, not usable during surgery and it also does not provide physiological information on flow characteristics of perforators pre- and postoperatively. An alternative might be DIRT (dynamic infrared thermography). DIRT

74 DIRT in DIEP flap breast reconstruction: a review of the literature

uses an IR camera to measure the skin temperature based on heat emitted by tissues. This generates a color-coded map, which is a translation for the perfusion of the skin [7,11]. DIRT is a dynamic investigation technique; this means that the skin must undergo a thermal cold challenge. The DIRT measures the rate and patterns of rewarming after cooling. This technique allows to identify the most dominant perforators and the area they perfuse. DIRT is less invasive than CTA because it doesn’t use radiation nor contrast agents. It is a quick imaging technique that is available pre-, per- and post-operative. DIRT is relatively easy to interpret, and it has a low purchasing cost. On the other hand, DIRT only provides information on the physiology of the perforator and not on the morphology. This means that the surgeon must have a thorough knowledge of the vascular anatomy in order to interpret the results [11]. The objective of present systematic review is to document whether DIRT can accurately map the position of the perforators and measure their influence on the perfusion of the DIEP flap in order to improve the outcome of breast reconstructions with free DIEP flaps. Unlike the included reviews, our review focuses not only on the peroperative use of DIRT, but also on the pre-, per- and postoperative use of DIRT in breast reconstructions with DIEP flaps [19, 20]. DIRT will be compared with (multidetector) CTA (MDC- TA), MRA and handheld Doppler or Colour Doppler Ultrasound (CDU).

3.2. Method

Search and study collection

The databases that were consulted for this review were PubMed and Web of Science. The following search terms were used: [thermography AND (breast reconstruction OR mammoplasty)]. Articles that had been published between January 1998 and November 23th 2018 were included. The primary search provided 29 matches in PubMed and 32 in Web of Sci- ence. An extra search in Science Direct and the Cochrane Database delivered no new results. After evaluating the references of the eligible articles, 12 more studies were found. After duplicates were removed, 56 articles were taken into account.

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Study selection

Three independent readers reviewed the selected articles. All articles of conflict were debated until mutual agreement was found. One article was immediately discarded based on the language (Russian). Additionally 40 articles were excluded on title and abstract. The criteria used for the exclusion on title and abstract were: • The article must contain the use of thermography. • The included patients undergo breast reconstruction with DIEP-flap. • The full text of the article is written in English or German. If one of these criteria was not met, the study was excluded. Fourteen studies measured up to all the criteria and were accepted for further analysis.

Study quality

Using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2011 v2.1 the qualified articles were assessed for their level of evidence by three independent reviewers (Table 3.5). Any disparity between them was discussed until both gave their consent.

Data selection

All the selected studies reported the advantages and disadvantages of different imaging methods for the selection of the dominant perforators for DIEP flap breast reconstructions. Present study reviewed the use of DIRT during breast reconstructions with DIEP flaps and compare the results with (multidetector) CTA (MDCTA), MRA and handheld Doppler or Colour Doppler Ultrasound (CDU). The data we extracted from the selected studies are the number of par- ticipants, their mean age and mean BMI, imaging methods preoperatively, peroperatively and postoperatively performed with the accompanying results and the outcome of the surgery.

76 DIRT in DIEP flap breast reconstruction: a review of the literature

3.3. Results

The literature search, performed by previously defined search terms, identified 61 records. After adding 12 studies from references and remov- ing all the duplicates 56 articles remained for screening. The titles and ab- stracts were examined and discussed until 14 articles remained for full text screening. Those studies could be included in the systematic review after full text reading. The process of data collection and selection is shown in Figure 3.1: Prisma flow diagram showing the process of data collection, selection and organisation. In total fourteen studies were included, with six articles being descriptive clinical studies [4, 8, 13, 14, 15, 16], three case reports [12, 17, 18], three expert opinions/Overview articles [9, 10, 11] and two systematic review on intraoperative evaluation of perfusion in free flap surgery [19, 20]. No published randomised controlled studies were found.

Figure 3.1. Prisma 2009 flow diagram. From the PRISMA group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analysis: the PRISMA statement. PLoS Med §(7): e1000097. Doi: 10.1371/journal.pmed1000097.

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Nine studies described the use of DIRT for preoperative imaging [4, 8–14,16], seven studies described the intraoperative use of DIRT [11,14,15,17,18,19,20] and two studies investigated the postoperative use of DIRT [11,14]. Several studies [4,8,11–13,18] concluded that DIRT is a promising technique for preoperative perforator mapping in DIEP-flap reconstructions, because DIRT can identify the location of the perforators and can give a qualitative assessment of the perforators. Although Muntean et al. [7] believe in their study on pigs that DIRT should be combined with CDU for an optimal result. Smit et al. [19] concluded that fluorescence imaging and laser Doppler are the most suitable imaging techniques to measure free flap perfusion peroperatively, but did not comment on the outcome of the use of DIRT peroperatively. De Weerd et al. [15] found that DIRT could be a valuable method for intraoperative monitoring of free tissue transfer. The collected data are summarized in Tables 3.1-7 (Table 3.1: overview of studies describing the advantages and disadvantages of DIRT; Table 3.2: overview of studies describing the advantages and disadvantages of (MD) CTA; Table 3.3: overview of studies describing the advantages and disadvantages of MRA; Table 3.4: overview of studies describing the advantages and disadvantages of Handheld Doppler/CDU; Table 3.5: overview of all included studies with their results and level of evidence; Table 3.6: summary of the advantages and disadvantages of DIRT; Table 3.7: summary of the advantages and disadvantages of (MD)CTA).

78 DIRT in DIEP flap breast reconstruction: a review of the literature

Table 3.1. Overview of studies describing the advantages and disadvantages of DIRT. Study DIRT: advantages DIRT: disadvantages De Weerd et al. Indirect information of the flow 2009 (13) Easy to interpret Non-invasive No radiation No contrast agents Easy to execute Nahabedian et No radiation Moderate accuracy al. 2011 (9) No contrast agents No information on course or calibre of vessel Tenorio et al. Investigate any tissue with outstanding Cold challenge is uncomfortable for the 2011 (8) precision patient Simple procedure Artefact images (due to skin rash, subcuta- Detects clinically significant vessels neous injections…) De Weerd et al. Non-invasive Does not show morphology of the perfora- 2011 (11) No radiation tors No contrast agents Easy to perform Relatively easy to interpret Able to detect reperfusion problems (tor- sion/ external compression) during surgery Immediate feedback Whitaker et al. Repeatable Only detects vessels >1mm diameter 2012 (12) Pre-, intra- and postoperative Temporal information Provides information regarding functional characteristics of individual vessels No radiation Non-invasive Single hospital visit Short procedure Immediate report Low cost Detects clinically significant vessels Lohman et al. Qualitative information Subjective information 2015 (20) facilitates flap design Cold challenges Time consuming Weum et al. No information about intramuscular course 2016 (4) Detects only perforators that transport blood to the skin surface Mohan et al. Non-invasive Limited evidence 2016 (10) No contrast agents Moderate and variable data Low cost 2D images Not widely available Smit et al. 2018 Assessment of perfusion Influence of internal and external factors (19) Fast and easy

Steenackers et Real time image Only the perforators going to the skin will al. 2018 (18) be shown

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Table 3.2. Overview of studies describing the advantages and disadvantages of (MD)CTA. Study (MD)CTA: advantages (MD)CTA: disadvantages De Weerd et al. Information on the diameter and location Radiation 2009 (13) Contrast agents Nahabedian et Precise anatomic localization and intra- IV contrast agents al. 2011 (9) muscular course Radiation Valuable in women who had prior abdomi- No information on the flow of the perfora- nal surgery tor 3D images Tenorio et al. Global picture (trajectory can be obtained) Radiation 2011 (8) IV contrast agents High cost De Weerd et al. High spatial and temporal resolution IV contrast agents 2011 (11) Precise description of origin, intramuscular Radiation course and point of fascia penetration High cost Whitaker et al. Detects 100% of perforators Radiation 2012 (12) Locates to <1mm IV contrast agents 3D images Delay between scan and report Static images High cost Mohan et al. 3D or 4D image Radiation 2016 (10) Ultra high resolution Use of IV contrast agents with the risk of Objective findings hypersensitivity or nephrotoxicity Detects vessels as small as 0.3mm No physiological information on flow char- Easy interpretation acteristics or assessment of perfusion Sensitivity and specificity close to 100% High cost Visualisation of linking vessels, connection with adjacent perforator territories Weum et al. Precise anatomical description of the Often intra-operative changes necessary 2016 (4) origin of perforators, intramuscular course (18) and point of fascia penetration Radiation Information on the continuity of the deep Contrast agents inferior epigastric system in patients that Diameter is sum of artery and vein have been previously operated in that area High cost Time consuming

80 DIRT in DIEP flap breast reconstruction: a review of the literature

Table 3.3. Overview of studies describing the advantages and disadvantages of MRA. Study MRA: advantages MRA: disadvantages Nahabedian et No radiation Contrast agents al. 2011 (9) Greater contrast resolution than CTA Lower spatial resolution than CTA so it can detect very small perforators Motion artefacts due to breath holding periods Information on perforator location, No information on flow size and distance from umbilicus 97% correlation between MRA and intraoperative findings Tenorio et al. Global picture (trajectory can be Use of contrast agents 2011 (8) obtained) Expensive Mohan et al. 3D image Longer scan time 2016 (10) No radiation Need for MR contrast agent (but better safety- High imaging quality and accurate risk profile and lower hypersensitivity than CTA) localization of perforators Contraindications e.g. defibrillator, claustropho- High concordance with intraoperative bia, metallic foreign objects… findings High cost Better delineation of intramuscular Limitation for vessels <0.8mm course Motion artefacts (long breath-hold periods) Availability and timing

Table 3.4. Overview of studies describing the advantages and disadvantages of Handheld Doppler/CDU. Study Handheld Doppler / CDU: advantages Handheld Doppler / CDU: disadvantages De Weerd et al. Many false positive results 2009 (13) Definite learning curve Tenorio et al. Can differentiate between artery and Sensitivity and specificity not accurate enough 2011 (8) vein Unreliable information about dominance of Not expensive perforators Easy to use No information about surface area or perfusion or size of vessel False positive locations (deep blood vessels that do not perfuse skin Examiner-dependent Time consuming Often uncomfortable for the patient Depends on patient’s BMI Nahabedian et Flow, direction and velocity easily No 3D image or architectural detail al. 2011 (9) determined Moderate accuracy Differentiate between vein and artery Many false positive results 96% effective perforator detection No information on calibre or course No radiation No contrast agents Smit J et al. Non invasive Only assessment of pedicle 2018 (19) Simple and consistent method Movement artefact No assessment of perfusion area Mohan et al. Less expensive Significant inter-observer variability 2016 (10) No radiation or contrast agents Long investigation (45-60min) High false positive rates Difficulty in interpretation of findings Difficult reproducibility Patient body habitus dependent Only 2D images

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Table 3.5. Overview of included studies and their results and level of evidence. Study Patient info Preoperative Intraoperative Postoperative Study Design and investigations investigations Investigations / outcome Level of evidence* De Weerd et al. 10 patients Handheld Doppler and DIRT 2 flaps failed: 1 due to 2006 (15) Mean age: 49.5y DIRT In all cases DIRT intima lesion; 1 due to inad- Descriptive clinical (34-59) corresponded with vertent damage study, IV Mean BMI: Doppler 25.3 kg/m2 DIRT detects perfu- (20.2-30.5) sion problems Kalra et al. 2007 2 patients Objective measure- (17) Mean age: 41y ment of perfusion Case report, IV of perforators with DIRT De Weerd et al. 20 patients (16 Handheld Doppler and End of operation: Clinical assessment, hand- 2009 (14) DIEP, 4 SIEA) DIRT DIRT held Doppler, DIRT on day Descriptive clinical Mean age: 1,3 and 6 after surgery study, IV 51y (34-65) DIRT: pattern of general Mean BMI: rewarming + pattern of re- 27.0 kg/m2 warming with hotspots (20.2-30.5) Day 1: hyperaemia All DIEP flaps survived, 5 partial flap loss (<5%) 1 SIEA flap did not survive De Weerd et al. 27 patients DIRT and handheld In all DIEP flaps: All flaps survived, 3 had mi- 2009 (13) (23 DIEP) Doppler (+ last 8 pa- selected hot spot = nor partial flap loss (<5%) Descriptive clinical Mean age: tients: additional CTA) suitable perforator study, IV 50y (34-65) Not all Doppler loca- In all cases: DIRT Mean BMI: tions could be related correlated well with 26.2 kg/m2 to a hot spot CTA and intraopera- (20.2-36.4) Hot spots always tive findings slightly more lateral Tenorio et al. 2011 10 patients Handheld doppler and All perforators (8) DIRT: 33% no match confirmed during Descriptive clinical doppler: deep fascia surgery study, IV level; DIRT: subcutaneous tissue No thermal challenge Nahbedian 2011 (9) MRA, CTA, DIRT, Near Infrared Spectroscopie Expert opinion/ Fluorescent Angio, (NIR) overview, IV Duplex and Color Duplex ultrasound De Weerd et Al. DIRT DIRT DIRT 2011 (11) Expert opinion/ overview, IV Whitaker et al. 2012 1 patient, CTA : one suitable Confirmation per- No complications (12) 41y single medial row forator Case report, IV perforator (2mm) DIRT: one hot spot

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Table 3.5. Continued Study Patient info Preoperative Intraoperative Postoperative Study Design and investigations investigations Investigations / outcome Level of evidence* Lohman et al. 2015 DIRT; Indocyanine (20) green angiography; Systematic review Photospectrometry: and Meta-analysis, I potential benefit, but more studies needed Weum et al. 2016 25 patients Doppler, CTA, DIRT 24/25 flaps survived, 1 flap: (4) Mean age: 57y DIRT bleeding (diagnosed to late) Descriptive clinical (38-69) In all cases: DIRT selected study, IV Mean BMI: most suitable perforator 27.2 kg/m2 (21.6-32.4) Mohan AT et al. CTA, MRA, DIRT, indo- 2016 (10) cyanine green fluores- Expert opinion/ cence angiography overview, IV Walle et al. 2017 10 patients, CTA, DIRT All perforators (16) (13 DIEP) confirmed during Descriptive clinical Mean age: 55y surgery study, IV Mean BMI: 26 kg/m2 Steenackers G et al. CTA, DIRT CTA, DIRT 2018 (18) Case report, IV Smit JM et al. 2018 Fluorescence imag- (19) ing, laser Doppler, Systematic review oxygen saturation, and Meta-analysis, I ultrasound, DIRT * Oxford Centre for Evidence-Based Medicine 2011

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Table 3.6. Summary of the advantages and disadvantages of DIRT. Advantages Number of studies According studies Non-invasive 5 (9-13) No contrast agents 5 (9-11,13,20) No radiation 3 (11-13) Low cost 3 (10,12,20) Repeatable 1 (12) Pre-, intra- and postoperative use 1 (12) Information on flow and functional characteristics of the vessels 4 (8,9,12,13) (e.g. diameter) Requires single hospital visit 1 (12) Short procedure 2 (12,18) Real-time and immediate report 3 (11,12,18) Identifies clinically significant vessels 1 (12) Simple investigation (easy to perform, easy to interpret) 5 (8,11,13,18,20) Investigate any tissue with outstanding precision 1 (8) Shows reperfusion problems during surgery 1 (11) Disadvantages Number of studies According studies No information on intramuscular course of the vessels 1 (4) Detects only perforators that transport blood to the skin surface 2 (4,18) Limited evidence (moderate and variable data) 3 (10,19,20) 2D images 1 (10) Low availability 1 (10) Detects only perforators with diameter >1mm 1 (12) Temporal information 1 (12) No information on the morphology of the vessels 2 (9,11) Cold challenge is uncomfortable for patient 2 (8,20) Artefact images 2 (8,19) Moderate accuracy 1 (9)

Table 3.7. Summary of the advantages and disadvantages of (MD)CTA. Advantages Number of studies According studies Precise anatomical description of the origin of perforators, intra- 4 (4,9,11,13) muscular course and point of fascia penetration Information on the continuity of the deep inferior epigastric sys- 2 (4,9) tem in patients that have been previously operated in that area 3D or 4D images 3 (9,10,12) Objective findings 1 (10) Detects vessels as small as 0,3mm 2 (10,12) High spatial and temporal resolution 2 (10,11) Easy interpretation 1 (10) Global picture 1 (8) Detects close to 100% of perforators 2 (10,12) Visualisation of linking vessels, connection with adjacent perfo- 1 (10) rator territories Disadvantages Number of studies According studies Often fails to identify dominant perforator because the diameter 1 (4) is the sum of artery and vein High cost 5 (4,8,10,11,12) Radiation 7 (4,8,9,10,11,12,13) IV contrast agents 7 (4,8,9,10,11,12,13) No physiological information on flow characteristics or assess- 2 (9,10) ment of perfusion Delay between scan and report 1 (12) Static images 1 (12) Time consuming investigation 1 (4)

84 DIRT in DIEP flap breast reconstruction: a review of the literature

3.4. Discussion

Breast reconstruction after breast cancer with a free DIEP flap is one of the most preferred reconstructive techniques in Western Europe at the moment. Unlike breast reconstructions with the free transverse rectus abdominis myocutaneous flap, no muscle of fascia is harvested in breast reconstructions with the DIEP flap, in order to reduce the donor side morbidity [21]. In a free transverse rectus abdominis myocutaneous flap several perforators supply the flap, while a free DIEP flap is only supplied by 1 or 2 perforators. The selected perforator is crucial for flap survival as it is the only source of blood supply to the flap. Therefore adequate perforator selection is mandatory for this type of surgery. Perforator flap surgery requires dissection of small and fragile blood vessels. The pre-operative identification and mapping of the perforators is necessary to reduce complications and optimizes flap design, reduces operating times, lowers complication rates and provides and overall better result [22]. Currently, CTA is considered to be the golden standard for preoperative perforator selection [4,7,8,10]. CTA allows for precise anatomical description of the origin of the perforators, their intramuscular course and the point of fascia penetration. However, CTA has some clear disadvantages: the use of IV contrast agents, radiation exposure and the high purchasing cost [4,7–13,23]. Therefore, an alternative was sought. Dynamic infrared thermography (DIRT) is an attractive approach for perforator mapping in DIEP flaps with lesser disadvantages. Itoh and Arai described for the first time in 1993 the use of dynamic infrared thermography (DIRT) for perforator mapping in DIEP flaps [24]. DIRT uses an IR camera to measure the skin temperature based on heat emitted by tissues. This generates a color-coded map, which is a translation for the perfusion of the skin [7,11]. As the name implies, DIRT is a dynamic investigation technique. This is because the skin must undergo a thermal cold challenge first. DIRT measures the rate and pattern of rewarming after cooling. Our review showed that DIRT is a promising technique to support and even replace CTA because DIRT doesn’t need IV contrast agents nor radiation. It is therefore a safe, repeatable and easy investigation. Together with the fact that it is a short investigation that requires only a single hospital visit, it results in a high patient compliance. In addition, this technique has a low cost, is easy to perform and easy to interpret for the surgeon. On the other hand, DIRT produces 2D images that only provide information on the physiology of the vessels and not on the morphology [7–13,18]. About the accuracy of this technique is not enough evidence yet [10].

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When we study the results of the advantages and disadvantages of the different imaging methods, we can conclude that the golden standard CTA has a very high resolution to give a precise anatomical description of the origin of perforators, their intramuscular course and their point of fascia penetration (Table 3.2 and 7). The 3D image makes it easy to interpret the results. Another advantage is that it can be used in women that have been previously operated in the abdominal area. Unfortunately, CTA is an expensive imaging technique that uses radiation and IV contrast agents. It also provides no physiological information of the perforators and often has a false positive result when not compared to another imaging method, because the diameter of a vessel is the sum of the artery and vein [4,7]. MRA is also a technique with need of IV contrast agents and a major limitation are the motion artefacts and the long breath-hold periods (Table 3.3). It has a slightly lower spatial resolution than CTA and provides no information on the flow of the perforators. It has however a greater contrast resolution than CTA and has a good correlation with intraoperative findings [8–10]. Doppler (Table 3.4) is a safe and cheap technique gives information on the course, diameter and blood flow characteristics of the perforator vessels and is able to differentiate between an artery and a vein, but is has to deal with a lower sensitivity and specificity, inter-observer variability and a high number of false positives [7–10,13,25]. Moreover it is a very time consuming examination.

This review revealed that DIRT has more to offer than only preoperatively perforator selection. It can also be used for the peroperative monitoring of the flap perfusion. Additionally it can be used for flap monitoring in order to detect early perfusion problems [11,14,15,18,19,20].

DIRT in the preoperative phase

When DIRT was tested preoperatively in clinical studies, in all cases DIRT selected the dominant perforator for the skin flap, which was confirmed during the surgery [4,7,8,12–17]. Hot spots that show rapid and progressive rewarming can be related to suitable perforators peroperatively. Rapid rewarming indicates that the perforator is capable of transport more blood to the skin, rapid progression of the hot spots suggests a better developed vascular network around the hotspot [11]. DIRT correlated well with CTA, but less with Doppler. This might be because Doppler measures vessels in the deep fascia level and DIRT measure

86 DIRT in DIEP flap breast reconstruction: a review of the literature

vessels in the subcutaneous tissue level.

DIRT in the peroperative phase

DIRT during surgery was used in seven of the included articles [11,14,15,17,18,19,20]. DIRT in the intraoperative phase was able to detect successful arterial inflow in the flap, as well as partial and total obstruction of arterial inflow. DIRT can also measure the profound improvement in rate and pattern of rewarming after performing an extra venous anastomosis [11, 15]. Kalra et al. confirmed during a pilot study on 2 patients that thermography was able to measure the strength of each perforator on the perfusion of the flap [17]. They did not include cooling of the flap. DIRT is a valuable alternative of clinical examination to evaluate at any stage during surgery to check the perfusion of the flap. DIRT also allows for qualitative assessment of the perforators and facilitates flap design [20]. However further studies are needed to confirm and standardize these results.

DIRT in the postoperative phase

Monitoring of the DIEP flap postoperatively is mandatory to detect early signs of compromised perfusion. At present most surgeons rely on clinical observations to monitor flap perfusion. These clinical observations include skin color, turgor of the flap, capillary refill and skin temperature. In a clinical study with 20 free flaps during the first postoperative week after a free DIEP flap DIRT was used to examine the qualitative changes in perfusion of the flap [14]. The postoperative use of DIRT during the first postoperative week showed that the vascularization of the free DIEP flap is dynamic process. The monitoring postoperative is promising to detect perfusion problems in free DIEP flaps. However additional studies have to be performed to standardize the use of DIRT to detect perfusion problems in free flaps.

Limitations

Nearly all of the articles in this review are descriptive clinical studies [4, 8, 13, 14, 15, 16], case reports [12, 17, 18], expert opinions/Overview articles [9, 10, 11] and only two systematic reviews [19,20]. The level of evidence of these studies is low, which gives reason to believe there is more risk for bias. Also the included group of patients is rather limited with 27 patients included in the biggest series [13]. There were no published ran-

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domised trials on this topic. This limits the quality of evidence presented in this systematic review.

3.5. Conclusion

The level of evidence for DIRT is limited due to the lack of randomized controlled trials. The available data revealed that DIRT is already a valuable asset for preoperatively perforator selection: it is a harmless, low-cost and quick imaging tool that gives information on blood flow and functional characteristics of the vessels. Although it gives no information on the morphology of the vessels and only detects certain perforators (diameter >1mm and those that transport blood to the skin surface), it is capable of identifying the vessels that are clinically significant. Moreover, it is easy to use and delivers easy-to-interpret results in real-time, which makes it useful for intraoperative flap monitoring as well. The authors conclude that preliminary studies are promising on the use of DIRT in DIEP-flap breast reconstruction, but this information is not standardized yet and more studies are recommended. This means that there is still need for further investigations, not only for the pre-operative use of DIRT but also for the per- and postoperative use. Standardisation of the measurement methodology, measurement setup, processing of the images and cooling should be investigated in future clinical studies and even further investigations on animal models should be considered. Although randomized studies are needed to provide definitive proof, the data in these studies suggest that the use of DIRT is an additional tool that improves the results of free flap breast reconstructions and on top of that the examination is cheap, not invasive and does not harm the patient.

