Breast Reconstruction: A Century of Controversies and Progress.

Breast cancer treatment has dramatically changed over the past century. Since Halsted's first description of radical mastectomy in 1882, breast reconstruction has evolved slowly from being considered as a useless or even dangerous procedure by surgeons to the possibility nowadays of reconstructing almost any kind of defect. In this review on the development of breast reconstruction, we outline the historical milestone innovations that led to the current management of the mastectomy defect in an attempt to understand the economic, social and psychological factors, which contributed to slow down its acceptance for several decades.

Novel micropatterns mechanically control fibrotic reactions at the surface of silicone implants.

Over the past decade, various implantable devices have been developed to treat diseases that were previously difficult to manage such diabetes, chronic pain, and neurodegenerative disorders. However, translation of these novel technologies into clinical practice is often difficult because fibrotic encapsulation and/or rejection impairs device function after body implantation. Ideally, cells of the host tissue should perceive the surface of the implant being similar to the normal extracellular matrix. Here, we developed an innovative approach to provide implant surfaces with adhesive protein micropatterns. The patterns were designed to promote adhesion of fibroblasts and macrophages by simultaneously suppressing fibrogenic activation of both cell types. In a rat model, subcutaneously implanted silicone pads provided with the novel micropatterns caused 6-fold lower formation of inflammatory giant cells compared with clinical grade, uncoated, or collagen-coated silicone implants. We further show that micropatterning of implants resulted in 2-3-fold reduced numbers of pro-fibrotic myofibroblast by inhibiting their mechanical activation. Our novel approach allows controlled cell attachment to implant surfaces, representing a critical advance for enhanced biointegration of implantable medical devices.

Long-term follow-up of cadaveric breast augmentation: what can we learn?

Breast augmentation with cadaveric fat graft has long been available to patients in Eastern European countries, primarily in the Soviet Union and Eastern Germany. Most such procedures were performed from the 1970s to the 1990s. Although only a few case reports have been published, all of which involved complications that appeared several years after the procedure, it appears that, surprisingly, this nonvascularized and incompatible immunologic tissue is relatively well tolerated. We present the case of a 45-year-old Russian woman who underwent breast explantation, due to breast hardness and pain, 15 years after breast augmentation with cadaveric fat grafting. Through genetic studies, we confirmed that the host and the graft were HLA incompatible. Moreover, results of analyses excluded the possibility of an acute or chronic immunologic rejection by the host. We suppose that the early complications that often occur in such cases might result from a nonspecific, inflammatory reaction induced by acute tissue ischemia and necrosis, and the late local complications that occur years later may relate more to chronic inflammation, due to nonvascularized tissue, than to immunologic rejection. Therefore, we propose that different mechanisms may explain how this allogenic fat tissue could have been tolerated by the patient's immune system. We particularly underline the immunomodulatory effect of mesenchymal stem cells, which are abundant in adipose tissues. This characteristic of fat tissue should be investigated further to assess its potential in treating autoimmune diseases or reducing the likelihood of allograft rejections.

Risks and benefits of using an absorbable mesh in one-stage immediate breast reconstruction: a comparative study.

BACKGROUND: Complete implant coverage by pectoralis major muscle in immediate breast reconstruction prevents implant exposure but restricts implant volume, increases the risk of a high-riding implant, and prevents natural ptosis. The authors hypothesized that extension of the subpectoral pocket with Vicryl mesh may produce more satisfactory results. The safety and efficiency of this technique were assessed by comparing complication rates and clinical results of the two reconstruction techniques: with and without mesh. METHODS: The authors reviewed 161 immediate breast reconstructions in 139 patients from 2002 to 2010. A complete submuscular pocket was performed in 46 breasts and a partial submuscular pocket with Vicryl mesh extension was performed in 115 breasts. Complications, surgical revisions rates, implant size, and contralateral breast procedures were compared between the two groups. RESULTS: Early and late surgical revisions were similar between the mesh and nonmesh groups (11.6 percent versus 4.3 percent at 90 days, p = 0.09; and 34.3 percent versus 41.4 percent at 5 years, p = 0.41). There were fewer revisions for implant malposition in the mesh group (8.9 percent versus 21.7 percent, p = 0.05). Patients with mesh could have a larger implant in comparison with those without mesh (329 g versus 284 g, p = 0.01) and had fewer contralateral mastopexies (12 percent versus 30 percent, p = 0.01). CONCLUSIONS: Larger implants and perhaps better control of implant position were possible using the Vicryl mesh extension without increasing complications. Because the mesh technique also recreates a slightly ptotic breast, fewer contralateral mastopexies were needed. The Vicryl mesh extension is a low-cost alternative to biological matrices or tissue expanders. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Nonactivated versus thrombin-activated platelets on wound healing and fibroblast-to-myofibroblast differentiation in vivo and in vitro.

BACKGROUND: Platelet preparations for tissue healing are usually preactivated before application to deliver concentrated growth factors. In this study, the authors investigated the differences between nonactivated and thrombin-activated platelets in wound healing. METHODS: The healing effects (i.e., wound closure, myofibroblast formation, and angiogenesis) of nonactivated and thrombin-activated platelets were compared in experimental wounds in diabetic (db/db) animals. In vitro, fibroblast phenotype and function were tested in response to platelets and activated platelets. No treatment served as a negative control. RESULTS: Wounds treated with platelets reached 90 percent closure after 15 days, faster than activated platelets (26 days), and with higher levels of myofibroblasts and angiogenesis. In vitro, platelets enhanced cell migration and induced two-fold higher myofibroblast differentiation and contraction compared with activated platelets. CONCLUSIONS: Platelets stimulate wound healing more efficiently compared with activated platelets by enhancing fibroblast differentiation and contractile function. Similar levels of growth factors may induce different biological effects when delivered "on demand" rather than in an initial bolus.

[Tracheal replacement grafts: current options]. / Greffes trachéales: options actuelles.

A critical review of publications on tracheal reconstruction is presented