88 DIRT in DIEP flap breast reconstruction: a review of the literature

3.6. References

1. cancer WHO-iafro. Estimated age-standardized incidence rates (World) in 2018, all cancers, both sexes, all ages [Internet]. 2018. Available from: http://gco.iarc.fr/today/online-analysis- map?projection=globe (accessed on March 10, 2019) 2. KCE. Borstreconstructie na kanker in drie cijfers [Internet]. 2019. Available from: https://kce. fgov.be/nl/news/borstreconstructie-na-kanker-in-drie-cijfers (accessed on March 10, 2019) 3. Granzow JW, Levine JL, Chiu ES, Allen RJ. Breast reconstruction using perforator flaps. J Surg Oncol. 2006;94(6):441–54. 4. Weum S, Mercer JB, de Weerd L. Evaluation of dynamic infrared thermography as an alternative to CT angiography for perforator mapping in breast reconstruction: A clinical study. BMC Med Imaging [Internet]. 2016;16(1):1–7. Available from: http://dx.doi.org/10.1186/s12880- 016-0144-x 5. Tondu T, Tjalma WAA, Thiessen FEF. Breast reconstruction after mastectomy. Eur J Obs Gynecol Reprod Biol. 2018;230:228–32. 6. Thiessen FEF, Tjalma WAA, Tondu T. Breast reconstruction after breast conservation therapy for breast cancer. Eur J Obs Gynecol Reprod Biol. 2018;230:233–8. 7. Muntean M V., Strilciuc S, Ardelean F, Pestean C, Lacatus R, Badea AF, et al. Using dynamic infrared thermography to optimize color Doppler ultrasound mapping of cutaneous perforators. Med Ultrason. 2015;17(4):503–8. 8. Tenorio X, Mahajan AL, Elias B, van Riempst JS, Wettstein R, Harder Y, et al. Locating perforator vessels by dynamic infrared imaging and flow Doppler with no thermal cold challenge. Ann Plast Surg. 2011;67(2):143–6. 9. Nahabedian MY. Overview of perforator imaging and flap perfusion technologies. Clin Plast Surg. 2011;38(2):165–74. 10. Mohan AT, Saint-Cyr M. Advances in imaging technologies for planning breast reconstruction. Gland Surg. 2016;5(2):242–54. 11. de Weerd L, Mercer JB, Weum S. Dynamic Infrared Thermography. Clin Plast Surg. 2011;38(2):277–92. 12. Whitaker IS, Lie KH, Rozen WM, Chubb D, Ashton MW. Dynamic infrared thermography for the preoperative planning of microsurgical breast reconstruction: A comparison with CTA. J Plast Reconstr Aesthetic Surg. 2012;65(1):130–2. 13. de Weerd L, Weum S, Mercer JB. The value of dynamic infrared thermography (DIRT) in perfora- torselection and planning of free DIEP flaps. Ann Plast Surg. 2009;63(3):274–9. 14. de Weerd L, Miland AO, Mercer JB. Perfusion dynamics of free DIEP and SIEA flaps during the first postoperative week monitored with dynamic infrared thermography. Ann Plast Surg. 2009;62(1):42–7. 15. de Weerd L, Mercer JB, Setsa LB. Intraoperative dynamic infrared thermography and free-flap surgery. Ann Plast Surg. 2006;57(3):279–84. 16. Walle L, Fansa H, Frerichs O. Smartphone-based thermography for perforator localisation in microvascular breast reconstruction. Handchirurgie Mikrochirurgie Plast Chir. 2018;50(2):111–7.

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17. Kalra S, Dancey A, Waters R. Intraoperative selection of dominant perforator vessel in DIEP free flaps based on perfusion strength using digital infrared thermography - a pilot study. J Plast Reconstr Aesthet Surg. 2007;60(12):1365–8. 18. Steenackers G, Peeters J, Parizel P, Tjalma W. Application of passive infrared thermography for DIEP flap breast reconstruction. 14th Quant InfraRed Thermogr Conf. 2018;25–9. 19. Smit JM, Negenborn VL, Jansen SM, Jaspers MEH, de Vries R, Heymans MW, et al. Intraopera- tive evaluation of perfusion in free flap surgery: A systematic review and meta-analysis. Micro- surgery. 2018;38(7):804–18. 20. Lohman RF, Ozturk CN, Ozturk C, Jayaprakash V, Djohan R. An analysis of current techniques used for intraoperative flap evaluation. Ann Plast Surg 2015;75: 679-685 21. Blondeel PN, Vanderstraeten GG, Monstrey SJ, Van Landuyt K, Tonnard P et Al. The donor site morbidity of free DIEP flaps and free TRAM flap for breast reconstructions. Br. J Plast Surg 1997, 50:322-330 22. Dancey A., Blondeel PN. Technical tips for safe perforator vessel dissection applicable to all perforator flaps. Clin Plast Surg 2010; 37: 593-606 23. Keys KA, Louie O, Said HK, Neligan PC, Mathes DW. Clinical utility of CT angiography in DIEP breast reconstruction. J Plast Reconstr Aesthetic Surg. 2013;66(3):61–5. 24. Itoh Y, Arai K. The deep inferior epigastric artery free skin flap: Aantomic study and clinical application. Plast Reconstr Surg. 1993,91 (5):853-63. discussion 864 25. Giunta RE, Geisweid A, Feller AM. The value of preoperative Doppler sonography for planning free perforator flaps. Plast Reconstr Surg. 2000;105(7):2381–6.

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Dynamic infrared thermography (DIRT) in DIEP flap breast reconstruction: standardization of the measurement set-up

This chapter has been published as: Filip Thiessen, Thierry Tondu, Nicolas Vermeersch, Ben Cloostermans, Ralv Lundahl, Bart Ribbens, Lawek Berzenji, Veronique Verhoeven, Guy Hubens, Gunther Steenackers, Wiebren Tjalma. Dynamic infrared thermography (DIRT) in DIEP flap breast reconstruction: standardization of the measurement set-up. Gland Surgery 2019;8(6):799-805 | http://dx.doi.org/10.21037/gs.2019.12.09. Chapter 4: Contents

Abstract 93 4.1. Introduction 94 4.2. Material and Methods 95 Cooling 95 Infrared camera 97 Tripod 97 Software and data transmission 99 4.3. Measurement strategy 99 Preoperative 99 Perioperative 99 Postoperative 101 4.4. Discussion 101 4.5. Conclusion 102 4.6. References 103 DIRT in DIEP flap breast reconstruction: standardization of the measurement set-up

Abstract

Breast reconstruction with an autologous free deep inferior epigastric perforator (DIEP) flap is one of the preferred options following mastectomy. A challenging step in this procedure is the selection of a suitable perforator that provides sufficient blood supply for the flap.

The current golden standard for perforator mapping is computed tomography angiography (CTA). However, this is a relatively expensive imaging modality that requires intravenous contrast injection and exposes patients to ionizing radiation. More recently, dynamic infrared thermography (DIRT) has been proposed as an alternative imaging modality for perforator identification. DIRT appears to be an ideal alternative technique not only for the identification of the dominant perforators, but also for the mapping of the individual influence of each perforator on the flap perfusion. Multiple studies have been performed with the use of DIRT, unfortunately without standardisation of the measurement set-up.

In this technical note we propose a standardised and reproducible measurement set- up for the use of DIRT during breast reconstructions with a free DIEP flap. This set-up can be used pre-, intra- and postoperatively. A standardised measurement set-up will improve the quality of measured data and ensure reproducibility.

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4.1. Introduction

reast reconstruction with a deep inferior epigastric artery perforator (DIEP) flap is a common option for reconstruction after mastectomy. In breast reconstructions with DIEP flaps, the skin and subcutaneous tissue from the patient’s lower abdomen are Bused as a free flap to reconstruct the breast. The flap receives its blood supply from the deep inferior epigastric artery and one or two concomitant veins through a perforator. Following dissection of the flap, the flap is anastomosed to the internal mammary artery and vein for an optimal blood supply [1-3]. One of the key elements in DIEP flap surgery is the selection of the best perforators. Optimal perforator selection reduces operation times, complication rates and ensures an overall better result. Current techniques to locate perforator vessels include handheld Doppler, colour Doppler ultrasound (CDU), magnetic resonance angiography (MRA), computer tomographic angiography (CTA), and dynamic infrared thermography (DIRT) [4, 5]. The current golden standard for perforator selection is CTA on which the location and hemodynamic properties of the flap can be assessed. CTA is frequently used because it is non-invasive and has a high spatial resolution with visualisation of the intramuscular course of the vessels. However, this technique has disadvantages, such as the use of intravenous (IV) contrast agents and ionizing radiation, high purchasing costs, a lack of perioperative usability, and a lack of physiological information on flow characteristics of perforators [4]. An alternative technique that has gained popularity in recent years is dynamic infrared thermography (DIRT). DIRT is less invasive than CTA because it does not use radiation nor contrast agents. It is based on measurements of heat emission by tissues and skin temperature with the use of infrared (IR)-cameras. Data obtained with DIRT can be used to generate color-coded maps that strongly correlate to the perfusion of the skin. DIRT is generally used as a dynamic investigation technique, meaning that the skin must undergo a thermal cold challenge. After this cold challenge, DIRT measures the rate and patterns of rewarming. With this method, clinicians are able to identify the most dominant perforators and their perfusion area [6, 7]. Earlier studies have shown that DIRT can be a valuable addition during all phases of breast reconstructions with DIEP flaps. DIRT is a quick imaging technique that is available pre-, peri-, and post-operatively [7-14]. DIRT is a valuable alternative to clinical examination to evaluate at any stage during surgery the perfusion of the flap [15]. DIRT can also be an interesting alter-

94 DIRT in DIEP flap breast reconstruction: standardization of the measurement set-up

native to the use of inodcyanine green to evaluate the microcirculation and perfusion of the flap peroperatively. DIRT is less invasive than the use of indocyanine green because there is no need for contrast agents. Moreover the potential allergic reactions to ICG should be taken into consideration [16]. Furthermore, DIRT is easy to interpret and has a low purchasing cost. On the other hand, DIRT only provides information on the physiology of the perforator and not on the morphology. This means that the surgeon must have a thorough knowledge of the vascular anatomy in order to interpret the results [6]. When applying DIRT in a clinical setting, there a lot of factors to take into account. The choice of cameras, software, and cooling methods are crucial for successful measurements. In medical literature the description of the measurement set-up for DIRT is very diverse [14]. Only a standardised and reproducible measurement set-up will improve the quality of the measured data and will make comparisons between subjects or studies possible. The goal of present technical note is to describe a new and standardized measurement method for the use of DIRT in the pre-, peri- and post-operative setting. The setup proposed in this study is based on a combination of several strategies found in earlier studies [7-11, 13, 17].

4.2. Material and Methods

Cooling

The introduction of a cold or heat challenge is recommended to create an even starting situation for the whole area of interest [7, 13, 18]. Locat- ing the perforators is easier with a cold challenge because the appearing hotspots are clearer against an even background. Cooling ensures that only the areas which are best supplied with blood will become noticeable hotspots in the minutes after removal of the excitation [19]. The reduction of the so called “fake hotspots” is critical for the accuracy of this method. Fake hotspots are small areas where superficial blood vessels give the impression of an underlying perforator. The implemented cooling method to achieve the introduction of the cold challenge is a sterile bag filled with water and ice. The water inside the bag has a temperature of 3 to 5°C. The bag is positioned on the abdomen for a certain cooling time. It has to cover the entire area of interest and follow the contour of the abdomen to ensure an even cooling of the area. Creases in the plastic bag can cause uneven cooling of the area of interest and may lead to false appearing hotspots after

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(a) Cooling with filled sterile bag. (b) Image after cooling with aluminium plate. Figure 4.1. Different cooling methods.

removal of the sterile bag (Figure 4.1). This technique is the result of a comparison between different cooling methods: First cooling with sterile compresses soaked in saline at 5 degrees was tested. This method was not ideal due to the interference of the water left behind on the surface at the beginning of the IR-measurement. The cooling was not even, nor was the amount of extracted heat from the abdomen sufficient. Secondly, an aluminium plate wrapped in a sterile drape was pressed against the abdomen [7]. This technique has been described, but was found unfit because of uneven cooling (Figure 4.1b). The thermal image showed warmer lines across the abdomen where the creases had been. This made the image distorted and therefore not comparable. Cooling with alcohol was tested [20]. Alcohol extracts heat from the skin to evaporate and cools the skin. The evaporation happened too quickly and drained too little heat. No even cooling was obtained due to unevenly dispersed alcohol on the abdomen and fast evaporation time.

The parameters to hold into account when optimizing the cooling method are the cooling capacity, the contact surface, and the cooling time. The

96 DIRT in DIEP flap breast reconstruction: standardization of the measurement set-up

equation below shows the relation between these parameters. Q= m . Cp. ∆T/t Where: Q = Cooling capacity (kW) m = mass (kg) Cp = specific heat capacity of cooling liquid (kJ/kgK) ∆T = temperature change (K) t = cooling time (s)

The equation shows an inverse relation between cooling time and temperature change. To obtain an optimal cooling time while preventing tissue damage due to low temperatures, a balance between these parameters needs to be found. In this set-up, a water temperature of 5 °C and a cooling time of 3 minutes are used to provide a sufficient cooling capacity without damaging tissues or creating a long cooling time.

Infrared camera

For the measurements, a thermal imaging camera is used. An uncooled, long wavelength microbolometer camera is used because of its compact size, high image resolution, and precision at relatively low temperature- measurements. In our setting we use the Xenics Gobi 640. The Gobi 640-series has a high sensitivity for small signals due to a low noise detector. A frame rate of 50 Hz is be used to see the emerging hotspots. We compared the quality of the images with the Xenics Gobi 640 to the FLIR X6800SC, with appropriate filters in order to match the wavelength range of the Xen- ics Gobi 640. The Flir IR camera has a quantum detector which means they have to be cooled to approximately -196°C. This makes this type of camera large and therefore less practical in an operating room, on top of that the quality of the results was similar. The long wave IR-cameras are less expensive compared to the medium wave cameras and are often used in technical and medical domains [21]. For the dynamic measurements, the data consist of video files of 5 minutes. The recording starts at the moment the cooling (or vascular clamp) is removed from the area of interest.

Tripod

The IR-camera is positioned above the patient. The optimal position for the IR-camera is perpendicular to the abdominal area. In this position the

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camera can capture the clearest view of the flap (Figure 4.2). The fixed position of the camera will allow automated image analysis. Furthermore, the exact distance of the camera with respect to the measured object can be inserted as input for the software in order to measure accurate distances on the thermal image. In order to obtain this perpendicular position above the abdomen of the patient, a tripod with an arm length of 250 cm including a counterweight is used. The tripod is mounted on wheels to enable manoeuvring. The tripod can be placed at the foot end of the operation table to prevent interference with the operating surgeon (Figure 4.3). The tripod is mounted on wheels to enable manoeuvring during surgery. To ensure every measure-

(a) Perpendicular position of the camera. (b) Camera at unknown angle. Figure 4.2. Camera positioned in different angles.

Figure 4.3.Position of the tripod and the camera in the operating room (not disturbing the surgeon during surgery).

98 DIRT in DIEP flap breast reconstruction: standardization of the measurement set-up

ment has the exact same camera position relative to the operation table or bed, markings are drawn on the tripod and the ground. In our set-up, the Manfrotto Black Light Boom 025B tripod is used.

Software and data transmission

Importing and editing camera data was performed using Xeneth v2.6.0 (Xenics, Leuven). This software shows the taken images in real-time and allows the operator to adjust the scaling. Raw data can also be imported into Matlab (MathWorks, Natick, MA) for further post processing. The power supply of the thermal imaging camera and the data transfer is realized over one Power over Ethernet (PoE) cable.

4.3. Measurement strategy

The standardized measurement strategy makes the technique reproducible and ensures that different test subjects are comparable. A breast reconstruction with a DIEP flap can be divided into a preoperative, perioperative, and postoperative section.

Preoperative

A static image is made of the abdomen without cooling, as a control image. Subsequently, the cold challenge is performed and recording of the measurements is started. The cold challenge induces the appearance of hotspots which identify the dominant perforators [9, 10].

Perioperative

The perioperative measurements are taken after dissection of the perforators [22, 23]. The first measurement is a recording after the cold challenge with all the dissected perforators open/unclamped. A comparison is made between the hotspots and the actual perforators to see whether they correlate (Figure 4.4). The goal of the second intraoperative measurement is to map the specific influence of each perforator on the perfusion of the flap. A microvascular clamp is used to clamp the perforator temporarily until the flap shows no heated areas. Subsequently, one of the clamps is removed and the recording is started. This provides a good visualization of the influence of the perforator on flap perfusion (Figure 4.5). This procedure is repeated according to the number of perforators that are dissected.

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(a) Cooled abdominal area (b) 4 minutes after removal of cold challenge. with the hotspots encircled. Hotspots encircled. Figure 4.4. Intraoperative measurement with cooling.

(a) Initial state (immediate (b) Steady state (4 minutes after clamp removal). after clamp removal). Figure 4.5. Intraoperative measurement with clamps.

Figure 4.6. Flap anastomosed in steady state. The red line marks the edge of area with good perfusion.

100 DIRT in DIEP flap breast reconstruction: standardization of the measurement set-up

The last measurement takes place after the flap is anastomosed. Record- ing starts immediately after opening the venous and arterial anastomosis. The flap undergoes a cold challenge due to the non-perfusion during flap ischemia. An extra cold challenge can be performed after the anastomosis when needed. The last measurement determines the influence of the anastomosis on the flap perfusion. These data can be used to identify, and discard, less vascularized parts of the flap (Figure 4.6).

Postoperative

In the postoperative period, DIRT can potentially detect early (partial) necrosis. After 1-2 postoperative days, 2 measurements will be taken: 1 static image of the reconstructed breast and 1 dynamic image after a cold challenge. The same measurement set-up as during surgery can be used on the ward.

4.4. Discussion

Dynamic thermography in breast reconstructions with DIEP flaps has shown to be a valuable addition in the pre-, peri- and postoperative period. DIRT is able to measure the rate and patterns of rewarming after cooling, which allows clinicians to identify the dominant perforators and the perfusion-area [6, 7, 14]. There is a great variety in measurement set-ups in literature which makes comparisons between the different techniques difficult. The introduction of the cold challenge is very variable in literature. De Weerd et al. introduce a cold challenge by blowing air over the abdomen for 2 minutes using a desktop fan. Afterwards, a recording is made with an IR camera for 3 minutes [6, 7, 10, 24, 25]. The difficulty with using a cold air stream is to obtain an even and homogenous cooling of the abdomen. Further- more, the cooling capacity of cold air is lower than that of cold water. This can potentially cause bigger hotspots and complicate pinpointing the exact location of perforators. In addition to this, cooling with a desktop fan is impossible in the operation room. Another technique is the use of a metal plate to introduce a cold challenge perioperatively [7]. This metal plate only allows cooling of a small area and does not follow the curve of the abdomen. Water-packs have been used to introduce a cold challenge [13]. In this study, a sterile bag with cold water is used because it can be shaped according to the contour of the abdomen and due to its ability to evenly

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cool the whole area of interest. Moreover, the use of the bag with water is possible during all moments of the surgical procedure. The choice for a 3-minute cooling period instead of 10 minutes cooling prevents potential tissue damage. A prolonged exposure of the abdomen to cold temperatures may cause damage to the subdermal plexus and diminish the visibility of hotspots [17, 19]. Positioning of the camera is very variable in literature. The optimal position for the IR-camera is perpendicular to the abdominal area. In this position the camera can capture the clearest view of the area of interest. By using a fixed position of the camera in the perpendicular position, the images will not be distorted and automated image analysis will be possible. In other set-ups the camera was a handheld version or the abdomen was framed under an angle [20].

4.5. Conclusion

Multiple studies show that DIRT is a valuable tool during breast reconstruction with free DIEP flaps: it is a safe, low-cost, and quick imaging tool that provides information on location of the perforators, blood flow, and functional characteristics of the vessels. The measurement set-up for DIEP flap DIRT measurements has a large impact on the results. In this study, a new measurement set-up is proposed that can be applied in the pre-, peri-, and postoperative period of the reconstruction and provides reproducible results. In the future, continuous thermography may be used to detect early venous or arterial problems. Al- though DIRT is a promising technique, larger studies are needed to provide more conclusive results.

102 DIRT in DIEP flap breast reconstruction: standardization of the measurement set-up

4.6. References

1. Blondeel PN. One hundred free DIEP flap breast reconstructions: a personal experience. Br J Plast Surg. 1999;52(2):104-11. 2. Thiessen FEF, Tjalma WAA, Tondu T. Breast reconstruction after breast conservation therapy for breast cancer. Eur J Obstet Gynecol Reprod Biol. 2018;230:233-8. 3. Tondu T, Tjalma WAA, Thiessen FEF. Breast reconstruction after mastectomy. Eur J Obstet Gy- necol Reprod Biol. 2018;230:228-32. 4. Mohan AT, Saint-Cyr M. Advances in imaging technologies for planning breast reconstruction. Gland Surg. 2016;5(2):242-54. 5. Nahabedian MY. Overview of perforator imaging and flap perfusion technologies. Clin Plast Surg. 2011;38(2):165-74. 6. de Weerd L, Mercer JB, Weum S. Dynamic infrared thermography. Clin Plast Surg. 2011;38(2):277-92. 7. de Weerd L, Mercer JB, Setsa LB. Intraoperative dynamic infrared thermography and free-flap surgery. Ann Plast Surg. 2006;57(3):279-84. 8. de Weerd L, Miland AO, Mercer JB. Perfusion dynamics of free DIEP and SIEA flaps during the first postoperative week monitored with dynamic infrared thermography. Ann Plast Surg. 2009;62(1):42-7. 9. de Weerd L, Weum S, Mercer JB. The value of dynamic infrared thermography (DIRT) in perfora- torselection and planning of free DIEP flaps. Ann Plast Surg. 2009;63(3):274-9. 10. Weum S, Mercer JB, de Weerd L. Evaluation of dynamic infrared thermography as an alternative to CT angiography for perforator mapping in breast reconstruction: a clinical study. BMC Med Imaging. 2016;16(1):43. 11. Tenorio X, Mahajan AL, Elias B, van Riempst JS, Wettstein R, Harder Y, et al. Locating perforator vessels by dynamic infrared imaging and flow Doppler with no thermal cold challenge. Ann Plast Surg. 2011;67(2):143-6. 12. Weum S, Lott A, de Weerd L. Detection of Perforators Using Smartphone Thermal Imaging. Plast Reconstr Surg. 2016;138(5):938e-40e. 13. Whitaker IS, Lie KH, Rozen WM, Chubb D, Ashton MW. Dynamic infrared thermography for the preoperative planning of microsurgical breast reconstruction: a comparison with CTA. J Plast Reconstr Aesthet Surg. 2012;65(1):130-2. 14. John HE, Niumsawatt V, Rozen WM, Whitaker IS. Clinical applications of dynamic infrared thermography in plastic surgery: a systematic review. Gland Surg. 2016;5(2):122-32. 15. Thiessen FEF, Tondu T, Cloostermans B, Dirkx YAL, Auman D, Cox S, et al. Dynamic InfraRed Thermography (DIRT) in DIEP-flap breast reconstruction: A review of the literature. Eur J Obstet Gynecol Reprod Biol. 2019;242:47-55. 16. Li K, Zhang Z, Nicoli F, D'Ambrosia C, Xi W, Lazzeri D, et al. Application of Indocyanine Green in Flap Surgery: A Systematic Review. J Reconstr Microsurg. 2018;34(2):77-86.

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17. de Weerd L, Weum S, Mercer JB. Dynamic Infrared Thermography (DIRT) in the preoperative, intraoperative and postoperative phase of DIEP flap surgery. J Plast Reconstr Aesthet Surg. 2012;65(5):694-5; author reply 5-6. 18. Kolacz S, Moderhak M, Jankau J. New perspective on the in vivo use of cold stress dynamic thermography in integumental reconstruction with the use of skin-muscle flaps. J Surg Res. 2017;212:68-76. 19. Zetterman E, Salmi A, Suominen S, Karonen A, Asko-Seljavaara S. Effect of cooling and warming on thermographic imaging of the perforating vessels of the abdomen. European journal of plastic surgery. 1999;22(2-3):58-61. 20. Walle L, Fansa H, Frerichs O. [Smartphone-based thermography for perforator localisation in microvascular breast reconstruction]. Handchir Mikrochir Plast Chir. 2018;50(2):111-7. 21. Vollmer M, Möllmann K-P. Infrared thermal imaging : fundamentals, research and applications. Weinheim: Wiley-VCH; 2010. xvii, 593 p. p. 22. Kalra S, Dancey A, Waters R. Intraoperative selection of dominant perforator vessel in DIEP free flaps based on perfusion strength using digital infrared thermography - a pilot study. J Plast Reconstr Aesthet Surg. 2007;60(12):1365-8. 23. Lohman RF, Ozturk CN, Ozturk C, Jayaprakash V, Djohan R. An Analysis of Current Techniques Used for Intraoperative Flap Evaluation. Ann Plast Surg. 2015;75(6):679-85. 24. de Weerd L, Weum S, Mercer JB. Detection of perforators using thermal imaging. Plast Reconstr Surg. 2014;134(5):850e-1e. 25. de Weerd L, Weum S, Mercer JB. Locating perforator vessels by dynamic infrared imaging and flow Doppler with no thermal cold challenge. Ann Plast Surg. 2014;72(2):261.

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Dynamic infrared thermography (DIRT): clinical studies

Chapter 5 Part A

DIEP flap breast reconstructions: thermographic assistance as a possibility for perforator mapping and improvement of DIEP flap quality

This chapter has been published as: Jan Verstockt*, Filip Thiessen*, Ben Cloostermans, Wiebren Tjalma, and Gunther Steenackers. DIEP Flap Breast Reconstructions: Thermographic Assistance as a Possibility for Perforator Mapping and Improvement of DIEP Flap Quality. *Equally contributing first authors. Applied Optics Vol. 59, No. 13 / 1 May 2020 / https://doi.org/10.1364/AO.388351 Chapter 5A: Contents

5.1. Introduction 109 Current methods 110 5.2. Dynamic infrared thermography (DIRT) 111 5.3. Emissivity of human skin 112 5.4. Experimental conditions 113 5.5. Instrumentation 114 Infrared thermal camera 115 Display device and image processing unit 116 Transient measurement equipment 116 5.6. Measurements on DIEP flaps: method 117 Preoperative measurements: external cooling 118 Peroperative measurements 120 Postoperative measurements 120 Post-processing 120 5.7. Results and discussion 122 Preoperative measurements 122 Peroperative measurements 122 Peroperative measurements with hemostatic clamps 122 Peroperative measurements after anastomosis to the mammary artery and veins 123

5.8. Conclusion 124 The need for post-processing 125 5.9. References 126 DIEP flap breast reconstructions: thermographic assistance

n the modern world still one-third or more of breast cancer patients undergo uni- or bilateral mastec-tomy. Breast cancer patients, in general, have a good prognosis and long-term survival. Therefore, the treatment must not only focus on survival but also on the quality of Ilife. Breast reconstruction with an autologous free DIEP (Deep Inferior Epi- gastric artery Perforator) flap is one of the preferred options after mastectomy. A challenging step in this procedure is the selection of a suitable perforator that provides sufficient blood supply for the flap to prevent necrosis after anastomosis. In this pilot study, the possibilities for dynamic infrared thermography (DIRT) are investigated to select the best suitable perforator. The measurements are done with external cooling in the preoperative stage to accurately predict the location of the dominant perforators. During the surgery, in the peroperative stage, measurements are done for mapping the influence of a specific perforator on the perfused areas of the abdominal flap. Perforators are sequentially closed and opened again to map the influence of that perforator on the vascularization of the flap, visualized with the help of the thermographic camera. The acquired steady- state thermal images could help decide which parts of the abdominal flap to use for the reconstruction so that the chance on (partial) necrosis is reduced. In the postoperative stage, DIRT could visualize the arterial and or venous thrombosis before they become clinical obvious as (partial) necrosis. At present DIRT seems to be a valu-able investigation for the pre-, per- and postoperative phases of DIEP-flap reconstructions. Large high quality clinical studies are needed to determine its definitive role.

5.1. Introduction

Belgium has the highest incidence of breast cancer in women per capita (113.2/100,000) which totals to around 11,000 women each year according to Thiessen et al. [1]. One third (34%) of the breast cancer patients undergo uni- or bilateral mastectomy and 1 out of 7 undergo reconstruction surgery. Half of which are performed with autologous tissue. Thirtyt- wo percent of the autologous tissue flaps are deep inferior artery epigastric perforator (DIEP)-flaps [1–3]. A DIEP flap breast reconstruction is thus commonly used for breast reconstruction after mastectomy. A DIEP flap is a perforator flap that only transplants skin and subcutaneous tissue. The breast is reconstructed without sacrificing any of the abdominal muscles. In exceptional cases, the transplanted tissue lacks sufficient blood supply. This results in cell injury, cell death and tissue necrosis [4]. The healing pro-

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cess can lead to extra surgical procedures with added physical and mental distress. The current state-of-the-art is the use of Computed Tomography Angiography (CTA) and Doppler Imaging to locate the perforators and reveal the hemodynamic properties of the flap [5]. These current selection techniques have weaknesses like invasiveness, use of ionizing radiation and intravenous contrast medium or are imprecise. Dynamic Infrared Ther- mography (DIRT) can be an added-value by tackling those weaknesses by being non-invasive, quick, inexpensive to use and accurate. Studies [6] so far indicate that IRT can be successfully used for diagnosis of breast cancer, diabetes, dentistry, diabetic neuropathy, etc. In the coming years, the use of IRT in the medical field is likely to surge. Here we discuss the results and techniques used in this pilot study during preoperative and peroperative stage and the possible use in postoperative stage.

Current methods

There are multiple methods to locate perforating vessels in the flap, such as CT angiography, Doppler ultrasound and ICG fluorescence angiography (ICG-FA). According to Kolacz et al. an ideal method in a clinical setting meets the following conditions: non-invasiveness, simplicity, repeatability, the ability of peroperative assessment, and low cost [7]. Dynamic infrared thermography (DIRT) is a non-invasive monitoring technique, unlike ICG-FA and CT-A and is used in clinical medicine as a mechanism to measure skin temperatures [8]. A review with the advantages and disadvantages of (MD) CTA, Doppler/CDU, MRA and DIRT is done by Thiessen et al. [1] CT-A is currently the gold standard for perforator mapping in breast reconstructions with DIEP flaps. Although, it can cause complications because it requires ionizing radiation and the use of intravenous contrast medium [9, 10]. It is also known for being time consuming and expensive. The hemodynamic properties can also be registered by a Doppler echo. This technique is completely painless and uses ultrasonic sound waves. Cifuentes et al. mentions that strong Doppler correlates with larger hot spots in DIRT [11]. Additionally, stronger Doppler signals have also been suggested to be correlated with larger perforator vessels [11]. DIRT uses the principle of thermal radiation. Every object emits natural infrared radiation which can be registered by a thermal camera. This technique does not use damaging radiation nor additional medium. According to the preliminary data of the DIRT method in comparison with other state- of-the-art methods (CRA, (MD)CTA, Handheld Doppler/CDU) as mentioned in the review paper by Thiessen et al. [1], DIRT is, therefore, a promising

110 DIEP flap breast reconstructions: thermographic assistance

technique for being the least invasive but accurate method for determining the hemodynamic properties [1]. Most results with the application of DIRT for DIEP flap monitoring are reported in the publications of de Weerd et al. [10, 12]. Recently the first standardised set-up for DIRT and DIEP flap reconstruction was published [13].

5.2. Dynamic infrared thermography (DIRT)

Perforators that transport blood to the subdermal plexus cause local heating at the skin surface [10]. When performing a cold challenge, the perforators can be located with the help of a thermographic camera. Dur- ing the rewarming process, the perforators become visible as the skin surface starts to warm up again. This technique can be used preoperative, peroperative and postoperative. To visualize the perforators, a cold challenge must be performed. The temperature changes of the skin must be in a physiological range to prevent permanent tissue damage [14]. The period of rewarming starts as soon as the cold challenge stops. At this point, there are no hot spots visible. After some time, the first hot spots become visible. These hot spots represent the perforators. The thermal images are analysed to find the hot spots and to discover the pace and pattern of the rewarming. The first occurring hot spots can be related to perforators with a larger blood supply. A fast rewarming indicates a perforator which trans- ports more blood to the skin surface. Progressive reheating around the hot spot illustrates a well-developed vascular network around this location. [10]. As a result of analyzing the images, the surgeon can obtain information about the hemodynamic properties of the blood vessels in the flap. This can be crucial to select the perforator that vascularizes the flap. This potentially diminishes the occurrence of partial necrosis of the flap due to poor vascularization. An optional postoperative test can be performed to analyse the blood supply and ensure a successful surgery. The method of static thermography does not render an unequivocal indication of the location of the perforators [7]. Several studies of dynamic thermography [7, 9] are available which include different methods for ob- taining a temperature difference to reveal the dynamic properties. The flap was stimulated with high and low temperatures. The number of hot spots was smaller when a heat stimulation was used in contrast to cold stimulation [7]. The area was cooled down 5-6 C or heated up by 5-6 C to avoid damage by burning the tissue [7]. A small stimulation amplitude produces a poorer signal in relation to measurement noise. This shows the need for

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post-processing in order to enhance the IR images. In our case, a cold challenge was used to reveal the dynamic properties. The hot spots and perforators were clearly visible on the IR-images but post-processing can make them potentially even more visible. Dynamic thermography is a useful tool to reduce the time of perforator selection and can be performed at any stage of surgical treatment.

5.3. Emissivity of human skin

Body surface temperature can be measured with the use of an IR camera. The outcome of a complicated combination of central and local regula- tory systems is reflected by the surface temperature of an extremity. As a living organism, the human body tries to maintain homeostasis, that is, an equilibrium of all systems within the body, for all physiological processes, which leads to dynamic changes in heat emission [15]. The dynamic changes in heat emission depend on internal (eg. blood flow, hormones, smoking, exercise, emotion, etc.) and external (eg. room temperature, humidity, clothing, cosmetics, etc.) conditions. This makes it inevitable to develop standard procedures during surgery in order to be able to interpret thermal imaging results. The most important factor seems to be arterial blood flow as surface temperature increases with intensified blood flow [16]. According to Vollmer [15], emissivity e is a measure of the efficiency in which a surface emits thermal energy. It is defined as the ratio of thermal energy (radiation) from a surface being emitted relative to that emitted by a thermally black surface (a black body) at the same temperature. A black body is a material that is a perfect emitter of heat energy and has an emissivity value of 1. A material with an emissivity value of 0 would be considered a perfect thermal mirror. As reported by Lee and Minkina, the generally accepted emissivity e of human skin, independent of the skin colour, is 0.98 0.01 which makes the human skin a nearly perfect black body [17, 18]. Hardy and Muschenheim concluded that dead skin can be regarded as a perfectly black surface with an emissivity of e = 1 [19]. The average skin surface temperature is 32 C [18]. In our case, a cold challenge is performed. This reveals the dynamic properties of the flap. It is therefore not necessary to determine the absolute temperature. Although it is still important to keep the errors constant during the measurement. For standardization, the following five major conditions, given by Cockburn, should be fulfilled in order to avoid common errors [20].

112 DIEP flap breast reconstructions: thermographic assistance

>Proper room conditions • Minimum size of 9 m2 • Constant room temperature (23.5 C) • Humidity of 45-60% • Avoid turbulent airflow close to the patient (heat emitters, ventilators, air conditioning) • Reduce effect of sunlight with shades • Proper selection of material on walls and ceiling >Proper preparation of the patient • Acclimatization for at least 15 min, taking off clothes from areas to be examined • No intake of food, alcohol, coffee, tea 2 h before examination • No physical exercise 24 h before examination • No excessive tanning or sun burns 7-10 days before examination >Standardized equipment • Calibrated IR camera, low NETD (Noise Equivalent Temperature Differ- ence) • Camera switched on at least 1 h before examination in the same room (thermal shock) >Proper recording and storage of acquired images • Avoid grazing incidence of radiation on camera, select viewing angle close to 0° since # = #(angle) • Include gender, age diagnosis, current medication, size, weight, room conditions, and date >Representation of images • Standardized temperature scale, often a span 23-36 or 24-38 C.

5.4. Experimental conditions

Experimental conditions like the temperature of the surroundings (Table 5.1), moisture as well as airflow have an influence on the infrared radiation emitted by a surface. Controlled environments are thus an absolute neces- sity for thermographic experiments. It is even more important in medical applications where the temperature differences are only a few degrees. Standardization or a standard protocol is key to make it possible to compare thermographic images. This standardization should comply with five major conditions to avoid common errors, as mentioned before. The standardized measurement setup to obtain the results in this article is described by Thiessen et al. [13]

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Table 5.1. Experimental conditions used by various research groups for recording of infrared thermal images [6]. Ambient room Acclimation Researchers [Ref.] Year Study temperature ( C) time (min) Bagavathiappan et al. 2010 Diabetic neuropathy 25 5 [21] Bouzida et al. [22] 2009 Thermoregulation 24 2 10

Park et al. [23] 2007 Shoulder impingement syndrome 19-21 15 Sun et al. [24] 2006 Diabetic at-risk feet 21 1 15-20

Hosaki et al. [25] 2002 Peripheral circulation in subjects 20 15 with diabetes mellitus Gratt et al. [26] 1998 Facial telethermography 21-23 15 Armstrong et al. [27] 1997 High risk diabetic foot 21 2 15

Branemark et al. [28] 1967 Diabetes mellitus subjects 18-20 15-50

In order to perform a primary investigation with respect to the usage of IR-thermography during surgery, the researchers attended a breast reconstruction by means of a DIEP flap. During the reconstructions, the researchers performed thermal measurements on the patient that can act as a foundation for more dedicated measurements during a follow-up measurement campaign. A unilateral breast reconstruction using the DIEP flap technique means that both the left or right sides of the lower abdominal wall can be chosen for transplantation. A bilateral breast reconstruction using the DIEP flap technique means that both the left and the right flap are used to reconstruct both breasts. Infrared thermography can possibly facilitate the choice regarding perforator selection.

5.5. Instrumentation

Infrared thermography experiments require a set of professional instrumentation [6] which consists of an infrared thermal camera, a long-arm tripod (Figure 5.1), a display device, and an image processing unit. A transient measurement is obtained by stimulating the tissue. The measurement set- up for DIRT is standardized by Thiessen et al. [13] and is used in all the measurements. It is important that measurements can be performed during any time of the surgery without disturbing the surgeon.

114 DIEP flap breast reconstructions: thermographic assistance

Infrared thermal camera

The most recent generation cameras have a large focal plane array (FPA) detectors and on-chip image processing. Thermal cameras are categorized into two types: cooled and uncooled. Currently, the thermal sensitivity of the uncooled camera is about 0.05 C in comparison to 0.01 C of the cooled ones which will provide better detail. The cooled cameras have a very fast capture rate, have greater magnification capabilities than uncooled cameras due to sensing shorter infrared wavelengths and are able to easily perform spectral filtering. However, the uncooled cameras have some advantages which are useful for this application of perforator mapping such as compactness, portability, light-weighted, less maintenance and inexpensive compared to cooled cameras. Although the cooled infrared thermal cameras have a greater thermal sensitivity, the uncooled IR thermal cameras have a high enough thermal sensitivity and spatial resolution which makes them usable for this application. There have been reported great results by using a smartphone-based thermal camera [11]. It is important for the post-processing procedure to select a thermal camera with the features for storing both thermal and visual images [29]. Cameras used by other research-groups for medical applications are tabulated in Table 5.2.

(a) Measurement setup with long-arm tripod [13]. (b) Cooling method with sterile plastic bag filled with ice and water [13].

Figure 5.1. Measurement setup to perform IR-thermography measurements on DIEP- flap.

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Table 5.2. IR cameras used for different studies by various research groups for medical thermography experiments. Researchers [Ref.] Year Study Camera used Bagavathiappan et al. 2010, Diabetic neuropathy and vascular AGEMA Thermovision 550, Nikon [21, 30] 2009 disorder Laird S270 (Tokyo, Japan) Perforator Selection and Planning FLIR ThermaCAM S65 HS (FLIR de Weerd et al. [31] 2009 of Free DIEP Flaps Systems) Bouzida et al. [22] 2009 Thermoregulation FLIR Phoenix Model Park et al. [23] 2007 Shoulder impingement syndrome IRIS 5000 (Medicore, Seoul, Korea) AGEMA Thermovision 470 and Brioschi et al. [32] 2007 3D MRI and IR image fusion ThermaCAM P65HS (FLIR Systems) Spectrum 9000 MB; Bio vision tech- Sun et al. [24] 2006 Diabetic at-risk feet nologies, Inc. Taipei, Taiwan Effect of induced evaporation on HR-II Medical Infrared Imaging Deng and Liu [33] 2005 thermal diagnostics of tumors System, IOE of North China Peripheral circulation in subjects Infrared ray thermo tracer 6T66 Hosaki et al. [25] 2002 with diabetes mellitus (NEC-Sanei Co. Japan) Lo [34] 2002 Acupuncture Meditherm 2000 Shevelev [35] 1998 Functional imaging of brain AGA Thermovision 780 M Exergen DT 1001 infrared skin tem- Armstrong et al. [27] 1997 High risk diabetic foot perature probe Clinical and experimental derma- Carlo [36] 1995 tology Aga Thermovision 680 Thermoregulation and effect of psychological factors on skin Aga Thermovision 780 & 880; Infra- Gulyaev et al. [37] 1995 temperature com-93 & TV-03 (Russia) Microwave heating enhanced Thompson et al. [38] 1978 thermal detection of tumors Aga Thermovision 1680

Display device and image processing unit

Display and image processing are done digitally using a computer or lap- top and dedicated software packages. A connection between the thermal camera and the computer enables the possibility for real-time measurements and post-processing. This results in a reduction of surgery time.

Transient measurement equipment

In order to perform a transient measurement, equipment for stimulating the tissue is necessary. The meaning of stimulation is to create a temperature difference between the blood supply and the tissue. There are several studies [7, 9–11, 29, 31, 39–41] available which include cold and heat stimulation. The most common techniques are listed: • Blowing air at room temperature (desktop fan) [10, 11, 31].

116 DIEP flap breast reconstructions: thermographic assistance

• Blowing cooled air with the use of a cooling unit [7]. • Applying cold water packs[13]. • Applying an alcohol-based solution in combination with blowing air [41]. • Halogen lamps [7]. • Using hemostatic clamps to block blood flow (peroperative) [13].

Some of these techniques are not tolerated during surgery because they are non-sterile, which results in additional risks for the patient. The high need for standardisation of stimulation methods for transient measurements has been countered by Thiessen et al. [13].

5.6. Measurements on DIEP flaps: method

The camera used for the thermal images is a Xenics Gobi 640 microbolometer 640x480, NETD 30mK, 50Hz with 7.5-14 μm spectral range. This is an uncooled, long-wavelength microbolometer camera and is chosen because of its compact size, high image resolution, and precision at relatively low temperature-measurements [13]. The performed measurements during breast reconstruction with the used thermal camera delivers an image sequence (3D-matrix) shot at ca 6.25Hz [42]. A frame rate of 6.25 Hz is used to clearly visualize the emerging hot spots. The format of the data set is a three-dimensional matrix [m n o] with m pixels width, n pixels height and o frames. The measuring unit is C. No absolute temperatures are measured,

Figure 5.2. Postoperative image of the reconstructed breast one day after surgery. The IR-camera can visualize potential necrosis.

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only temperature differences are displayed so calibration of the thermal camera is not necessary. The measurements are divided into 3 sections: pre-, intra- and postoperative. Each section of a measurement has a different purpose, as shown in the list below [43]. • Preoperative : Pinpoint the exact location of the dominant perforators. • Peroperative : Mapping the specific influence of each perforator on the abdominal flap regarding blood supply. As well as defining the perfused area of the flap after transplantation. Monitoring of perfusion after anastomosis and flap inset. • Postoperative : Examining whether or not thermal images can give an early warning to avoid partial or complete necrosis (thrombosis).

Preoperative measurements: external cooling

The purpose of the preoperative measurement is to accurately determine the location of the dominant perforators. Therefore, an ideal thermal image for this section would be one with few but obvious hot spots. The reduction of the so-called ’fake hot spots’ is critical for the accuracy of this method. ’Fake hot spots’ are small areas where superficial blood vessels give the impression of an underlying perforator [13]. To obtain this ideal image, cooling was applied to make the hot spots narrower and to reduce the so-called ’fake hot spots’ [44]. Further research has to be done to reduce the number of ’fake hot spots’. The following criteria are involved when determining the most suitable perforators: • Perforator has a well-developed branching pattern right after passing through the abdominal muscles and the fascia [45]. This usually ensures that the perforator perfuses enough tissue of the abdominal flap. • The diameter of the perforator must be large enough. This ensures a sufficient flow of blood to perfuse a large enough area of the abdominal flap. • The way the perforator passes through the rectus abdominis muscle determines the dissection time. The surgeons tend to choose perforators which lie near the medial line and close to the umbilicus [46].

In Figure 5.3 the most explicit hot spots are encircled in red. The locations where the perforators pass through the fascia according to the CTA images are represented. The actual CTA images are slices right above and parallel to the fascia (anterior rectus sheath). The black circle on the drawings represents the umbilicus. On the actual CTA images, the umbilicus is

118 DIEP flap breast reconstructions: thermographic assistance

represented by a white circle. The umbilicus makes linking of the images possible. During the measurements, the abdomen is cooled with a sterile plastic bag filled with ice and water (Figure 5.1(b)) [13]. By comparing the locations of the hot spots, right after cooling, with the locations of the perforators as seen on the CTA, we can investigate the accuracy of the method used. The surgeon marked the best-suited perforators (according to his judgement) with a cross on the schematic drawings (Figure 5.3(e)). The blue crosses are the perforators which were clamped off in the peroperative measurements [43].

(a) Right after cooling was removed. (b). After 4 minutes of rewarming.

(c). Location of the potentially suitable (d). Visualization of the quick and strong bran- perforators seen on the CTA. ching pattern of perforator B.

Figure 5.3. Preoperative measurement. The cooling was done in a plastic bag filled with ice and water. This bag was drapped and slightly pressed.

(e). Schematic representation of the perforator.

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Peroperative measurements

The peroperative measurements for mapping the influence of a specific perforator will determine which areas of the abdominal flap will be perfused by which dominant perforator (e.g. Figure 5.5). This information can influence the choice of considered perforators. This, of course, in a situation where there are multiple perforators. The best-suited perforators can appear to have similar properties on the CTA, yet their heated areas of the abdominal flap will have a different surface area. The perforator that perfuses the largest part of the abdominal flap is most likely to be chosen for transplantation. Currently, the choice of what area of the abdominal flap is used for transplantation is a clinical evaluation based on the CTA images and the experience of the surgeon. As described by Hembd et al. up to 14,4 percent had flap fat necrosis [47, 48]. Thus there is room for optimization in determining which part of the flap is well perfused through the selected perforator and which part of the flap is safe to use. The surgeons do not exactly and with certainty know the maximum surface area perfused by the chosen perforators when examining the CTA images [43]. Before transplantation, the best-suited perforator which perfuses most likely the largest part of the abdominal flap is chosen to be anastomosed. After anastomosis, the blood flow in the DIEP flap can be checked with DIRT to verify if the flap is properly vascularized to reduce the chance of necrosis.

Postoperative measurements

One to two days after the surgery a static image of the reconstructed breast and a dynamic recording after the introduction of a cold challenge are taken as can be seen in Figure 5.2. With those two measurements there is a possibility that the IR-camera can visualize potential necrotic area(s), due to arterial or venous thrombosis, before clinical observation [49]. Fur- ther research has to be done in the postoperative phase and is not further discussed in this article.

Post-processing

The peroperative measurements take place during several phases of the surgery. The surgeon needs instant feedback on the measurements of the DIEP flaps without obstructing the time window of the surgery. No real- time post-processing for determining hot spots and perforators has been

120 DIEP flap breast reconstructions: thermographic assistance

(a) Measurement at time zero. (b) Measurement at 8 minutes.

Figure 5.4. Thermal measurements with left flap in rest and perforator A open.

(a). Perforator A and B ca. 4 minutes af- (b). Only perforator B ca. 4 minutes ter the clamp was removed. after the clamp was removed. Figure 5.5. Peroperative measurement. The influence of perforator A on the flap can be deduced by subtracting the influence of perforator B in (a). Perforator B was eventually chosen for transplantation because its heated and subsequently perfused area is much larger than the heated c.q. perfused area of perforator A.

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tested yet as discussed further in this article. The realtime acquired image sequence is visualized with the "Xeneth64" software delivered by the manufacturer of the IR-camera Xenics Gobi 640 microbolometer 640x480. The chosen color profile is "16-bit grayscale", the temperature scale as well as the range to histogram thresholds has been adjusted to fit the measured temperatures and data.

5.7. Results and discussion

Preoperative measurements

Perforators A1 and A2 in Figure 5.3 originate from the same pedicle and could potentially be used together when sacrificing the muscle. Perforators A1 and A2 emerge both from the deep inferior epigastric artery and vein. They can be used together to vascularize the DIEP flap but means that the surgeon has to sacrifice a part of the muscle. The 2 perforators (A1 and A2) can be correlated with 2 hot spots in Figure 5.3. Namely, the upper hot spot just above the umbilicus and the lowest hot spot. Perforator B swiftly splits into 2 branches and curves sharply to the anatomical left side as seen in Figure 5.3. This matches with the thermal image after 4 minutes of rewarming, Figure 5.3. Eventually, perforator B was chosen for its well- developed branching pattern and therefore its large perfused area.

Peroperative measurements

Peroperative measurements with hemostatic clamps After dissection of the DIEP flap with the perforators still connected, blood flow can be controlled in the different parts of the flap by closing and opening perforators with the help of hemostatic clamps. In Figure 5.4 the region vascularized by A is clearly noticeable. At time stamp zero, perforator A is opened and the evolution is tracked for 5 minutes. It can be noticed that the bottom part of the flap cools down, the top and middle part of the flap is vascularized by perforator A and the temperature increased and stabilized. In a different case, Figure 5.5, when the clamps on perforator A and B are removed and steady-state conditions are achieved after 4 minutes, it can be seen that both perforators together vascularize the flap well. When perforator B is opened while keeping perforator A closed, one can notice the region that is perfused by perforator B. The effect of opening a perfo-

122 DIEP flap breast reconstructions: thermographic assistance

rator can clearly be visualized by looking at the thermal measurement at different moments in time.

Peroperative measurements after anastomosis to the mammary artery and veins As illustrated in the steady-state images in Figure 5.6, it becomes possible to distinguish the colder from the warmer areas on the abdominal flap. The warmer areas indicate blood perfusion and thus a minimal chance of necrosis after transplantation. It now becomes possible to paste red lines onto the steady-state images which will mark the separation line between

(a) Peroperative measurement 1: perforator B was con- (b) Peroperative measurement 2: only the small upper nected to the chest artery. This image depicts the flap right part of the considered flap does not seem to warm as steady state 5 min after blood flow was reintroduced up in the 5 min after clamp removal. Therefore, this part and indicates the maximal surface area of the flap that of the flap has the most chance of developing partial could safely be used for reconstruction. necrosis.

(c) Peroperative measurement 3: the blue line in this image repre- (d) Peroperative measurement 4: the war- sents where the surgeon made the cut. After the dynamic analysis mer/whiter areas outside of the red lines do of the sequence of thermal images, the red line was drawn onto not have a temperature change throughout the division between the parts that reheated and the parts that the 5 min measuring time. This implies that did not. The upper enclosed area defines the area that was cut off, these areas have been warmed by external even though it was perfused. The lower enclosed area represents factors, e.g., conduction of body heat, the a preserved section that will have a chance of necrosis. surgeon’s hands, etc. Figure 5.6. Perfused area of DIEP flap after anastomosis of the DIEP flap has been completed. The red line displays sufficient and insufficient perfused areas in the DIEP flap.

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the warmer and the colder areas caused by the chosen connected perforator. However, defining the well-perfused area has to be done by analysing the reheating process over the ca. 5 minutes following the clamp removal after the anastomosis has been completed. This will ensure that the visualised temperature difference on the thermal images is solely produced by the reintroduction of warm blood. Only a steady-state image will be able to indicate the different surface areas. This is because of the conduc- tive heating of the flap by perfusion. These thermal images could help the surgeon to decide which parts of the abdominal flap to use for the actual reconstruction of the breast.

5.8. Conclusion

From the presented initial results in this pilot study based on a small amount of patient samples, one can conclude that infrared thermography offers extra information on the location of the perforators and its vascularization pattern. In the future, DIRT can be a promising alternative to CTA for preoperative perforator mapping in DIEP flap breast reconstruction. In this pilot study, the enhanced preoperative measurement results are obtained using our standardized measurement setup [13] are in accordance with the published results by De Weerd et al. [31]. However, in this initial study, particular emphasis is placed on peroperative measurements with our improved and standardized measurement setup during surgery. The measurements are interesting and deliver promising results to assist the surgeon. A large clinical study is needed in order to reveal how far one can go with infrared thermography for identifying perforators in an accurate manner. Also, during surgery, IR thermography can identify which zone of the free flap is to be used for the reconstruction, depending on the level of bleed through the flap. The correlation between the best-suited perforators and hot spots should be determined as well as the correlation between the hot spots on the thermal images and the perforator locations seen on the CTA images. Additionally, Infrared Thermography clearly visualizes the perforators which have the largest perfusion area. A large supply of blood is only one of the main criteria used when determining the best-suitable perforators for transplantation. Perforators which have an extremely well-developed branching pattern may be invisible right after the cooling is removed, however, they will start to re-appear in the moments following the removal of the cold challenge.

124 DIEP flap breast reconstructions: thermographic assistance

The applied techniques can be used to determine the location of the dominant perforators. A prominent hot spot does not always equal to a dominant perforator. Furthermore, it is impossible to pinpoint the exact location of where the perforator passes through the fascia. This is due to the anatomy of the perforators and the fact that thermal cameras only measure the superficial temperatures. There is an inseparable link between the depth of the perforator and its visibility on thermal images because these measurements are superficial. The deeper parts of the perforator, when the perforator doesn’t go straight up, will have to warm up more abdominal tissue before they become visible on the thermal images.

The need for post-processing

It becomes obvious that the heat development of the hot spots over a certain time is a determining factor. As well as the expansion rate of the warmed-up surface area with the hot spot as the source. Therefore, the image right after the removal of cooling does not represent the entire result of the test. In most cases, a static comparison between the images, taken a certain time apart, will not be sufficient to determine the most dominant perforator(s). Consequently, a need for dynamic analysis of the series of images arises. Through post-processing, the visualization of the data can be optimized and compressed. This allows easy analysis and use of the measured thermal images by non-experts in the field of thermography. The mapping of the influence of the different dominant perforators over a set time (5 minutes) has proven to be a useful tool. The thermal images provide the individual influence of each perforator on the flap, as well as the dimensions of the perfused area. This additional information is an asset when determining the best-suited perforator(s) for transplantation. The visual separation between the warmer, perfused area and the colder area can visualize the sections that will possibly develop necrosis just by analysing a 5-minute measurement. This easy, non-invasive technique can minimise the chances of partial necrosis. In conclusion, the non-invasive thermal measurements provide the surgeon with real-time visualization of the considered perforators and their influence on the flap.This additional information can definitely optimize the choices made regarding the selection of the best-suitable perforator and the determination of the maximal perfused area of the flap.

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5.9. References

1. F. E. F. Thiessen, T. Tondu, B. Cloostermans, Y. A. L. Dirkx, D. Auman, S. Cox, V. Verhoeven, G. Hubens, G. Steenackers, and W. A. A. Tjalma, “Dynamic InfraRed Thermography (DIRT) in DIEP- flap breast reconstruction: A review of the literature,” Eur. J. Obstet. & Gynecol. Reproductive Biol. 242, 47–55 (2019). 2. WHO - International Agency Research for Cancer, “Cancer WHO-iafro. Estimated age-standardized incidence rates (World) in 2018,all cancers, both sexes, all ages [Internet],” http://gco.iarc. fr/today/online-analysis-map?projection=globe (2018). Accessed: 2020-03-26. 3. KCE, “KCE. Borstreconstructie na kanker in drie cijfers [Internet].” https://kce.fgov.be/nl/news/ borstreconstructie-na-kanker-in-drie-cijfers (2019). Accessed: 2020-03-26. 4. S. S. Kroll, “Necrosis of Abdominoplasty and Other Secondary Flaps after TRAM Flap Breast Reconstruction,” Plast. reconstructive surgery (1994). 5. R. Ohkuma, R. Mohan, P. A. Baltodano, M. J. Lacayo, J. M. Broyles, E. B. Schneider, M. Yamazaki, D. S. Cooney, M. A. Manahan, and G. D. Rosson, “Abdominally based free flap planning in breast reconstruction with computed tomographic angiography,” Plast. Reconstr. Surg. 133, 483–494 (2014). 6. B. B. Lahiri, S. Bagavathiappan, T. Jayakumar, and J. Philip, “Medical applications of infrared thermography: a review,” Infrared Phys. Technol. 55, 221–235 (2012). 7. S. Kołacz, M. Moderhak, and J. Jankau, “Comparison of perforator location in dynamic and static thermographic imaging with Doppler ultrasound in breast reconstruction surgery,” Quant. Infrared Thermogr. pp. 407–410 (2016). 8. Å. O. Miland, L. de Weerd, and J. B. Mercer, “Intraoperative use of dynamic infrared thermography and indocyanine green fluorescence video angiography to predict partial skin flap loss,” Eur. J. Plast. Surg. 30, 269–276 (2007). 9. E. Swanson, A. Street, and U. States, “Dynamic infrared thermography for the preoperative planning of microsurgical breast reconstruction : A comparison with CTA,” Elsevier. pp. 130–132 (2011). 10. S. Weum, J. B. Mercer, and L. de Weerd, “Evaluation of dynamic infrared thermography as an alternative to CT angiography for perforator mapping in breast reconstruction: A clinical study,” BMC Med. Imaging 16 (2016). 11. I. J. Cifuentes, B. L. Dagnino, M. C. Salisbury, M. E. Perez, C. Ortega, and D. Maldonado, “Aug- mented reality and dynamic infrared thermography for perforator mapping in the anterolateral thigh,” Arch. Plast. Surg. 45, 284–288 (2018). 12. L. de Weerd, J. B. Mercer, and S. Weum, “Dynamic infrared thermography,” Clin. Plast. Surg. 38, 277–292 (2011). 13. F. E. F. Thiessen, T. Tondu, N. Vermeersch, B. Cloostermans, R. Lundahl, B. Ribbens, L. Berzenji, V. Verhoeven, G. Hubens, G. Steenackers, and W. A. A. Tjalma, “Dynamic infrared thermography (DIRT) in Deep Inferior Epigastric Perforator (DIEP) flap breast reconstruction: standardization of the measurement set-up,” Gland Surg. 8 (2019).

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14. S. P. Fagan, J. Goverman, P. E. Parsons, and J. P. Wiener-Kronish, “Chapter 66 - Burns and Frost- bite,” in Critical Care Secrets (Fifth Edition), (Mosby, Philadelphia, 2013), pp. 461–467. 15. M. Vollmer and K.-P. Mollmann, Infrared thermal imaging: fundamentals, research and applications (Wiley-VCH, 2018), 2nd ed. 16. M. Vollmer and K.-P. Möllmann, “Medical applications,” in Infrared Thermal Imaging: Fun- damentals, Research and Applications, (Wiley-VCH, Weinheim, 2013), chap. Medical Ap, pp. 535–546. 17. Y. Y. Lee, M. F. Md Din, Z. Z. Noor, K. Iwao, S. Mat Taib, L. Singh, N. H. Abd Khalid, N. Anting, and E. Aminudin, “Surrogate human sensor for human skin surface temperature measurement in evaluating the impacts of thermal behaviour at outdoor environment,” Meas. J. Int. Meas. Confed. 118, 61–72 (2018). 18. W. Minkina and S. Dudzik, Infrared Thermography - Errors and Uncertainties (John Wiley & Sons, 2009). 19. J. D. Hardy and C. Muschenheim, “The radiation of heat from the human body. IV The emission, reflection and transmission of infrared radiation by the human skin,” The journal clinical investigation pp. 817–831 (1934). 20. W. Cockburn, “Common errors in medical thermal imaging,” in Common errors in medical thermal imaging, (Wiley-VCH, 2006), 7, pp. 165–177. 21. S. Bagavathiappan, J. Philip, T. Jayakumar, and B. Raj, “Correlation between plantar foot temperature and diabetic neuropathy by using an infrared thermal imaging technique,” J. Diabetes Sci. Technol. 4, 1386–1392 (2010). 22. N. Bouzida, A. Bendada, and X. P. Maldague, “Visualization of body thermoregulation by infrared imaging,” J. Therm. Biol. 34, 120–126 (2009). 23. J. Park, J. K. Hyun, and J. Seo, “The effectiveness of digital infrared thermographic imaging in patients with shoulder impingement syndrome,” J. Should. Elb. Surg. 16, 548–554 (2007). 24. P. Sun, H. Lin, S. E. Jao, Y. Ku, R. Chan, and C. Cheng, “Relationship of skin temperature to sym- pathetic dysfunction in diabetic at-risk feet,” Diabetes Res. Clin. Pract. 73, 41–46 (2006). 25. Y. Hosaki, F. Mitsunobu, K. Ashida, H. Tsugeno, M. Okamoto, N. Nishida, S. Takata, T. Yokoi, Y. Tanizaki, K. Ochi, and T. Tsuji, “Non-invasive study for peripheral circulation in patients with diabetes mellitus,” Annu. reports Misasa Med. Branch 72, 31–37 (2002). 26. B. Gratt and M. Anbar, “Thermology and facial telethermography: Part II. Current and future clinical applications in dentistry,” Dentomaxillofacial Radiol. 27, 68–74 (1998). 27. D. G. Armstrong, L. A. Lavery, P. J. Liswood, W. F. Todd, and J. A. Tredwell, “Infrared dermal ther- mometry for the high-risk diabetic foot,” Phys. Ther. 77, 169–175 (1997). 28. P. Branemark, S. Fagerberg, L. Langer, and J. S. Soderbergh, “Infrared thermography in diabetes mellitus,” Diabetologia. 3, 529–532 (1967). 29. L. Rees, M. Moses, and J. Clibbon, “The anterolateral thigh (ALT) flap in reconstruction following radical excision of groin and vulval hidradenitis suppurativa,” J. Plast. Reconstr. Aesthetic Surg. 60, 1363–1365 (2007).

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30. S. Bagavathiappan, T. Saravanan, J. Philip, T. Jayakumar, B. Raj, R. Karunanithi, T. Panicker, M. P. Korath, and K. Jagadeesan, “Infrared thermal imaging for detection of peripheral vascular disorders,” J. Med. Phys. 34, 43–47 (2009). 31. L. de Weerd, S. Weum, and J. B. Mercer, “The Value of Dynamic Infrared Thermography DIRT in Perforator Selection and Planning of Free DIEP Flaps,” Annals Plast. Surg. 63, 274–279 (2009). 32. M. L. Brioschi, I. Sanches, and F. Traple, “3D MRI/IR imaging fusion: a new medically useful computer tool,” in Inframation Proceedings, Las Vegas, (2007). 33. Z. S. Deng and J. Liu, “Enhancement of thermal diagnostics on tumors underneath the skin by induced evaporation,” in 27th Annual Conference of IEEE Engineering in Medicine and Biology, Sanghai, China, (2005). 34. S.-y. Lo, “Meridians in acupuncture and infrared imaging,” Med. Hypotheses 58, 72–76 (2002). 35. I. A. Shevelev, “Functional imaging of the brain by infrared radiation (Thermoencephaloscopy),” Prog. Neurobiol. 56, 269–305 (1998). 36. A. D. Carlo, “Thermography and the possibilities for its applications in clinical and experimental dermatology,” Clin. Dermatol. 13, 329–336 (1995). 37. Y. V. Gulyaev, A. G. Markov, L. G. Koreneva, and P. V. Zakharav, “Dynamical infrared thermography in humans,” IEEE Eng. Medicine Biol. Mag. 14, 766–771 (1995). 38. J. E. Thompson, T. L. Simpson, and J. B. Caulfield, “Thermographic tumor detection enhancement using microwave heating,” IEEE Transactions on Microw. Theory Tech. 26 (1978). 39. Å. O. Miland, L. De Weerd, S. Weum, and J. B. Mercer, “Visualising skin perfusion in isolated human abdominal skin flaps using dynamic infrared thermography and indocyanine green fluorescence video angiography,” Eur. J. Plast. Surg. 31, 235–242 (2008). 40. D. Chubb, W. M. Rozen, I. S. Whitaker, and M. W. Ashton, “Images in plastic surgery: Digital thermographic photography ("Thermal Imaging") for preoperative perforator mapping,” Annals Plast. Surg. 66, 324–325 (2011). 41. M. V. Muntean, S. Strilciuc, F. Ardelean, and A. V. Georgescu, “Dynamic infrared mapping of cutaneous perforators,” J. Xiangya Medicine 3, 16–16 (2018). 42. G. Steenackers, J. Peeters, P. M. Parizel, and W. Tjalma, “Application of passive infrared thermography for DIEP flap breast reconstruction,” in QIRT 2018 Proceedings Page, (QIRT, 2018), pp. 25–29. 43. Steenackers, Verstockt, Cloostermans, Thiessen, Ribbens, and Tjalma, “Infrared Thermography for DIEP Flap Breast Reconstruction Part I: Measurements,” Proceedings 27, 48 (2019). 44. G. Steenackers, B. Cloostermans, F. Thiessen, Y. Dirkx, J. Verstockt, B. Ribbens, and W. Tjalma, “Infrared Thermography for DIEP Flap Breast Reconstruction Part II: Analysis of the Results,” Proceedings 27, 49 (2019). 45. S. Weum, J. B. Mercer, and L. de Weerd, “The value of Dynamic Infrared Thermography (DIRT) in perforator selection and planning of free DIEP flaps,” Annals Plast. Surg. 63, 274–279 (2009). 46. H. H. El-Mrakby and H. Milner R., “The vascular anatomy of the lower anterior abdominal wall: a microdissection study on the deep inferior epigastric vessels and the perforator branches.” Plast. Reconstr. Surg. (2000).

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47. S. M. D. Bonomi, L. M. D. Sala, and U. M. D. Cortinovis, “Optimizing Perforator Selection: A Mul- tivariable Analysis of Predictors for Fat Necrosis and Abdominal Morbidity in DIEP Flap Breast Reconstruction,” Plast. Reconstr. Surg. 143, 887–888 (2019). 48. A. Hembd, S. S. Teotia, H. Zhu, and N. T. Haddock, “Optimizing Perforator Selection: A Multi- variable Analysis of Predictors for Fat Necrosis and Abdominal Morbidity in DIEP Flap Breast Reconstruction,” Plast. Reconstr. Surg. 142 (2018). 49. D. Brooks, J. Prince, B. Parrett, B. Safa, R. Buntic, and G. Buncke, “Post-operative Perfusion Monitoring with the Near Infrared SPY System,” in 6th Congress of the World Society for Reconstructive Microsurgery (WSRM), E. Tukiainen, ed., World Soc Reconstruct Microsurgery (Medimond S.r.l., Bologna, 2011), pp. 163–166. ISBN 978-887-587-612-8.

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Chapter 5 Part B

Dynamic infrared thermography (DIRT) in DIEP flap breast reconstruction: a clinical study with a standardized measurement setup

This chapter has been published as: Thiessen FEF, Vermeersch N, Tondu T, Van Thielen J, Vrints I, Berzenji L, Verhoeven V, Hubens G, Verstockt J, Steenackers G, Tjalma WAA. Dynamic Infrared Thermography (DIRT) in DIEP flap breast reconstruction: A clinical study with a standardized measurement setup. Eur J Obstet Gynecol Reprod Biol. 2020 Sep;252:166-173. doi: 10.1016/j.ejogrb.2020.05.038. Chapter 5B: Contents

Abstract 133 5.10. Introduction 134 5.11. Material and methods 135 Measurement strategy 136 Preoperative 136 Intra-operative 136 Postoperative 136 Measurement setup 137 5.12. Results 138 5.13. Discussion 140 Preoperative 140 Intraoperative phase 141 Post-operative phase 144 5.14. Conclusion 144 5.15. References 146 Dynamic infrared thermography (DIRT) in DIEP flap breast reconstruction

Abstract

Objective: Breast reconstructions with perforator flaps from the lower abdomen, commonly known as Deep Inferior Epigastric artery Perforator flap (DIEP-flap), have become the golden standard for autologous breast reconstruction after breast amputation. During this surgical procedure multiple challenging steps are encountered such as the selection of a suitable perforator that provides sufficient blood supply for the flap, surgical dissection of the chosen perforator, determination of perfusion area of the chosen perforator, microsurgical anastomosis, flap inset and shaping the flap into a breast. The current gold standard for perforator mapping is Computed Tomography Angiography (CTA). However, this is a relatively expensive imaging modality that requires intravenous contrast injection and exposes patients to ionizing radiation. More recently, Dynamic Infrared Thermography (DIRT) has been proposed as an alternative imaging modality for perforator identification. DIRT appears to be an ideal alternative technique not only for the identification of the dominant perforators, but also for the mapping of the individual influence of each perforator on the flap perfusion, to monitor integrity of the perforator after dissection and to monitor the patency of the pedicle of the free flap after the anastomosis, during flap inset and flap shaping.

Study Design: In this clinical study we present the results of the use of DIRT in 33 DIEP- flaps in 21 patients after mastectomy. The same standardized measurement set-up was used for all the flaps in the pre-, intra- and postoperative period.

Results: In the pre-operative period DIRT confirmed the location of the 69 perforators shown on the CTA. In the intra-operative period the rate and pattern of rewarming was successfully observed. One perforator was severely damaged during dissection and the DIEP flap was converted to a Muscle Sparing free Transverse Rectus Abdominis Muscle (TRAM) flap, after viability check of the flap by DIRT. DIRT diagnosed one kinking of the pedicle after microsurgical anastomosis. Two flaps were monitored successfully post-operatively. All 33 breast reconstructions were with good outcome.

Conclusion: The use of DIRT with our standardized measurement setup is a useful, non-invasive tool during breast reconstructions with free DIEP-flaps in all the phases of the reconstruction (pre-, intra- and post-operative). This study confirms that DIRT with the standardized measurement setup provides information on perforator location, blood supply and patency of the anastomosis without interference with the operating surgeon.

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5.10. Introduction

reast cancer is the most common cancer in women with more than two million new cases in 2018 [1]. The treatment often involves a mastectomy. Reconstruction following mastectomy offers women an opportunity to mollify some of the emotional and Baesthetic effects of this disease. Autologous breast-reconstruction remains the technique associated with the highest patient satisfaction and represents the preferred technique for recreation of the breast [2, 3]. Recon- structions with Deep Inferior Epigastric-artery Perforator-flaps (DIEP-flap) have become the gold standard for autologous breast-reconstruction. The abdominal donor site remains unmatched due to its volume, color and texture resemblance with native breast tissue [4, 5]. The skin and subcutaneous tissue from the lower abdomen are transplanted to the thorax to reconstruct the breast. The flap is perfused from the deep inferior epigastric vessels through a perforator. The blood supply to the flap is re-established by anastomosing the pedicle of the flap to the internal mammary vessels. The selected perforator is the only source of blood supply to the flap. Selection of the best perforators is of uttermost importance in this procedure. This will reduce operative time, lower complication rates and ensure an overall better result. There are multiple methods of locating perforators: Computed Tomography Angiography (CTA), Doppler ultrasound (CDU), Magnetic Resonance Angiography (MRA) or Dynamic Infrared Ther- mography (DIRT)[6, 7]. The current gold standard is CTA on which the location and hemodynamic properties of the perforators can be reviewed. CTA is non-invasive and has a high spatial resolution with visualisation of the intramuscular course of the vessels. However, this technique has a number of disadvantages: the use of intravenous contrast, exposure to radiation, high costs, lack of perioperative use and the lack of physiological data on flow characteristics [6, 8]. In order to be considered ideal in clinical conditions, a method should meet the following conditions: non-invasive, simple, repeatable, intra-operative assessment and low cost. DIRT can be an alternative. DIRT uses an infrared-camera to measure the skin temperature based on heat emitted by tissues. This generates a color-coded map, which is a translation for the skin perfusion. DIRT is a dynamic investigation technique; meaning that the skin must undergo a thermal cold challenge. The DIRT measures the rate and patterns of rewarming after cooling. This technique allows to identify the dominant perforators and the area they perfuse [9-13].

134 Dynamic infrared thermography (DIRT) in DIEP flap breast reconstruction

DIRT is less invasive than CTA due to its lack of use of radiation or contrast agents. Furthermore, it is a quick imaging technique that is easily interpretable by the surgeon, has a low purchasing cost and is available pre-, intra- and post-operatively. However, DIRT only provides data on the physiology of the perforator and not on the morphology. This means that the surgeon must have a thorough knowledge of the anatomy to interpret the results. Not only the selection of the perforators is mandatory for successful breast-reconstructions with free-flaps. Flap failure in breast-reconstructions is often due to technical failures during the dissection of the perforator, failure of the anastomosis or due to kinking or compression of the pedicle during flap-inset and shaping. These technical errors occur regardless of the experience of the surgeon. Earlier studies have shown that intra-operative monitoring of free flaps is crucial to prevent flap failure [10, 14-17]. Clinical monitoring of free-flaps is based on skin-color, skin-turgor, dermal edge bleeding and capillary-refill. These methods are user dependent and experience related. In the intra- and postoperative settings, infrared-thermography can be a valuable monitoring tool [10, 18]. Despite its advantages regarding free-flap monitoring, there is a lack of data regarding the optimal choice of cameras, cooling methods and measurement setup [19]. In a previous paper, we described a standardized setup that is applicable during all phases of breast-reconstructions without the need for alteration of the setup and without disturbing the surgeon [20]. The aim of this paper is to describe the use of DIRT during the pre-, intra- and postoperative period of DIEP-flap breast-reconstructions with this standardized measurement setup.

5.11. Material and methods

This prospective clinical study was carried out to evaluate the use of DIRT with one standardized setup during all phases of DIEP-flap breast- reconstructions. Prior to surgery all patients underwent a CTA to determine the location and intramuscular course of the perforators. This preoperative CTA is carried out routinely since 2010 [21]. All IR-thermal images were taken after acclimatization to operation room (OR)-temperature. These measurements are performed in the OR on the day of surgery to prevent extra hospital admissions. During the pre-, intra- and postoperative period the standardized measurement setup is used

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[20]. The data are assessed immediately by the surgeon. No additional processing of the images is performed.

Measurement strategy

Preoperative The perforators detected on the CTA are marked on the abdomen. Meanwhile a static image of the abdomen is made without cooling, as a control image. Subsequently, the cold challenge is performed and the measurements are started. The cold challenge induces the appearance of hotspots in order to identify the dominant perforators [11, 20, 22].

Intra-operative The intra-operative measurements take place after dissection of the perforators. The first measurement is a recording after cold challenge with all the dissected perforators open/unclamped. This allows a comparison between the hotspots and the actual location of the perforators in order to see whether they correlate. The goal of the intra-operative measurement is to check if the perforators were not damaged during dissection and to record the reheating-pattern. Microvascular clamps are used to clamp the perforators until the flap shows no heated areas. Subsequently, one of the clamps is removed and the recording is started. This provides a good visualization of the influence of each perforator on flap perfusion. The next measurement takes place after opening the microvascular anastomosis of the flap. The flap undergoes a cold challenge due to the non-perfusion during flap ischemia. The pattern of reheating is compared to the pattern on the abdomen. The final measurement is performed after flap-inset to assess patency of the pedicle after flap-shaping.

Postoperative In the postoperative period, DIRT can potentially detect early (partial) necrosis. After 1-2 days postoperatively, 2 measurements will be performed: 1 static image of the reconstructed breast and 1 dynamic image after a cold challenge. The same measurement setup is used.

136 Dynamic infrared thermography (DIRT) in DIEP flap breast reconstruction

Measurement setup

The measurement setup and cooling used in this study was comprehen- sively described by our research group [20]. (Figure 5.7 and 8, Table 5.3)

Table 5.3. Overview of measurement strategy

Preoperative Peroperative Postoperative

•Staticimageas •DIRTtoassess •Staticimage as reference potentialdamageto reference •DIRTtolocate perforators •DIRTtoassess perfortors • Sequentialclamping perfusion perforatorstoassess perfusionofeach perforator • Assessmentofpatency ofanastomosis •DIRTafterinsetofflap toassess perfusion

Figure 5.7. Cooling with sterile bag Figure 5.8. Position of infrared camera on tripod and infrared camera on tripod. The above the patient. The position does not disturb position of the infrared camera does the operating surgeon not disturb the operating surgeon.

137 Chapter 5B

5.12. Results

Thirty-three DIEP-flaps were performed in 21 patients with mean age of 56.7 years (range 33.9-71.6 years) and a mean BMI of 27.3 kg/m2 (range 21.3-32.9 kg/m2). Nine patients underwent a unilateral-reconstruction and 12 patients a bilateral-reconstruction. Fourteen were immediate breast- reconstructions, 11 were secondary and 8 were tertiary reconstructions (after other reconstruction). These data are shown in Table 5.4. Table 5.5 shows data on each individual patient. In the pre-operative phase, we were able to visualize 69 hotspots which correlated with 69 perforators on CTA. Intra-operatively, after dissection of the perforator, a cold challenge was performed to check the patency of the dissected perforators. A total of 45 perforators were successfully dissected. The location of the perforator clinically matched with the location of the hotspot. In patients with multiple suitable perforators, the perforator with the best progressive rewarming was selected. In one patient unfortunately the perforator was damaged during dissection. A DIRT-scan was performed to assess the viability of the flap and revealed the flap was still viable due the remaining attachment to the rectus fascia and muscle. The flap was converted to a Muscle Sparing-TRAM

Table 5.4. Patient characteristics Study population Patients (n=21) / DIEP Flaps (n=33) Patient characteristics Age: median (min-max) 55.3 (33.9-71.6) Body mass index (kg/m2): median (min-max) 27.3 (21.3-32.9) Diabetes mellitus 1 (4.7%) Hypercholesterolemia 3 (14.2%) Smoking 0 Arterial hypertension 4 (19%) Breast cancer treatment Chemotherapy 12 (57%) Radiotherapy 12 (57%) Hormone therapy 17 (80%) Reconstructive Surgery Unilateral reconstruction 9 (9 flaps) Bilateral reconstruction 12 (24 flaps) Immediate reconstruction 14 flaps Delayed Secondary 11 flaps Tertiary after expander reconstruction 5 flaps Tertiary after failed prosthesis reconstruction 3 flaps

138 Dynamic infrared thermography (DIRT) in DIEP flap breast reconstruction

(MS-TRAM)-flap. DIRT was also performed after anastomosis of the pedicle to the internal mammary vessels. A rapid and progressive rewarming was found in 32 flaps. In one patient no rewarming of the flap occurred due to kinking and spasm of the pedicle. After correction of the kinking, the flap recuperated. DIRT showed a rapid and progressive rewarming after shaping of the flap in all patients. No compression of the pedicle was noticed in our study- population. In the post-operative period one patient underwent a infrared-thermography of her reconstructed breasts. The measurement showed a successful perfusion of both flaps.

Table 5.5. Treatment-related data per patient. Pat. Recon- BMI Age Flap # Perfo- After dis- Perfora- Aanasto- Shaping Ward struction Side rator section tor Fl mosis 1 Unilat 25.5 64.4 contra 3 2 1 R/P R/P 2 Bilat 31.6 58.9 contra 3 1 1 R/P R/P contra 3 2 2 R/P R/P 3 Unilat 28.3 49.8 ipsi 5 3 2 R/P R/P 4 Bilat 31.2 52.9 contra 2 1 2 R/P R/P R/P contra 3 1 1 R/P R/P R/P 5 Unilat 28.4 66.9 contra 4 2 1 R/P R/P 6 Bilat 32.9 33.9 contra 2 1 1 R/P R/P contra 1 1 1 R/P R/P 7 Bilat 24.8 60.8 contra 1 1 1 R/P R/P contra 1 1 1 R/P R/P 8 Bilat 23.7 60.8 contra 1 1 1 R/P R/P contra 1 1 1 R/P R/P 9 Bilat 25.4 40.6 contra 2 2 2 R/P R/P contra 1 1 1 R/P R/P 10 Bilat 24.7 71.6 contra 1 1 1 R/P R/P contra 1 1 1 R/P R/P 11 Unilat 32.5 58.5 contra 3 2 2 R/P R/P 12 Unilat 25.1 46.4 contra 2 2 1 R/P R/P 13 Unilat 24.6 60.1 ipsi 4 2 2 R/P R/P 14 Bilat 22.7 55.1 contra 3 1 1 R/P R/P contra 2 2 2 R/P R/P 15 Bilat 29.6 53.2 contra 1 1 1 R/P R/P contra 1 1 1 R/P R/P 16 Bilat 30.5 59.8 contra 1 1 1 R/P R/P contra 2 TRAM TRAM R/P R/P 17 Unilat 21.3 60.6 contra 2 2 1 R/P R/P 18 Bilat 35.3 44.3 contra 1 1 1 R/P R/P contra 1 1 1 NO FLOW R/P 19 Unilat 21.8 53.5 contra 4 2 1 R/P R/P 20 Unilat 23.2 63.5 ipsi 5 2 1 R/P R/P 21 Bilat 29.8 37.1 contra 1 1 1 R/P R/P contra 1 1 1 R/P R/P Pat: Patient. Unilat: Unilateral Reconstruction Bilat: Bilateral Reconstruction BMI: Body Mass Index. Contra: Contralateral DIEP flap. Ipsi: Ipsilateral DIEP flap. #: number of. R/P: Rapid and Progressive rewarming

139 Chapter 5B

5.13. Discussion

In the last years, thermography has gained in popularity due to considerable improvements of the sensitivity of infrared-cameras. DIRT uses a thermal challenge to rule out interference from vascular patterns in the human body and measures the rate and pattern of rewarming after this challenge. With DIRT, colour-coded maps are created that visualize the vascular perfusion of the skin. In most cases, a rainbow palette is used for infrared-thermography [9]. Despite its popularity these colored maps have not shown to be superior to the grayscale map due to the fact that the human visual system is more sensitive to changes in luminance [23]. Itoh and Arai were the first to use DIRT to locate perforators [24]. Later studies have shown that DIRT is a valuable tool pre-, intra- and postoperatively for evaluation of perforators during breast-reconstructions with DIEP-flaps [9, 11, 22, 25]. In these studies multiple methods of cooling and installation of infrared-cameras were proposed. However, until now, no study was performed with the same measurement set-up during all phases of breast-reconstructions. The measurement setup described earlier by our group can be used during all phases of the reconstruction and does not interfere with the operating surgeon as the camera is mounted on a tripod which is positioned at the foot-end of the operation-table [20].(Figure 5.8)

Preoperative

Preoperative selection of the perforator is mandatory in order to reduce operative time, lower complication rates and ensure an overall better result [21, 26]. CTA is the current gold standard for perforator mapping. It provides an anatomical description on the caliber, location and intramuscular course of each perforator [27]. Some authors warn to solely rely on CTA-perforator-mapping, as they had to make multiple changes intraopera- tively in perforator selection [28]. CTA provides no physiological information of the perforators and leads to false-positive results when not compared to other imaging methods. This can be due to the fact that the size of a vessel on CTA is the sum of the diameters of the perforating artery and vein [29]. Other disadvantages of CTA are the exposure to ionizing radiation, high costs and the use of contrast. DIRT can provide additional information on the localization and quality of the perforators detected on the CTA [11, 22, 30]. DIRT not only evaluates the location of the perforator but also the rate of rewarming and the progression of the hotspot. Rapid rewarming of the hotspot shows a perforator that is capable to transport

140 Dynamic infrared thermography (DIRT) in DIEP flap breast reconstruction

more warm blood to the surface. A hotspot with rapid progression suggests a better vascular network. In our study all the perforators that where marked on the abdomen, are confirmed by a hotspot during DIRT. In 2 patients with very small perforators (<1 mm) on CTA, DIRT revealed a hotspot with good rewarming and good progression of the hotspot. During dissection the perforator revealed to be usable and the reconstruction could be performed successfully. To perform these measurements efficiently, the setup is done before the surgery starts.(Figure 5.7 and 8) The first measurement is performed after induction of the patient, during further installation of the patient by the anesthesiologist. This prevents the patient of an extra visit to the hospital and prevents prolongation of the surgical procedure. Our study confirms that DIRT is capable to confirm the location of perforators of DIEP-flaps preoperatively [11, 22, 30]. Moreover, by the use of DIRT extra information on the quality of the perforators is obtained. By combining DIRT and CTA-examinations one can have best of both worlds.

Intraoperative phase

Intraoperative monitoring of a DIEP-flap is mandatory to prevent flap failure [17]. Intraoperative evaluation of flap viability is routinely assessed by evaluating skin turgor, color, capillary refill and dermal edge bleeding. These methods are subjective and have a learning curve. More objective techniques as indocyanine-green-angiography (ICG) have been proposed. Although ICG-angiography provides an objective assessment of the perfusion, the costs are high and the repeated injection with the fluorescent dye gives a potential risk of allergic reactions [31]. We have used DIRT as an alternative intraoperative method for objective monitoring of flap perfusion with the same standardized measurement setup [10]. The cost of a reliable IR-camera is less than €20.000. The first DIRT measurement is performed after dissection of the chosen perforators. Cooling is necessary because the flap is continuously perfused by the perforator. In all patients, rapid rewarming at the location of the perforators was seen (Figure 5.9). In flaps where multiple perforators were dissected the impact of each perforator on the perfusion is evaluated by alternate clamping of the perforators. Subsequently, the perforator with the largest perfusion area is selected. The dissection of the DIEP-flap requires microsurgical skills and damage during surgery is inevitable. During dissection of one flap the pre-operatively chosen perforator was severely damaged. Immediate infrared-thermography was performed and showed

141 Chapter 5B

Figure 5.9a. Flap after dissection of perfo- b. After 60 sec rewarming, perforator shows rator and cold challenge (color palette and up (color palette and grayscale). The zone of grayscale). There is no rewarming visible. rewarming is shown with circle.

c: After 240 sec rewarming (color palette and grayscale). The area of rewarming becomes larger (circle).

142 Dynamic infrared thermography (DIRT) in DIEP flap breast reconstruction

rewarming of the flap through other, still intact perforators. The decision was made to harvest a free MS-TRAM. No flap-related complications and an excellent surgical result were seen postoperatively. The location of the initially visualised hotspots matched the location of the perforators after dissection in all patients except for one in which a TRAM-flap was used (the perforators were not visualized). The next challenging step is the anastomosis between the pedicle and the internal mammary vessels. We successfully used DIRT for intraoperative monitoring of reperfusion with the same measurement setup. The non-perfused flap during the microvascular anastomosis cools down which means that a thermal challenge is not necessary. In 32 flaps, rapid rewarming of the flap was seen after opening the anastomosis. This rewarming pattern was similar to the pattern seen on the abdomen.(Figure 5.10) In one patient no rapid rewarming was monitored due to vasospasm and kinking of the pedicle. The absence of rewarming was noticed instantly after opening the anastomosis, before clinical signs were present. Immediately after correction of the kinking a dramatic improvement of rewarming was seen. (Figure 5.11) This technique allows for an early detection of vascularization. No early venous or arterial thrombosis were seen in these 33 flaps.

Figure 5.10. Before microsurgical anastomosis: flap is cold due to ischemia (top of image, circle around flap); after microvascular anastomosis: rapid and progressive rewarming: circle around zone of rewarming (bottom of image).

143 Chapter 5B

The final DIRT measurement is performed after flap-inset and shaping. During shaping the pedicle can potentially be compressed or kinked. DIRT detects vascularization problems before they become clinically obvious. In all our patients a fast and overall rewarming was seen.(Figure 5.12)

Post-operative phase

In 2 flaps we performed measurements on the ward. These flaps showed rapid and overall rewarming after cold challenge. These preliminary results show that DIRT can be a valuable tool in the postoperative monitoring of DIEP-flaps, although a larger study is needed to confirm this.

5.14. Conclusion

This feasibility study shows that DIRT is a promising technique for selecting perforators and monitoring flap perfusion, used during all phases of breast reconstructions with one standardized measurement setup. When the camera is installed according to our standardized measurement setup, the operating surgeon is able to treat the patient without interference of the IR-camera. Further randomized controlled trials should be performed to assess the clinical outcome and cost-effectiveness of breast reconstructions with DIEP-flaps using DIRT.

144 Dynamic infrared thermography (DIRT) in DIEP flap breast reconstruction

a c

b d

Figure 5.11a. Flap before microvascular anastomosis, no rewarming (arrow). b. Flap 300 sec after opening microvascular anastomosis, no rewarming visible on color palette (arrow). c. Same picture as Figure 5.5.2 grayscale instead of color palette: no rewarming visible (arrow). d. Image immediate after correction kinking: rapid rewarming (oval)..

Figure 5.12. Cold challenge to bilateral DIEP in skin sparing mastectomy (top), Rapid and overall rewarming of the skin islands of the DIEP flap (bottom). Circle around skin islands of DIEP flap.

145 Chapter 5B

5.15. References

1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424. 2. Macadam SA, Bovill ES, Buchel EW, Lennox PA. Evidence-Based Medicine: Autologous Breast Reconstruction. Plast Reconstr Surg. 2017;139:204e-29e. 3. Serletti JM, Fosnot J, Nelson JA, Disa JJ, Bucky LP. Breast reconstruction after breast cancer. Plast Reconstr Surg. 2011;127:124e-35e. 4. Blondeel PN. One hundred free DIEP flap breast reconstructions: a personal experience. Br J Plast Surg. 1999;52:104-11. 5. Healy C, Allen RJ, Sr. The evolution of perforator flap breast reconstruction: twenty years after the first DIEP flap. J Reconstr Microsurg. 2014;30:121-5. 6. Mohan AT, Saint-Cyr M. Advances in imaging technologies for planning breast reconstruction. Gland Surg. 2016;5:242-54. 7. Nahabedian MY. Overview of perforator imaging and flap perfusion technologies. Clin Plast Surg. 2011;38:165-74. 8. Rozen WM, Garcia-Tutor E, Alonso-Burgos A, Acosta R, Stillaert F, Zubieta JL, et al. Planning and optimising DIEP flaps with virtual surgery: the Navarra experience. J Plast Reconstr Aesthet Surg. 2010;63:289-97. 9. de Weerd L, Mercer JB, Weum S. Dynamic infrared thermography. Clin Plast Surg. 2011;38:277- 92. 10. de Weerd L, Mercer JB, Setsa LB. Intraoperative dynamic infrared thermography and free-flap surgery. Ann Plast Surg. 2006;57:279-84. 11. de Weerd L, Weum S, Mercer JB. The value of dynamic infrared thermography (DIRT) in perfora- torselection and planning of free DIEP flaps. Ann Plast Surg. 2009;63:274-9. 12. Thiessen FEF, Tondu T, Cloostermans B, Dirkx YAL, Auman D, Cox S, et al. Dynamic InfraRed Thermography (DIRT) in DIEP-flap breast reconstruction: A review of the literature. Eur J Obstet Gynecol Reprod Biol. 2019;242:47-55. 13. Hennessy O, Potter SM. Use of infrared thermography for the assessment of free flap perforators in autologous breast reconstruction: A systematic review. JPRAS Open. 2020;23:60-70. 14. Jones NF. Intraoperative and postoperative monitoring of microsurgical free tissue transfers. Clin Plast Surg. 1992;19:783-97. 15. Holm C, Tegeler J, Mayr M, Becker A, Pfeiffer UJ, Muhlbauer W. Monitoring free flaps using laser-induced fluorescence of indocyanine green: a preliminary experience. Microsurgery. 2002;22:278-87. 16. Mothes H, Donicke T, Friedel R, Simon M, Markgraf E, Bach O. Indocyanine-green fluorescence video angiography used clinically to evaluate tissue perfusion in microsurgery. J Trauma. 2004;57:1018-24. 17. Khouri RK. Avoiding free flap failure. Clin Plast Surg. 1992;19:773-81.

146 Dynamic infrared thermography (DIRT) in DIEP flap breast reconstruction

18. Salmi AM, Tukiainen E, Asko-Seljavaara S. Thermographic mapping of perforators and skin blood flow in the free transverse rectus abdominis musculocutaneous flap. Ann Plast Surg. 1995;35:159-64. 19. John HE, Niumsawatt V, Rozen WM, Whitaker IS. Clinical applications of dynamic infrared thermography in plastic surgery: a systematic review. Gland Surg. 2016;5:122-32. 20. Thiessen FEF, Tondu T, Vermeersch N, Cloostermans B, Lundahl R, Ribbens B, et al. Dynamic infrared thermography (DIRT) in Deep Inferior Epigastric Perforator (DIEP) flap breast reconstruction: standardization of the measurement set-up. Gland Surg. 2019;8:799-805. 21. Uppal RS, Casaer B, Van Landuyt K, Blondeel P. The efficacy of preoperative mapping of perforators in reducing operative times and complications in perforator flap breast reconstruction. J Plast Reconstr Aesthet Surg. 2009;62:859-64. 22. Weum S, Mercer JB, de Weerd L. Evaluation of dynamic infrared thermography as an alternative to CT angiography for perforator mapping in breast reconstruction: a clinical study. BMC Med Imaging. 2016;16:43. 23. Bolrand d, Taylor II R. Rainbow color map (still) considered harmful. IEE computer graphics and Applications 2007;27. 24. Itoh Y, Arai K. The deep inferior epigastric artery free skin flap: anatomic study and clinical application. Plast Reconstr Surg. 1993;91:853-63; discussion 64. 25. de Weerd L, Miland AO, Mercer JB. Perfusion dynamics of free DIEP and SIEA flaps during the first postoperative week monitored with dynamic infrared thermography. Ann Plast Surg. 2009;62:42-7. 26. Blondeel PN, Beyens G, Verhaeghe R, Van Landuyt K, Tonnard P, Monstrey SJ, et al. Doppler flowmetry in the planning of perforator flaps. Br J Plast Surg. 1998;51:202-9. 27. Keys KA, Louie O, Said HK, Neligan PC, Mathes DW. Clinical utility of CT angiography in DIEP breast reconstruction. J Plast Reconstr Aesthet Surg. 2013;66:e61-5. 28. Mathes D, Keys S, Said H, Louie O, Neligan P. The clinical utility of CT angiography in deep inferior epigastric perforator (DIEP) flap microsurgical breast reconstruction. Proceedings world congress reconstructive surgery Helsinki. 2011. 29. Cina A, Salgarello M, Barone-Adesi L, Rinaldi P, Bonomo L. Planning breast reconstruction with deep inferior epigastric artery perforating vessels: multidetector CT angiography versus color Doppler US. Radiology. 2010;255:979-87. 30. Whitaker IS, Lie KH, Rozen WM, Chubb D, Ashton MW. Dynamic infrared thermography for the preoperative planning of microsurgical breast reconstruction: a comparison with CTA. J Plast Reconstr Aesthet Surg. 2012;65:130-2. 31. Li K, Zhang Z, Nicoli F, D'Ambrosia C, Xi W, Lazzeri D, et al. Application of Indocyanine Green in Flap Surgery: A Systematic Review. J Reconstr Microsurg. 2018;34:77-86.

147

General discussion General discussion: Contents

Breast cancer 151 Breast cancer reconstruction 151 Imaging during all phases of breast reconstructions with DIEP flaps: our experience with the use of DIRT 152 Comparison of techniques pre, per and postoperatively 152 A new standardized measurement set-up for the use of DIRT 153 Our experience with DIRT during all phases of breast reconstruction 154 Preoperative 154 Peroperative phase 155 Post-operative phase 156

Future perspectives 157 References 158 General discussion

Breast cancer

reast cancer is the most common cancer in women with more than two million new cases in 2018 [1]. Continuous improvement of breast cancer treatment gives a 5-year and 10-year survival of respectively 91% and 85,2% in Belgium [2]. Meaning Bbreast cancer patients in general have a good prognosis and a long-term survival. Therefore, it is important that the treatment does not focus only on survival but also on the quality of life (QOL). Reconstruction following mastectomy offers women an opportunity to improve some of the emotional and aesthetic effects of this disease. For this reason, microsurgical breast reconstructions with perforator flaps are reimbursed by the Belgian national health insurance since 2016 [3].

Breast cancer reconstruction

Chapter 1 describes breast reconstructions after breast cancer treatment. Autologous tissue transfer facilitates the primary goals of breast reconstruction. These include creation of a mound that matches preoperative dimensions, position and contour. The reconstructed breast with autologous tissue has a natural consistency and is long lasting. Autolo- gous breast-reconstruction is the technique associated with the highest patient satisfaction and represents the preferred technique for recreation of the breast [4, 5]. Evolution in microsurgery now allows transplantation of large volumes of autologous tissue from an anatomically remote area [6]. In chapter 2 we describe a historical overview of breast reconstructions with free flaps. Over the last four decades a tremendous evolution has been seen in this part of the reconstructive surgery. Autologous breast reconstructions with free flaps evolved from prolonged and laborious procedures with only limited free flaps available, to widespread surgeries with an availability of numerous potential free flaps to use. Over the years, the Deep Inferior Epigastric artery Perforator (DIEP) flap has become the gold standard for autologous breast reconstruction [7-10]. In general, the abdominal donor site was already established in breast reconstruction for its volume, color and texture resemblance with native breast tissue and for its potency to match a ptotic opposite breast that tends to age in a natural fashion. Therefore attention shifted to decreasing donor site morbidity. This was seen over the years by altering techniques from pedicled to free Transverse Rectus Abdominis muscle (TRAM) flap, to free Muscle Sparing

151151 General discussion

Transverse Rectus Abdominis muscle (MS TRAM) flap, DIEP flap and Super- ficial Inferior Epigastric Artery (SIEA) flap. Progress comes at a price however. Due to the increased complexity of dissection of perforator flaps such as the DIEP flap, a higher risk for (partial) flap failure, venous congestion and fat necrosis is observed [11, 12]. Selection of the best perforator vessels is of main importance in perforator flap surgery. This will reduce operative time, lower complication rates and ensure an overall better result [13].

Imaging during all phases of breast reconstructions with DIEP flaps: our experience with the use of DIRT

Comparison of techniques pre, per and postoperatively

The current gold standard to map the perforators is Computed Tomog- raphy Angiography (CTA) on which the location and hemodynamic properties of the flap can be assessed [14-16]. CTA replaced Color Doppler Ultra- sound (CDU). CDU is a safe and cheap technique that gives information on the diameter and blood flow characteristics of the perforator vessels, but is has to deal with a high inter-observer variability and a high number of false positives compared to CTA [14, 15, 17-20]. Moreover, it is a very time consuming examination. CTA is now frequently used because it is non-invasive and has a high spatial resolution with visualization of the intramuscular course of the vessels. However, this technique has disadvantages, such as the use of intravenous (IV) contrast agents and ionizing radiation, high purchasing costs, a lack of perioperative usability, and a lack of physiological information on flow characteristics of perforators (Table 6.1) [14]. As described in chapter 3 Dynamic Infrared Thermography (DIRT)

Table 6.1. Comparison of various tools for assessing characteristics of the perforators. CDU CTA DIRT Cost Cheap Expensive Cheap Radiation and Contrast No Yes No Easy to perform and interpret by surgeon No No Yes Operator dependent Yes No No Time Consuming Yes Yes No Applicable in all phases of DIEP No No Yes Information on flow (physiology) Yes No Yes Information on Perfusion No No Yes 3D images No Yes No Precise anatomical Description (Morphology) No Yes No

152 General discussion

has gained in popularity over the last years as an alternative technique in perforator mapping. DIRT is less invasive than CTA because it does not use radiation nor contrast agents. It is based on measurements of heat emission by tissues and skin temperature with the use of infrared (IR)-cameras. Data obtained with DIRT can be used to generate color-coded maps that strongly correlate to the perfusion of the skin. DIRT is generally used as a dynamic investigation technique, meaning that the skin must undergo a thermal cold challenge. After this cold challenge, DIRT measures the rate and patterns of rewarming. With this method, clinicians are able to identify the most dominant perforators and their perfusion area [21, 22]. Ear- lier studies have shown that DIRT can be a valuable addition during breast reconstructions with DIEP flaps. DIRT is a quick imaging technique that is available pre-, per-, and post-operatively [18, 19, 22-27]. DIRT is a valuable alternative to clinical examination to evaluate at any stage during surgery the perfusion of the flap [16]. DIRT can also be an interesting alternative to the use of indocyanine green (ICG) to evaluate the microcirculation and perfusion of the flap peroperatively. DIRT is less invasive than the use of indocyanine green because there is no need for contrast agents. Moreover the potential allergic reactions to ICG should be taken into consideration [28]. Furthermore, DIRT is easy to interpret and has a low purchasing cost. On the other hand, DIRT only provides information on the physiology of the perforator and not on the morphology [21]. When applying DIRT in a clinical setting, there a lot of factors to take into account. The choice of cameras, software, and cooling methods are crucial for successful measurements. In medical literature the description of the measurement set-up for DIRT is very diverse [27]. Only a standardized and reproducible measurement set-up will improve the quality of the measured data and will make comparisons between subjects or studies possible.

A new standardized measurement set-up for the use of DIRT

In literature multiple strategies are described, but none of them is usable in all phases of breast reconstructions. In chapter 4 we describe a new and standardized measurement method for the use of DIRT in the pre-, per- and post-operative setting without disturbing the operating surgeon [18, 19, 22-24, 26, 29, 30]. The introduction of the cold challenge is very variable in literature. The use of a desktop fan to blow air over the abdomen is described to introduce a cold challenge [21, 22, 24, 31, 32]. The difficulty with using a cold air stream is to obtain an even and homogenous cooling of the abdomen. Furthermore, the cooling capacity of cold air is

153 General discussion

lower than that of cold water. This can potentially cause bigger hotspots and complicate pinpointing the exact location of perforators. In addition to this, cooling with a desktop fan is impossible in the operation room. Another technique is the use of a metal plate to introduce a cold challenge peroperatively [22]. This metal plate only allows cooling of a small area and does not follow the curve of the abdomen. In our new and standardized measurement set-up, a sterile bag with cold water is used because it can be shaped according to the contour of the abdomen and due to its ability to evenly cool the whole area of interest. Moreover, the use of the bag with water is possible during all moments of the surgical procedure. Our choice for a 3-minute cooling period instead of 10 minutes cooling prevents potential tissue damage. A prolonged exposure of the abdomen to cold temperatures may cause damage to the subdermal plexus and diminish the visibility of hotspots [26, 29, 33]. Positioning of the camera is very variable in literature. To obtain non- disturbed pictures of the abdomen the IR-camera should be positioned perpendicular to the abdominal area. In order to obtain this perpendicular position above the abdomen of the patient, we use a tripod with an arm length of 250 cm including a counterweight. The tripod can be placed at the foot end of the operation table to prevent interference with the operating surgeon. The tripod is mounted on wheels to enable manoeuvring during surgery. To ensure every measurement has the exact same camera position relative to the operation table or bed, markings are drawn on the tripod and the ground. By using a fixed position of the camera in the perpendicular position, the images will not be distorted and automated image analysis will be possible. In other set-ups the camera was a handheld version or the abdomen was framed under an angle [34].

Our experience with DIRT during all phases of breast reconstruction

Chapter 5 describes our experience with the new standardized measurement set-up in 33 breast reconstructions with DIEP flaps in 21 patients. This measurement set-up can be used during all phases of the reconstruction and does not interfere with the operating surgeon [30].

Preoperative Preoperative selection of the perforator is mandatory in order to reduce operative time, lower complication rates and ensure an overall better result [35, 36]. CTA is the current gold standard for perforator mapping. It provides an anatomical description on the caliber, location and intramus-

154 General discussion

cular course of each perforator [37]. Some authors warn to solely rely on CTA-perforator-mapping, as they had to make multiple changes intraop- eratively in perforator selection [38]. CTA provides no physiological information of the perforators and leads to false positive results when not compared to other imaging methods. This can be due to the fact that the size of a vessel on CTA is the sum of the diameters of the perforating artery and vein [39]. Other disadvantages of CTA are the exposure to ionizing radiation, high costs and the use of contrast. DIRT can provide additional information on the localization and quality of the perforators detected on the CTA [19, 24, 26]. DIRT not only evaluates the location of the perforator but also the rate of rewarming and the progression of the hotspot. Rapid rewarming of the hotspot shows a perforator that is capable to transport more warm blood to the surface. A hotspot with rapid progression suggests a better vascular network. In our study all the perforators that where marked on the abdomen, are confirmed by a hotspot during DIRT. In 2 patients with very small perforators (<1mm) on CTA, DIRT revealed a hotspot with good rewarming and good progression of the hotspot. During dissection the perforator revealed to be usable and the reconstruction could be performed successfully. To perform these measurements efficiently, the set-up is done before the surgery starts. The first measurement is performed after induction of the patient, during further installation of the patient by the anesthesiologist. This prevents the patient of an extra visit to the hospital and prevents prolongation of the surgical procedure. Our study confirms that DIRT is capable to confirm the location of perforators of DIEP-flaps preoperatively [19, 24, 26]. Moreover, by the use of DIRT extra information on the quality of the perforators is obtained. By combining DIRT and CTA-examinations one can have best of both worlds.

Peroperative phase Peroperative monitoring of a DIEP-flap is mandatory to prevent flap failure [40]. Intraoperative evaluation of flap viability is routinely assessed by evaluating skin turgor, color, capillary refill and dermal edge bleeding. These methods are subjective and have a learning curve. More objective techniques as indocyanine-green angiography (ICG) have been proposed. Although ICG-angiography provides an objective assessment of the perfusion, the costs are high and the repeated injection with the fluorescent dye gives a potential risk of allergic reactions [28]. We have used DIRT as an alternative peroperative method for objective monitoring of flap perfusion with the same standardized measurement set-up [22]. The cost of a reli-

155 General discussion

able IR-camera is less than €20.000. The first DIRT measurement is performed after dissection of the chosen perforators. Cooling is necessary because the flap is continuously perfused by the perforator. In all patients, rapid rewarming at the location of the perforators was seen. In flaps where multiple perforators were dissected the impact of each perforator on the perfusion is evaluated by alternate clamping of the perforators. Subsequently, the perforator with the largest perfusion area is selected. The dissection of the DIEP-flap requires microsurgical skills and damage during surgery is inevitable. During dissection of one flap the pre-operatively chosen perforator was severely damaged. Immediate infrared-thermography was performed and showed rewarming of the flap through other, still intact perforators. The decision was made to harvest a free MS-TRAM. No flap-related complications and an excellent surgical result were seen postoperatively. The location of the initially visualised hotspots matched the location of the perforators after dissection in all patients except for one in which a TRAM-flap was used (the perforators were not visualized). The next challenging step is the anastomosis between the pedicle and the internal mammary vessels. We successfully used DIRT for peroperative monitoring of reperfusion with the same measurement set-up. The non-perfused flap during the microvascular anastomosis cools down which means that a thermal challenge is not necessary. In 32 flaps, rapid rewarming of the flap was seen after opening the anastomosis. This rewarming pattern was similar to the pattern seen on the abdomen. In one patient no rapid rewarming was monitored due to vasospasm and kinking of the pedicle. The absence of rewarming was noticed instantly after opening the anastomosis, before clinical signs were present. Immediately after correction of the kinking a dramatic improvement of rewarming was seen. This technique allows for an early detection of vascularization. No early venous or arterial thrombosis were seen in these 33 flaps. The final DIRT measurement is performed after flap-inset and shaping. During shaping the pedicle can potentially be compressed or kinked. DIRT detects vascularization problems before they become clinically obvious. In all our patients a fast and overall rewarming was seen.

Post-operative phase In 2 flaps we performed measurements on the ward. These flaps showed rapid and overall rewarming after cold challenge. These preliminary results show that DIRT can be a valuable tool in the postoperative monitoring of DIEP-flaps, although a larger study is needed to confirm this.

156 General discussion

Future perspectives

Our studies show that DIRT is a promising technique for selecting perforators and monitoring flap perfusion, used during all phases of breast reconstructions with one standardized measurement setup. Further randomized controlled trials are planned to assess the clinical outcome and cost-effectiveness of breast reconstructions with DIEP-flaps using DIRT. For flap studies, the pig is considered to be the best animal modal due to its similar anatomical and physiological features. Earlier studies of flap models in pigs have confirmed that the anatomy and vascularisation for the most widely used types of flaps are similar to the human counterpart [17, 41-43]. We obtained ethical approval to assess the use of DIRT in a porcine perforator flap model. With the data obtained from this animal study we, in collaboration with the engineers of the Op3Mech group of the University of Antwerp, will develop a mathematical model of the abdominal flap to gain a better understanding of the cooling and heating process of the abdominal flap. Studies to evaluate the use of Infrared Thermography in de diagnosis of skin cancer and breast cancer are prepared.

Thermography will remain a “hot” topic in future!

157 General discussion

References

1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424. 2. Cancer Burden in Belgium, https://kankerregister.org/media/docs/CancerBurdenfeb2020re- duced.pdf. 2020. 3. www.inami.fgov.be/SiteCollectionDocuments/overeenkomst_borstreconstructie_2016.pdf 4. Macadam SA, Bovill ES, Buchel EW, Lennox PA. Evidence-Based Medicine: Autologous Breast Reconstruction. Plast Reconstr Surg. 2017;139:204e-29e. 5. Serletti JM, Fosnot J, Nelson JA, Disa JJ, Bucky LP. Breast reconstruction after breast cancer. Plast Reconstr Surg. 2011;127:124e-35e. 6. Mavrogenis AF, Markatos K, Saranteas T, Ignatiadis I, Spyridonos S, Bumbasirevic M, et al. The history of microsurgery. Eur J Orthop Surg Traumatol. 2019;29:247-54. 7. Hamdi M, Weiler-Mithoff EM, Webster MH. Deep inferior epigastric perforator flap in breast reconstruction: experience with the first 50 flaps. Plast Reconstr Surg. 1999;103:86-95. 8. Blondeel PN. One hundred free DIEP flap breast reconstructions: a personal experience. Br J Plast Surg. 1999;52:104-11. 9. Keller A. The deep inferior epigastric perforator free flap for breast reconstruction. Ann Plast Surg. 2001;46:474-9; discussion 9-80. 10. Nahabedian MY, Momen B, Galdino G, Manson PN. Breast Reconstruction with the free TRAM or DIEP flap: patient selection, choice of flap, and outcome. Plast Reconstr Surg. 2002;110:466- 75; discussion 76-7. 11. Kroll SS. Fat necrosis in free transverse rectus abdominis myocutaneous and deep inferior epigastric perforator flaps. Plast Reconstr Surg. 2000;106:576-83. 12. Blondeel PN, Arnstein M, Verstraete K, Depuydt K, Van Landuyt KH, Monstrey SJ, et al. Venous congestion and blood flow in free transverse rectus abdominis myocutaneous and deep inferior epigastric perforator flaps. Plast Reconstr Surg. 2000;106:1295-9. 13. Dancey A, Blondeel PN. Technical tips for safe perforator vessel dissection applicable to all perforator flaps. Clin Plast Surg. 2010;37:593-606, xi-vi. 14. Mohan AT, Saint-Cyr M. Advances in imaging technologies for planning breast reconstruction. Gland Surg. 2016;5:242-54. 15. Nahabedian MY. Overview of perforator imaging and flap perfusion technologies. Clin Plast Surg. 2011;38:165-74. 16. Thiessen FEF, Tondu T, Cloostermans B, Dirkx YAL, Auman D, Cox S, et al. Dynamic InfraRed Thermography (DIRT) in DIEP-flap breast reconstruction: A review of the literature. Eur J Obstet Gynecol Reprod Biol. 2019;242:47-55. 17. Muntean MV, Strilciuc S, Ardelean F, Pestean C, Lacatus R, Badea AF, et al. Using dynamic infrared thermography to optimize color Doppler ultrasound mapping of cutaneous perforators. Med Ultrason. 2015;17:503-8.

158 General discussion

18. Tenorio X, Mahajan AL, Elias B, van Riempst JS, Wettstein R, Harder Y, et al. Locating perforator vessels by dynamic infrared imaging and flow Doppler with no thermal cold challenge. Ann Plast Surg. 2011;67:143-6. 19. de Weerd L, Weum S, Mercer JB. The value of dynamic infrared thermography (DIRT) in perfora- torselection and planning of free DIEP flaps. Ann Plast Surg. 2009;63:274-9. 20. Giunta RE, Geisweid A, Feller AM. The value of preoperative Doppler sonography for planning free perforator flaps. Plast Reconstr Surg. 2000;105:2381-6. 21. de Weerd L, Mercer JB, Weum S. Dynamic infrared thermography. Clin Plast Surg. 2011;38:277- 92. 22. de Weerd L, Mercer JB, Setsa LB. Intraoperative dynamic infrared thermography and free-flap surgery. Ann Plast Surg. 2006;57:279-84. 23. de Weerd L, Miland AO, Mercer JB. Perfusion dynamics of free DIEP and SIEA flaps during the first postoperative week monitored with dynamic infrared thermography. Ann Plast Surg. 2009;62:42-7. 24. Weum S, Mercer JB, de Weerd L. Evaluation of dynamic infrared thermography as an alternative to CT angiography for perforator mapping in breast reconstruction: a clinical study. BMC Med Imaging. 2016;16:43. 25. Weum S, Lott A, de Weerd L. Detection of Perforators Using Smartphone Thermal Imaging. Plast Reconstr Surg. 2016;138:938e-40e. 26. Whitaker IS, Lie KH, Rozen WM, Chubb D, Ashton MW. Dynamic infrared thermography for the preoperative planning of microsurgical breast reconstruction: a comparison with CTA. J Plast Reconstr Aesthet Surg. 2012;65:130-2. 27. John HE, Niumsawatt V, Rozen WM, Whitaker IS. Clinical applications of dynamic infrared thermography in plastic surgery: a systematic review. Gland Surg. 2016;5:122-32. 28. Li K, Zhang Z, Nicoli F, D'Ambrosia C, Xi W, Lazzeri D, et al. Application of Indocyanine Green in Flap Surgery: A Systematic Review. J Reconstr Microsurg. 2018;34:77-86. 29. de Weerd L, Weum S, Mercer JB. Dynamic Infrared Thermography (DIRT) in the preoperative, intraoperative and postoperative phase of DIEP flap surgery. J Plast Reconstr Aesthet Surg. 2012;65:694-5; author reply 5-6. 30. Thiessen FEF, Tondu T, Vermeersch N, Cloostermans B, Lundahl R, Ribbens B, et al. Dynamic infrared thermography (DIRT) in Deep Inferior Epigastric Perforator (DIEP) flap breast reconstruction: standardization of the measurement set-up. Gland Surg. 2019;8:799-805. 31. de Weerd L, Weum S, Mercer JB. Detection of perforators using thermal imaging. Plast Reconstr Surg. 2014;134:850e-1e. 32. de Weerd L, Weum S, Mercer JB. Locating perforator vessels by dynamic infrared imaging and flow Doppler with no thermal cold challenge. Ann Plast Surg. 2014;72:261. 33. Zetterman E, Salmi A, Suominen S, Karonen A, Asko-Seljavaara S. Effect of cooling and warming on thermographic imaging of the perforating vessels of the abdomen. European journal of plastic surgery. 1999;22:58-61. 34. Walle L, Fansa H, Frerichs O. [Smartphone-based thermography for perforator localisation in microvascular breast reconstruction]. Handchir Mikrochir Plast Chir. 2018;50:111-7.

159 General discussion

35. Uppal RS, Casaer B, Van Landuyt K, Blondeel P. The efficacy of preoperative mapping of perforators in reducing operative times and complications in perforator flap breast reconstruction. J Plast Reconstr Aesthet Surg. 2009;62:859-64. 36. Blondeel PN, Beyens G, Verhaeghe R, Van Landuyt K, Tonnard P, Monstrey SJ, et al. Doppler flowmetry in the planning of perforator flaps. Br J Plast Surg. 1998;51:202-9. 37. Keys KA, Louie O, Said HK, Neligan PC, Mathes DW. Clinical utility of CT angiography in DIEP breast reconstruction. J Plast Reconstr Aesthet Surg. 2013;66:e61-5. 38. Mathes D, Keys S, Said H, Louie O, Neligan P. The clinical utility of CT angiography in deep inferior epigastric perforator (DIEP) flap microsurgical breast reconstruction. Proceedings world congress reconstructive surgery Helsinki. 2011. 39. Cina A, Salgarello M, Barone-Adesi L, Rinaldi P, Bonomo L. Planning breast reconstruction with deep inferior epigastric artery perforating vessels: multidetector CT angiography versus color Doppler US. Radiology. 2010;255:979-87. 40. Khouri RK. Avoiding free flap failure. Clin Plast Surg. 1992;19:773-81. 41. Bodin F, Diana M, Koutsomanis A, Robert E, Marescaux J, Bruant-Rodier C. Porcine model for free-flap breast reconstruction training. J Plast Reconstr Aesthet Surg. 2015;68:1402-9. 42. Zotterman J, Tesselaar E, Farnebo S. The use of laser speckle contrast imaging to predict flap necrosis: An experimental study in a porcine flap model. J Plast Reconstr Aesthet Surg. 2019;72:771-7. 43. Zotterman J, Bergkvist M, Iredahl F, Tesselaar E, Farnebo S. Monitoring of partial and full venous outflow obstruction in a porcine flap model using laser speckle contrast imaging. J Plast Recon- str Aesthet Surg. 2016;69:936-43.

160 Summary

elgium is the country with the highest incidence rates of breast cancer in the world, with around 11.000 new patients every year [1, 2]. Amputation of the breast is often part of the treatment for breast cancer. As as plastic and reconstructive surgeon, I am Bresponsible for breast reconstructions in our multidisciplinary breast clinic. These reconstructions help our patients to soften some emotional and aesthetic effects of the breast cancer treatment.

In chapter 1 and 2 of this doctoral thesis we give an overview of commonly used techniques in breast reconstructions and the evolution of free flap reconstructions over time. Over the years there has been a tremendous evolution in breast reconstructions with free flaps, with the focus on reduction of donor site morbidity. Resulting in the use of perforator flaps. Breast reconstructions with Deep Inferior Epigastric artery Perforator (DIEP) flaps have become the gold standard in our department [3-5]. As this flap is only perfused by a single perforator, the selection of the perforator is of main importance. Computed Tomography Arteriography (CTA) is the gold standard for selection of the perforators [6, 7]. Not only the selection of the perforators is mandatory for successful breast-reconstructions with free flaps. Flap failure in breast reconstructions is often due to technical failures during the dissection of the perforator, failure of the anastomosis or due to kinking or compression of the pedicle during flap-inset and shaping. Clinical monitoring is mostly used to diagnose these problems [8].

In chapter 3, 4 and 5 of this doctoral thesis we evaluate the use of Dy- namic Infrared Thermography (DIRT) during breast reconstructions as a non-invasive examination that is applicable during all phases of breast reconstructions. DIRT uses a thermal challenge to rule out interference from vascular patterns in the human body and measures the rate and pattern of rewarming after this challenge. This technique allows to identify the most dominant perforators and the area they perfuse [9-13]. In literature multiple strategies are described, but none of them is usable in all phases of breast reconstructions. We describe a new and standardized measurement method for the use of DIRT in the pre-, per- and post-operative setting Summary

without disturbing the operating surgeon [10, 11, 14-19]. In our new and standardized measurement set-up, a sterile bag with cold water is used because it follows the contour of the abdomen and due to its ability to evenly cool the whole area of interest. Moreover, the use of the bag with water is possible during all moments of the surgical procedure [15, 18, 20]. In order to obtain non-disturbed images we position the IR camera in a perpendicular position above the abdomen of the patient, we use a tripod which is placed at the foot end of the operation table to prevent interference with the operating surgeon [19, 21] . In the clinical papers DIRT is used during all phases of 33 breast reconstructions with DIEP flaps in 21 patients. Our study confirms that DIRT is capable to confirm the location of perforators of DIEP-flaps preoperatively [11, 17, 18]. Moreover by the use of DIRT extra information on the quality of the perforators is obtained. Peroperatively we use DIRT as an alternative method for objective monitoring of flap perfusion with the same standardized measurement set-up [10]. We show that DIRT can be a valuable tool in the postoperative monitoring of DIEP-flaps.

162 Summary

References

1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424. 2. World Cancer Research Fund AifCR. Breast Cancer statistics. 2019. 3. Blondeel PN. One hundred free DIEP flap breast reconstructions: a personal experience. Br J Plast Surg. 1999;52:104-11. 4. Healy C, Allen RJ, Sr. The evolution of perforator flap breast reconstruction: twenty years after the first DIEP flap. J Reconstr Microsurg. 2014;30:121-5. 5. Tondu T, Tjalma WAA, Thiessen FEF. Breast reconstruction after mastectomy. Eur J Obstet Gy- necol Reprod Biol. 2018;230:228-32. 6. Rozen WM, Garcia-Tutor E, Alonso-Burgos A, Acosta R, Stillaert F, Zubieta JL, et al. Planning and optimising DIEP flaps with virtual surgery: the Navarra experience. J Plast Reconstr Aesthet Surg. 2010;63:289-97. 7. Mohan AT, Saint-Cyr M. Advances in imaging technologies for planning breast reconstruction. Gland Surg. 2016;5:242-54. 8. Khouri RK. Avoiding free flap failure. Clin Plast Surg. 1992;19:773-81. 9. de Weerd L, Mercer JB, Weum S. Dynamic infrared thermography. Clin Plast Surg. 2011;38:277- 92. 10. de Weerd L, Mercer JB, Setsa LB. Intraoperative dynamic infrared thermography and free-flap surgery. Ann Plast Surg. 2006;57:279-84. 11. de Weerd L, Weum S, Mercer JB. The value of dynamic infrared thermography (DIRT. in perfora- torselection and planning of free DIEP flaps. Ann Plast Surg. 2009;63:274-9. 12. Thiessen FEF, Tondu T, Cloostermans B, Dirkx YAL, Auman D, Cox S, et al. Dynamic InfraRed Thermography (DIRT) in DIEP-flap breast reconstruction: A review of the literature. Eur J Obstet Gynecol Reprod Biol. 2019;242:47-55. 13. Hennessy O, Potter SM. Use of infrared thermography for the assessment of free flap perforators in autologous breast reconstruction: A systematic review. JPRAS Open. 2020;23:60-70. 14. de Weerd L, Miland AO, Mercer JB. Perfusion dynamics of free DIEP and SIEA flaps during the first postoperative week monitored with dynamic infrared thermography. Ann Plast Surg. 2009;62:42-7. 15. de Weerd L, Weum S, Mercer JB. Dynamic Infrared Thermography (DIRT) in the preoperative, intraoperative and postoperative phase of DIEP flap surgery. J Plast Reconstr Aesthet Surg. 2012;65:694-5; author reply 5-6. 16. Tenorio X, Mahajan AL, Elias B, van Riempst JS, Wettstein R, Harder Y, et al. Locating perforator vessels by dynamic infrared imaging and flow Doppler with no thermal cold challenge. Ann Plast Surg. 2011;67:143-6.

163 Summary

17. Weum S, Mercer JB, de Weerd L. Evaluation of dynamic infrared thermography as an alternative to CT angiography for perforator mapping in breast reconstruction: a clinical study. BMC Med Imaging. 2016;16:43. 18. Whitaker IS, Lie KH, Rozen WM, Chubb D, Ashton MW. Dynamic infrared thermography for the preoperative planning of microsurgical breast reconstruction: a comparison with CTA. J Plast Reconstr Aesthet Surg. 2012;65:130-2. 19. Thiessen FEF, Tondu T, Vermeersch N, Cloostermans B, Lundahl R, Ribbens B, et al. Dynamic infrared thermography (DIRT) in Deep Inferior Epigastric Perforator (DIEP) flap breast reconstruction: standardization of the measurement set-up. Gland Surg. 2019;8:799-805. 20. Zetterman E, Salmi A, Suominen S, Karonen A, Asko-Seljavaara S. Effect of cooling and warming on thermographic imaging of the perforating vessels of the abdomen. European journal of plastic surgery. 1999;22:58-61. 21. Walle L, Fansa H, Frerichs O. [Smartphone-based thermography for perforator localisation in microvascular breast reconstruction]. Handchir Mikrochir Plast Chir. 2018;50:111-7.

164 Samenvatting

elgië is het land met de hoogste incidentie van borstkanker, ons land telt ongeveer 11.000 nieuwe patiënten per jaar [1, 2]. Een borstamputatie is een belangrijk onderdeel van de borstkanker- behandeling. Als plastisch en reconstructief chirurg zorg ik samen Bmet het multidisciplinair borstkliniekteam voor de patiënten die een borstreconstructie wensen te ondergaan. Deze borstreconstructies verzachten de emotionele en esthetische littekens die patiënten met borstkanker ten gevolge van hun kankerbehandeling kregen.

Hoofdstuk 1 van deze doctoraatsthesis geeft een overzicht van de meest gebruikte borstreconstructie-technieken anno 2020. In hoofstuk 2 wordt de evolutie van borstreconstructies met vrije flappen in overzicht gebracht. De borstreconstructie technieken evolueerden substantieel de laatste jaren, waarbij de focus voornamelijk lag op het verbeteren van de donorsite-morbiditeit. Deze evolutie resulteerde in de ontwikkeling van de perforator flappen. Binnen onze medische dienst zijn de borstreconstructies met Deep Infe- rior Epigastric artery Perforator (DIEP) flappen de gouden standaard [3-5]. De selectie van de juiste perforant is de basis van deze techniek, aangezien de flap enkel bevloeid wordt door één enkele perforant. Computed Tomo- graphy Arteriography (CTA) is de standaard techniek om de perforanten aan te duiden [6, 7]. Uiteraard is niet enkel de selectie van de juiste perforant noodzakelijk om een borstreconstructie met vrije flappen succesvol uit te voeren. Het falen van de DIEP flap kan een gevolg zijn van: technische problemen tijdens de dissectie van de perforant, problemen met de vaat- anastomose of complicaties ten gevolge van compressie of het knikken van de vaatsteel tijdens het vormgeven en inhechten van de flap. Klinisch onderzoek wordt meestal gebruikt om de slechte doorbloeding ten gevolge van deze problemen te diagnosticeren [8].

In hoofdstuk 3, 4 en 5 van deze doctoraatsthesis onderzoeken we het gebruik van Dynamic InfraRed Thermography (DIRT) tijdens alle fasen van borstreconstructies met DIEP-flappen als een niet-invasief onderzoek. In- frarood (IR) thermografie meet de lichaamsoppervlakte temperatuur. In Samenvatting

DIRT wordt initieel gestart met een afkoelingsfase om de invloed van andere doorbloedingspatronen in het menselijk lichaam uit te sluiten. Na de afkoelingsfase worden de opwarmingspatronen en opwarmingssnelheden van de huid opgemeten om de huiddoorbloeding te evalueren. Met het gebruik van DIRT kunnen de dominante perforanten met bijhorende perfusie zones aangeduid worden [9-13]. Er werden verschillende meetstra- tegiën bechreven in de literatuur, maar geen enkele van deze opstellingen is bruikbaar tijdens alle fasen van borstreconstructies. We beschreven met onze onderzoeksgroep een nieuwe en gestandaardiseerde meetopstelling voor het gebruik van DIRT in de pre-, per- en post-operatieve periode. Deze opstelling stoort de chirurg op geen enkel ogenblik [10, 11, 14-18]. In deze opstelling wordt gebruik gemaakt van een steriele plastieken zak ge- vuld met koud water, deze zak volgt de contour van het abdomen en kan zo de hele zone homogeen koelen. Bovendien kan deze koeltechniek op elke ogenblik van de heelkundige ingreep gebruikt worden [15, 18, 19]. De IR camera wordt loodrecht boven het abdomen van de patiënte geplaatst om geen vervormd beeld te krijgen. Hiervoor wordt een driepoot gebruikt die aan het voeteinde van de operatietafel opgesteld wordt om interferentie met de chirurg te voorkomen [20, 21]. In onze klinische studiepaper wordt DIRT gebruikt tijdens alle fasen van 33 borstreconstructies met DIEP flappen in 21 patiënten. Onze studie be- vestigt dat DIRT de locatie van perforanten van DIEP flappen preoperatief kan aantonen [11, 17, 18]. Door het gebruik van DIRT wordt er eveneens informatie over de kwaliteit van de perforanten verkregen. Peroperatief gebruiken we DIRT als een alternatieve objectieve manier om de perfusie van de flap met dezelfde meetsetup te meten [10]. We tonen eveneens dat DIRT een interessante manier kan zijn om de DIEP flappen postoperatief te volgen.

Dit onderzoeksproject toont aan dat DIRT een interessante techniek is om perferoranten te selecteren en de perfusie van de flap objectief te volgen, dit met een gestandardiseerde meet-setup die bruikbaar is tijdens alle fasen van borstreconstructies. Gerandomiseerde studies zijn noodzakelijk om de klinische uitkomst en kosten-baten analyse van het gebruik van DIRT bij borstreconstructies met DIEP flappen te evalueren. De positieve bevindingen van dit doctoraatsproject met het gebruik van DIRT tijdens microchirurgische ingrepen heeft geleid tot het opzetten van studies die het gebruik van DIRT in andere domeinen te evalueren, zoals de detectie van huid- en borstumoren.

166 Samenvatting

Referenties

1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424. 2. World Cancer Research Fund AifCR. Breast Cancer statistics. 2019. 3. Blondeel PN. One hundred free DIEP flap breast reconstructions: a personal experience. Br J Plast Surg. 1999;52:104-11. 4. Healy C, Allen RJ, Sr. The evolution of perforator flap breast reconstruction: twenty years after the first DIEP flap. J Reconstr Microsurg. 2014;30:121-5. 5. Tondu T, Tjalma WAA, Thiessen FEF. Breast reconstruction after mastectomy. Eur J Obstet Gy- necol Reprod Biol. 2018;230:228-32. 6. Rozen WM, Garcia-Tutor E, Alonso-Burgos A, Acosta R, Stillaert F, Zubieta JL, et al. Planning and optimising DIEP flaps with virtual surgery: the Navarra experience. J Plast Reconstr Aesthet Surg. 2010;63:289-97. 7. Mohan AT, Saint-Cyr M. Advances in imaging technologies for planning breast reconstruction. Gland Surg. 2016;5:242-54. 8. Khouri RK. Avoiding free flap failure. Clin Plast Surg. 1992;19:773-81. 9. de Weerd L, Mercer JB, Weum S. Dynamic infrared thermography. Clin Plast Surg. 2011;38:277- 92. 10. de Weerd L, Mercer JB, Setsa LB. Intraoperative dynamic infrared thermography and free-flap surgery. Ann Plast Surg. 2006;57:279-84. 11. de Weerd L, Weum S, Mercer JB. The value of dynamic infrared thermography (DIRT. in perfora- torselection and planning of free DIEP flaps. Ann Plast Surg. 2009;63:274-9. 12. Thiessen FEF, Tondu T, Cloostermans B, Dirkx YAL, Auman D, Cox S, et al. Dynamic InfraRed Thermography (DIRT) in DIEP-flap breast reconstruction: A review of the literature. Eur J Obstet Gynecol Reprod Biol. 2019;242:47-55. 13. Hennessy O, Potter SM. Use of infrared thermography for the assessment of free flap perforators in autologous breast reconstruction: A systematic review. JPRAS Open. 2020;23:60-70. 14. de Weerd L, Miland AO, Mercer JB. Perfusion dynamics of free DIEP and SIEA flaps during the first postoperative week monitored with dynamic infrared thermography. Ann Plast Surg. 2009;62:42-7. 15. de Weerd L, Weum S, Mercer JB. Dynamic Infrared Thermography (DIRT) in the preoperative, intraoperative and postoperative phase of DIEP flap surgery. J Plast Reconstr Aesthet Surg. 2012;65:694-5; author reply 5-6. 16. Tenorio X, Mahajan AL, Elias B, van Riempst JS, Wettstein R, Harder Y, et al. Locating perforator vessels by dynamic infrared imaging and flow Doppler with no thermal cold challenge. Ann Plast Surg. 2011;67:143-6.

167 Samenvatting

17. Weum S, Mercer JB, de Weerd L. Evaluation of dynamic infrared thermography as an alternative to CT angiography for perforator mapping in breast reconstruction: a clinical study. BMC Med Imaging. 2016;16:43. 18. Whitaker IS, Lie KH, Rozen WM, Chubb D, Ashton MW. Dynamic infrared thermography for the preoperative planning of microsurgical breast reconstruction: a comparison with CTA. J Plast Reconstr Aesthet Surg. 2012;65:130-2. 19. Zetterman E, Salmi A, Suominen S, Karonen A, Asko-Seljavaara S. Effect of cooling and warming on thermographic imaging of the perforating vessels of the abdomen. European journal of plastic surgery. 1999;22:58-61. 20. Walle L, Fansa H, Frerichs O. [Smartphone-based thermography for perforator localisation in microvascular breast reconstruction]. Handchir Mikrochir Plast Chir. 2018;50:111-7. 21. Thiessen FEF, Tondu T, Vermeersch N, Cloostermans B, Lundahl R, Ribbens B, et al. Dynamic infrared thermography (DIRT) in Deep Inferior Epigastric Perforator (DIEP) flap breast reconstruction: standardization of the measurement set-up. Gland Surg. 2019;8:799-805.

168 Curriculum vitae

General information

Name: Thiessen Filip, Emmanuel Francis Date of Birth: 21 january, 1977 Place of Birth: Lier

Civil status: married with Katrien Smets father of Frederik and Louise

Address: Christus Koninglaan 40, BE-2640 Mortsel GSM: +32496695099 e-mail: [email protected]

Education

Secondary School

Majors in Latin-Mathematics Onze Lieve Vrouw van Lourdes College (Edegem) 1995

Medicine

University of Antwerp 1995 - 2002 Diploma in electrocardiography 2001

Clinical and scientific training 1998 Tempus Student Mobility (European Community) Jagellonian University, school of Medicine, Krakow, Poland

Internship Gynaecology and Pediatrics, 2001 Frere Hospital, East London, South-Africa Curriculum vitae

Residency in Plastic, Reconstructive and Aesthetic Surgery

Basic Surgical Training

AZ Middelheim, Antwerp 2002 - 2004 AZ Middelheim, Antwerp 2005 - 2006

Higher Surgical Training

Great Ormond Street Hospital for Sick Children 2004 - 2005 London, United Kingdom Congenital Plastic and Reconstructive Surgery

University Hospital of Ghent 2006 - 2010 Ghent, Belgium Plastic, Reconstructive and Aesthetic Surgery Head of department: Prof. Dr. S. Monstrey Staff Members: Prof. Dr. P. Blondeel, Prof. Dr. M. Hamdi, Prof. Dr. K. Van Landuyt, Dr. N. Roche

Visiting Resident Medical College of Wisconsin 2008 Dr. J. Hijjawi, Milwaukee, USA

Visiting Resident, Rhinoplasty 2010 Dr. S. Tuncer, Ankara, Turkey

Aesthetic Fellowship 2010 University of Chile, Santiago Hospital del Trabajador de Santiago Clinica Sara Moncada Santiago, Chili Dr. Patricio Andrades

Facial Aesthetic Fellowship 2010 Coupure Medical Centre, EMC2 Ghent, Belgium Dr. P. Tonnard, Dr. A. Verpaele

Primus Promovendus in Belgium, Summa cum Laude, Promotion 2010, Fellow of the Collegium Chirurgicum Plasticum (FCCP)

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Awards/grants

Tempus Student Mobility Grant (European Community) 1998 Krakow, Poland

ActUA grant for Internship South-Africa 2001

Grant Professor Guido Matton 2010 Best Scientific Publication Flap Surgery for Pressure Sores: Should the underlying muscle be transferred or not?

Professional activity

Plastic, Reconstructive and Aesthetic Surgeon at the University Hospital Antwerp (UZA), Belgium Consultant Plastic, Reconstructive and Aesthetic Surgeon of the Breast Clinic of the University Hospital Antwerp, Belgium. Head of Department of Plastic, Reconstructive and Aesthetic Surgery Ziekenhuis Netwerk Antwerpen (ZNA), Antwerp, Belgium. Plastic, Reconstructive and Aesthetic Surgeon, AZ Rivierenland, Antwerp, Belgium. Plastic, Reconstructive and Aesthetic Surgeon Private Practice Clinic 12B, Antwerp, Belgium. Head of the Plastic, Reconstructive and Aesthetic Surgery Training Program, University of Antwerp, Belgium. Member of the Chamber of Recognition Plastic, Reconstructive and Aesthetic Surgery.

Scientific publications

Blondeel PN, Hamdi M, Van de Sijpe KA, Van Landuyt KH, Thiessen FE, Monstrey SJ: The latero- central glandular pedicle technique for breast reduction. Br J Plast Surg. 2003 Jun; 56(4): 348-59 Vadodaria S, Watkin N, Thiessen F, Ponniah A.: The first cleft palate simulator. Plast Reconstr Surg. 2007 Jul; 120 (1): 259-61. Witherow H, Thiessen F, Evans R, Jones B, Hayward R, Dunaway D: Relapse following frontofacial advancement using the rigid external distractor. Journal of craniofacial surgery 2008 Jan 19(1): 113-20.

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Hamdi M, Thiessen F, Depypere H: Pedicled perforator flaps in breast surgery: a new concept. Belgian journal of medical oncology 2008: 2(5): 288-292 M. Hamdi, P. Andrades, F. Thiessen, F. Stillaert, N. Roche, K, Van Landuyt, S. Monstrey; Is a second free flap still an option in failed free flap breast reconstruction? Plast Reconstr Surg 2010 Aug; 126(2): 375-84 F. Thiessen, P. Andrades, Ph. Blondeel, M. Hamdi, F. Stillaert, K. Van Landuyt, N. Roche, S. Mon- strey: Flap surgery for pressure sores: should the underlying muscle be transferred or not? J Plast Reconstr Aesthet Surg 2011 Jan; 64(1): 84-90 M. Hamdi, B. Casaer, P. Andrades, F. Thiessen, A. Dancey, S. D’Arpa, K. Van Landuyt; Salvage (tertiary) breast reconstruction after implant failure. J Plast Reconstr Aesthet Surg 2011 Mar; 64(3): 353-9 F Thiessen, Tondu T. Een borst uit eigen weefsel. MagUZA 93, july 2013 Tondu T*, Thiessen F*, Tjalma WA: Prophylactic bilateral nipple-sparing mastectomy and a staged breast reconstruction technique: preliminary results. Breast Cancer (Auckl). 2016 nov 9; 10: 185-189. * equally contributing De Decker M, De Schrijver L, Thiessen F, Tondu T, Van Goethem M, Tjalma WA: Breast cancer and fat grafting: efficacy, safety and complications- a systematic review. Eur J Obest Gynecol Reprod Biol. 2016 Dec; 207: 100-108 Van Dorp MV, Roovers E, Tondu T, Thiessen F: Simplified penoscrotal reconstruction for extensive Fournier gangrene defects. Urol J 2016 Dec 8: 13 (6): 2917-2929 De Roeck L, Tondu T, Thiessen F: Progressive subcutaneous emphysema of unknown origin: a surgical dilemma. Acta Chir Belg. 2019 Aug;119(4):251-253. Verhoeven V, Vrints I, Thiessen F, Tondu T: A contemporary and historical patient with an ectopic meningioma. Acta Chir Belg. 2019 Aug;119(4):254-258. Thiessen FEF, Tjalma WAA, Tondu T: Breast reconstruction after breast conservation therapy for breast cancer. Eur J Obstet Gynecol Reprod Biol. 2018 Nov;230:233-238. Filip E.F. Thiessen, Nicolas Vermeersch, Wiebren A.A. Tjalma, Thierry Tondu: Borstreconstructie na borstsparende chirurgie voor borstkanker. Reconstruction mammaire après chirurgie con- servatrice pour un cancer du sein. Onco Hemato Vol 12 nr 6 2018 Filip E.F. Thiessen, Nicolas Vermeersch, Wiebren A.A. Tjalma, Thierry Tondu: Borstreconstructie na borstsparende chirurgie voor borstkanker. Reconstruction mammaire après chirurgie con- servatrice pour un cancer du sein. Gunaikeia Vol 23: nr 9:33-38 2018 Tondu T, Tjalma WAA, Thiessen FEF: Breast Reconstruction after mastectomy. Eur J Obstet Gynecol Reprod Biol. 2018 Nov;230:228-232. De Weerdt G, Verhoeven V, Vrints I, Thiessen F, Tondu T.: Elastofibroma dorsi: a case report of bilateral occurrence and review of literature. Acta Chir Belg. 2019 Jul 16:1-5. Vermeersch N, Peters B., Somville J, Van Landuyt K, Thiessen F, Tondu T: Massive femur defect after Ewing’s sarcoma resection reconstructed with a free vascularised fibular graft in a four- year-old girl. Acta Chir Belg. 2020 Jun;120(3):193-197. Vermeersch N, De Fré M, Thierry T, Thiessen F: Reply to the editor: Microsurgery training with smartphone. Handchir Mikrochir Plast Chir. 2019 Aug;51(4):336.

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Thiessen FEF, Tondu T, Cloostermans B, Dirkx Y, Auman D, Cox S, Verhoeven V, Hubens G, Steenackers G, Tjalma WAA.: Dynamic InfraRed Thermography (DIRT) in DIEP-flap breast reconstruction: A review of the literature. Eur J Obstet Gynecol Reprod Biol 2019 Nov;242:47-55. De Fré Maxime, Smets Katrien, Ulicki Michal, Verhoeven Veronique, Siozopoulou Vasiliki, Strobbe Tine, Specenier Pol, Aerts Olivier, Lambert Julien, Tondu Thierry, Thiessen Filip: Eccrine po- rocarcinoma of the scalp: diagnosis and importance of early surgical intervention. European journal of plastic surgery - ISSN 0930-343X-42:6 (2019) p. 623-627 Thiessen FEF, Tondu T, Vermeersch N, Cloostermans B, Lundahl R, Ribbens B, Berzenji L, Verhoev- en V, Hubens G, Steenackers G, Tjalma WAA. Dynamic InfraRed Thermography (DIRT) in Deep Inferior Epigastric Perforator (DIEP) flap breast reconstruction: standardization of the measurement set-up. Gland Surg. 2019 Dec;8(6):799-805. Vissers G, Van Houtven L, Corthouts J, Snoeckx A, Luijks M, Thiessen F, Tondu T, Van Schil P.: Ewing’s sarcoma of the sternum necessitating complex resection and reconstruction. Case Reports Plast Surg Hand Surg. 2019 Apr 15;6(1):125-130. Liekens E, van Sprundel F, Thiessen F, Pirenne Y. Martius flap reconstruction for rectovaginal fis- tula after stapled hemorrhoidopexy (Longo operation): a case report. Int J Colorectal Dis. 2019 Sep;34(9):1619-1623. Steenackers Gunther, Verstockt Jan, Cloostermans Ben, Thiessen Filip, Ribbens Bart, Tjalma Wiebren. Infrared thermography for DIEP flap breast reconstruction part I: Measurements. Proceedings - ISSN 2504-3900 - 27:1(2019), p. 1-5. Steenackers Gunther, Cloostermans Ben, Thiessen Filip, Dirkx Yarince, Ribbens Bart, Tjalma Wie- bren, Verstockt Jan: Infrared thermography for DIEP flap breast reconstruction part II: analysis of the results. Proceedings - ISSN 2504-3900 - 27:1(2019), p. 1-5 De Fré M, Vermeersch N, De F, Ulicki M, Smets K, Tondu T, Thiessen F.: Giant basal cell carcinoma on the forehead and why we should prevent them – case report. Acta Chir Plast. 2020 Win- ter;61(1-4):24-27. Tondu T, Hubens G, Tjalma WA, Thiessen FE, Vrints I, Van Thielen J, Verhoeven V: Breast reconstruction after nipple-sparing mastectomy in the large and/or ptotic breast: A systematic review of indications, techniques, and outcomes. J Plast Reconstr Aesthet Surg. 2020 Mar;73(3):469-485. Verstockt J*, Thiessen F*, Cloostermans B, Tjalma W, Steenackers G.: DIEP flap breast reconstructions: thermographic assistance as a possibility for perforator mapping and improvement of DIEP flap quality. Appl Opt. 2020 Jun 10;59(17):E48-E56. * equally contributing Thiessen FEF, Vermeersch N, Tondu T, Van Thielen J, Vrints I, Berzenji L, Verhoeven V, Hubens G, Verstockt J, Steenackers G, Tjalma WAA.: Dynamic infrared thermography (DIRT) in DIEP flap breast reconstruction: a clinical study with a standardized measurement setup. Eur J Obstet Gynecol Reprod Biol. 2020 Sep;252:166-173. Thiessen FEF, Tondu T, Verhoeven V, Hubens G, Steenackers G, Tjalma WAA.: Automatic detection of perforators for microsurgical reconstruction. Breast. 2020 Jun 13;53:43.

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Chapter in medical book

Moustapha Hamdi, Filip E. Thiessen: Perforator flap reconstruction of BCT deformities. Partial Breast Reconstruction, Techniques in Oncolplastic surgery, Losken and Hamdi, QMP

Promotorship for master thesis of medical students

Motivation for and against breast reconstruction after mastectomy. Student: Monique Stoop and Theodora Heringa 2014-2015 Promotor: Tjalma WA Co Promotor: Huizing M, Tondu T, Thiessen F Breast cancer and cosmetic surgery: The effect of lipofilling on outcome and follow up. Student: Bedert P, Toma N, Van Steen R 2015-2018 Promotor: Tjalma WA Co-promotor: Tondu T, Thiessen F Outcome of fat grafting in patients with a history of breast cancer: a retrospective matched cohort study. Student: De schrijver L, De Decker M 2015-2018 Promotor: Tjalma WA Co-Promotor: Van Goethem M, Tondu T, Thiessen F The use of Fluorescence scan in breast reconstructions. Student: Arkaz C, Ocak I 2015-2018 Promotor: Tjalma WA Co-promotor: Tondu T, Thiessen F Breast reconstruction with DIEP-flap: a diagnostic cohort study with a comparison between CT and DIRT. Student: Auman D., Cox S. 2018-2021 Promotor: Tjalma WA Co-promotor: Thiessen F, Steenackers G.

Presentations

Decubitus ulcer review: 1996-2002. Thiessen FE, Blondeel PN, Monstrey SJ M.D. Thesis May 2002 University of Antwerp, Belgium Ear reconstruction for ear loss in infancy F. Thiessen, D. Gault

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Oral presentation “Sixth Belgian Surgical Week” 28 – 30 April 2005, Ostend, Belgium Joint and nail preserving technique for asymmetric Wassel Type I thumb duplication in children and adults B. Oelbrandt, F. Thiessen, P. Smith Oral presentation “Lustrum meeting, Belgian Society for Plastic, Reconstructive and Aesthetic Surgery” 6 – 7 May 2005, Brussels, Belgium Ear reconstruction for traumatic ear loss in infancy F. Thiessen, D. Gault Oral presentation “Lustrum meeting, Belgian Society for Plastic, Reconstructive and Aesthetic Surgery” 6 – 7 May 2005, Brussels, Belgium Flap surgery for pressure sores: should the underlying muscle be transferred or not? F. Thiessen, Ph. Blondeel, M. Hamdi, K. Van Landuyt, N. Roche, S. Monstrey Oral presentation “EURAPS, European Association of Plastic Surgeons” 27 – 29 May 2005, Marseille, France Relapse following Monobloc advancement distraction using the RED external distractor. H. Witherow, F. Thiessen, R. Evans, R. Hayward, B. Jones, D. Dunaway Oral presentation “British Association of Oral and Maxillofacial Surgeons, Annual Scientific Meeting” 8 – 10 June 2005, Gateshead, United Kingdom First cleft palate simulator S. Vadodaria, N. Watkins, F. Thiessen Oral presentation “ 10 th International congress on cleft palate and related Craniofacial anomalies, Cleft care for all.” 4 – 8 September 2005, Durban, South Africa Perforator based V-Y advancement flaps in the reconstruction of lower limb defects after mela- noma excision in lower leg. B. Oelbrandt, F. Thiessen, NS Niranjan Oral presentation 19/11/2005: Autumn meeting 2005 of the Royal Belgian society for plastic, reconstructive and aesthetic surgery Sint-Niklaas, Belgium First cleft palate simulator S. Vadodaria, N. Watkins, F. Thiessen Oral presentation “European Association of Plastic surgeons, EURAPS” 25-27/05/06 Istanbul, Turkey Het drie-dimensioneel ‘engineeren’ van adipeus weefsel Thiessen F, Stillaert F, Blondeel Ph. Wetenschapsdag 14/03/2007 UZ Ghent Flap surgery for pressure sores: should the underlying muscle be transferred or not? F. Thiessen, Ph. Blondeel, M. Hamdi, K. Van Landuyt, N. Roche, S. Monstrey Oral presentation

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17/11/2007: Autumn meeting 2007 of the Royal Belgian society for plastic, reconstructive and aesthetic surgery Leuven, Belgium Reconstructive and Aesthetic Breast Surgery Workshop Live Surgery with Prof. M. Hamdi: Breast-reconstruction 8-9/04/2008: Saudi-Arabia Perforated non expanded skin grafts with novel 1:1 V-Carrier: A comparative study with full sheet grafts in 47 patients. A. Zeltzer, H. Hoeksema, A. Pirayesh, H. Hoekstra, S. Monstrey, F. Thiessen Oral Presentation 14 th Congress of the International Society for Burn Injuries Sept 2008, Montreal, Canada Laser Doppler imaging as a valuable tool for monitoring the ingrowth of dermal substitutes. F. Thiessen, A. Zeltzer, H. Hoeksema, A. Pirayesh, H. Hoekstra, S. Monstrey Oral Presentation 14 th Congress of the International Society for Burn Injuries Sept 2008, Montreal, Canada Bipedicled DIEP flaps for reconstruction of soft-tissue deficiencies in male patients. A L Mahajan, P Cadenelli, F Thiessen, K Van Landuyt, F Stillaert Oral Presentation BAPRAS summer meeting june 2010, Sheffield, UK Borstreconstructie in de 21ste eeuw. F Thiessen Lok vergadering huisartsenkring Brasschaat 09/09/2010 MACS lift surgery in male patients: Our experience in 50 patients F Thiessen, P Vermeulen, P Tonnard, A Verpaele Oral presentation 20/11/2010: Autumn meeting 2010 of the Royal Belgian society for plastic, reconstructive and aesthetic surgery Beersel, Belgium Borstreconstructies state of the art: Symposium “Erfelijkheid bij Borstkanker” F Thiessen: Borstreconstructie state of the art 29/01/2011: Symposium “Erfelijkheid bij Borstkanker” Symposium Multidisciplinaire borstkliniek UZA F Thiessen, T. Tondu: multipdisciplinaire aanpak borstreconstructie 15/12/2011: Symposium Multidisciplinaire borstkliniek UZA Borstheelkunde in al zijn facetten F Thiessen 20/3/2012: Lok vergadering huisartsenkring Berchem

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Symposium “Multidisciplinaire benadering en economische beschouwingen” borstkliniek ZNA Mid- delheim F Thiessen; multipdisciplinaire aanpak borstreconstructie 15/12/2011: Symposium Multidisciplinaire borstkliniek ZNA 13de Huisartsensymposium ZNA Middelheim F Thiessen: Plastische Chirurgie voor de huisarts 23/3/2012 Breast reconstruction Awareness day: Bra-day 2012 F Thiessen, T Tondu: Borstreconstructies “alle mogelijkheden” Borstreconstructie state of the art F Thiessen: Opleiding assistenten UZA 16/4/2013 Breast reconstruction state of the art. Secondary procedures in breast reconstruction. University of Antwerp, Breast Clinic F. Thiessen 16/10/2013 Symposium “Panorama op borstkanker voor de huisarts” F Thiessen: Borstreconstructies in al zijn facetten 22/06/2013: ZNA Middelheim Breast reconstruction Awareness day: Bra-day 2013 F Thiessen: Borstreconstructie dmv diep flap 16/10/2013 Breast reconstruction Awareness day: Bra-day 2014 F Thiessen: Borstreconstructie dmv diep flap: State of the Art 15/10/2014 Breast reconstruction Awareness day: Bra-day 2015 F Thiessen: Borstreconstructie dmv diep flap: Where are we now? 21/10/2015 Vlaamse Vereniging Operatie Verpleegkundigen (VVOV) 2016 F. Thiessen: Surgical treatment of Skin Tumours in the Face: state of the art 27/05/2016, Blankenberge, Belgium Breast reconstruction Awareness day: Bra-day 2016 F Thiessen: Borstreconstructie dmv diep flap 19/10/2016 Insurance Medicine and Aesthetic Evaluation, Interuniversity Postgraduate. University of Antwerp, F Thiessen 16/12/2016 Breast Reconstruction anno 2017. Naboram F Thiessen 18/05/2017 Breast reconstruction Awareness day: Bra-day 2017 F Thiessen: Borstreconstructie dmv diep flap 18/10/2017

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Insurance Medicine and Aesthetic Evaluation, Interuniversity Postgraduate. University of Antwerp, F. Thiessen 8/12/2017 Cyclus indicatieve tabel: Begroting menselijke schade in 10 Sessies. Esthetische Schade/Kapitalisatie. die Keure 20/06/2018 Filip Thiessen, Thierry Tondu Breast reconstruction Awareness day: Bra-day 2017 F Thiessen: Borstreconstructie dmv diep flap 17/10/2018 Vichy opleidingsavonden: Anti-aging training. Gent en Zelem Filip Thiessen 23/10/2018, 25/10/2018, 14/11/2018, 15/11/2018 Insurance Medicine and Aesthetic Evaluation, Interuniversity Postgraduate. University of Antwerp, F. Thiessen 22/11/2019 Microsurgery training using a smartphone N. Vermeersch, T. Tondu, F Thiessen Oral presentation 26/04/2019: Autumn meeting 2019 of the Royal Belgian society for Plastic, Reconstructive and Aesthetic surgery Waterloo, Belgium Faculty at BAU hands-on Microsurgery meeting 02- 04 may 2019: Bahcesehir University school of Medicine, Istanbul, Turkey Delayed two-stage nipple sparing mastectomy and simultaneous expander to implant reconstruction of the large and ptotic breast T. Tondu, F. Thiessen, G. Hubens, W. Tjalma, V. Verhoeven Oral presentation “EURAPS, European Association of Plastic Surgeons” 24 May 2019, Helsinki, Finland Infrared thermography for DIEP flap breast reconstruction part I: Measurements. Steenackers Gunther, Verstockt Jan, Cloostermans Ben, Thiessen Filip, Ribbens Bart, Tjalma Wiebren. Oral Presentation 17-19 September 2019: International Workshop on Advanced Infrared Technology and Applica- tions (AITA) Florence, Italy Infrared thermography for DIEP flap breast reconstruction part II: analysis of the results. Steenackers Gunther, Cloostermans Ben, Thiessen Filip, Dirkx Yarince, Ribbens Bart, Tjalma Wiebren, Verstockt Jan. Oral Presentation 17-19 September 2019: International Workshop on Advanced Infrared Technology and Applica- tions (AITA) Florence, Italy

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Poster presentations

Gebuers N, Dieben L, De Kock R, Van Breda E, Thiessen F, Tondu T, Verbelen H, Tjalma WA. Postoperative edema reduction by means of custom made compression bra for patients with breast reduction surgery. 26 th World Congress of Lymfology, 25-29/9/2017, Barcelona, Spain Vermeersch N, Tondu T, Thiessen F, Van Landuyt K, Somville J. Reconstruction of massive femur defect with a free vascularised fibular graft after Ewing’s sarcoma resection in a four-year old girl. 18 th Interantional course on Perforator Flaps, 15-18/11/2017, Ghent, Belgium Van Bergen L, Vrints I, Thiessen F, Tondu T. Periorbital necrotizing fasciitis, a rare condition. Bel- gian Surgical Week, 18-20/5/2017, Ostend, Belgium Vermeersch N, Tondu T, Thiessen F, Van Landuyt K, Somville J. Reconstruction of massive femur defect with a free vascularised fibular graft after Ewing’s sarcoma resection in a four-year old girl. Belgian Surgical Week, 18-20/5/2017, Ostend, Belgium Van Bergen L, Vrints I, Thiessen F, Tondu T. Periorbital necrotizing fasciitis, a rare condition. Ant- werp Medical Students Congress 2016, 10-13/9/2016, Antwerp Belgium Thiessen F, De Schrijver L, De Decker M, Tondu T, Van Goethem M, Tjalma W. Outcome of lipofilling in patients with a history of breast cancer: a retrospective cohort study. San Antonio Breast Cancer Symposium; 2018, San Antonio, USA

Membership

Royal Belgian Society of Surgery Royal Belgian Society for Plastic, Reconstructive and Aesthetic Surgery (RBSPRAS) International Society of Aesthetic Plastic Surgerys (ISAPS) The European Academy of Facial Plastic Surgery (EAFPS)

179

Dankwoord

eze thesis is enkel tot stand kunnen komen door de inspan- ningen en hulp van vele mensen door de jaren heen. Al deze mensen wil ik graag bedanken.

DIk wil de leden van mijn jury, Prof. Dr. Jeroen Hendriks, Prof. Dr. Manon Huizing, Prof. Dr. Emiel Rutgers en Pof. Dr. Assaf Zeltzer bedanken voor de opbouwende kritiek en vele raadgevingen die de kwaliteit van mijn thesis verbeterd hebben. Ik weet dat het begeleiden en beoordelen van een doctoraat een grote inspanning vraagt.

Mijn promotoren: Prof. Dr. Wiebren Tjalma, Prof. Dr. Gunther Steen- ackers, Prof. Dr. Guy Hubens en Prof. Dr. Veronique Verhoeven wil ik één voor één uitdrukkelijk danken voor hun hulp bij het finaliseren van dit werk. Wiebren, door uw beroep als oncologisch gynaecoloog behandelen we ondertussen al ongeveer 10 jaar samen patiënten met borstkanker. Binnen de borstkliniek maakt een goede borstreconstructie integraal deel uit van de behandeling van een borsttumor. Uw continu streven naar verbetering van de behandeling van uw patiënten bracht ons naar het gebruik van thermografie tijdens borstreconstructies. U hebt me tijdens het hele traject met uw enthousiasme blijven steunen en voortstu- wen. Elk idee, elke paper, elke presentatie wordt kritisch door U bekeken en waar nodig bijgestuurd. Uren hebben we zitten nadenken en discus- siëren hoe we het project konden verbeteren. Ik ben er zeker van dat Anne, uw fantastische vrouw, U door onze telefoontjes en meetings af en toe te lang heeft moeten missen. Sorry Anne. Wiebren ik heb U tijdens dit project nog beter leren kennen en ik apprecieer U daardoor nog veel meer. Ik beschouw U als een vriend die me raad en daad bijstaat. Ik kijk uit ernaar uit om nog meerdere studies verder af te werken en te starten! Gunther jouw expertise binnen het domein van de thermografie was van cruciaal belang voor dit project. Je leerde me een redeneren als een Dankwoord

ingenieur en ik hoop dat ik jou een beetje het medisch denken kon aan- leren. Ik kijk uit om in de toekomst samen verder onderzoek te doen. Guy, eerst en vooral wil ik U danken voor de kansen die U me bood om de Plastische Heelkunde binnen uw dienst mee verder uit te breiden tot wat het vandaag is. Uw doortastende en doelgerichte aanpak tijdens dit project waren van onnoemelijk belang. Soms begreep ik niet waar je de tijd nog haalde om dit project mee te begeleiden naast uw taken als diensthoofd in het UZA en als decaan aan de Universiteit Antwerpen. Dank je! Veronique, al jaren steun je me om het wetenschappelijke luik binnen onze dienst op een hoger niveau te brengen. Je slaagt erin om elk wetenschappelijke project of paper binnen de kortste keren te reviewen en de sterktes en de zwaktes naar voor te brengen. Je hebt me tijdens de hele periode in raad en daad bijgestaan. Dank je.

Mijn opleiders Prof. Dr. Stan Monstrey, Prof. Dr. Phillip Blondeel, Prof. Dr. Moustapha Hamdi, Prof. Dr. Koen Van Landuyt en Prof. Dr. Nathalie Roche hebben me een fantastische opleiding gegeven. Zonder deze opleiding was ik nooit de plastisch chirurg geweest die ik nu ben. Dank je.

Reconstructieve borstchirurgie is teamwerk. Soms lange dagen in het OK, met af en toe technisch moeilijke ingrepen. Iedereen die betrokken is bij deze ingrepen ben ik zeer dankbaar om me te ondersteunen en te helpen om de ingrepen tot een goed einde te brengen. Alle leden van de borstklinieken, het ganse team, dank u om er te zijn voor ons en te patiënten. Ook wil ik de patiënten danken die vertrouwen op onze dienst en ons toelaten om nieuwe technieken verder op punt te stellen.

De collega’s en directies van de ziekenhuizen wil ik danken voor de ondersteuning tijdens dit traject en de kansen die ze me boden. Dirk De Weerdt, voor de fantastische grafische ondersteuning en het hulp met de lay-out bij het afwerken van dit boek.

Kristin Deby, die me hielp en wegwijs maakte in het vervullen van de formaliteiten om dit werk tot een goed einde te maken.

182 Dankwoord

Onze assistenten in opleiding wil ik danken voor de dagelijkse inzet voor de dienst. Nicolas, jou wil ik in het bijzonder danken voor de en- thousiaste ondersteuning en kritische input tijdens dit project!

Mijn collega’s van Clinic12b; Thierry, Ina, Jana, Lynn, Sofie, Angelique, Sandra en Cindy. Samen slagen we erin een succesvolle praktijk te run- nen. Jullie zijn een echt “top team”.

Thierry, mijn collega, mijn “compagnon de route”. Toen we elkaar leerden kennen op de dienst Plastische Heelkunde van het Universitair Ziekenhuis Gent nu ongeveer 20 jaar geleden droomden we ervan samen een praktijk uit te bouwen in Antwerpen. Ik ben je oprecht dankbaar dat je me 10 jaar geleden de kans gaf om samen met jou deze droom waar te maken. Ondertussen hebben we al heel wat watertjes doorzwommen, het ene al wat dieper als het andere… Thierry niet al- leen je luisterend oor, je enthousiasme en diplomatie, maar ook je wel- gemeend advies tijdens de voorbije jaren zal ik niet vergeten: zoals ik je het al vroeger gezegd heb zie ik je als “partner in crime” maar bovenal als een vriend. Ik kijk alvast uit naar de verdediging van jouw thesis binnenkort.

Een gelukkig leven bestaat niet enkel uit een geslaagd professioneel parcours. Mijn vrienden zou ik voor geen geld willen missen. Sorry dat ik af en toe sneller weg moest of niet kon komen … sorry dat ik te laat op het appel verscheen en jullie soms met 3 moesten tennissen in plaats van 4. Dank voor jullie onvoorwaardelijke steun.

Mijn ouders, mama en papa; zonder jullie opvoeding was ik niet geweest wie ik nu ben. Jullie gaven me steeds alle kansen. Zonder jullie hulp voor Louise en Frederik had ik deze thesis nooit kunnen afwerken. Dank jullie voor alles en ik zie jullie graag.

Mijn zus en schoonbroer, Barbara en Erik; mijn schoonouders, mams en paps; mijn schoonzus en schoonbroer, Hilde en Koen; mijn schoonzus en schoonbroer, Elisabeth en Steven; zonder jullie hulp en ondersteuning was deze thesis nooit geworden wat ze nu is. Dank voor alle steun.

183 Dankwoord

Frederik en Louise, onze twee prachtige kinderen! Jullie kwamen bei- den regelmatig op mijn bureau vragen of mijn boekje nog niet af was of wat ik nu weer op de computer aan het doen was. Zoals jullie weten, is het boekje nu af en kijk ik ernaar uit om heel graag super-leuke dingen met jullie te doen. Ik ben trots op wie jullie zijn en zie jullie heel graag!

Katrien, mijn lieve, ambitieuze en verstandige vrouw. Zonder jouw steun was dit boek er nooit geweest. Je kon me steeds overtuigen om deze weg verder te volgen. Ik besef nu pas ten volle hoe moeilijk het was voor jou om jouw PhD nu ongeveer 4 jaar geleden af te ronden. Als team hebben we de voorbije jaren meerdere projecten afgewerkt. Ik kijk uit naar onze volgende projecten!

Filip

184 Louise en Frederik Thiessen 1 september 2020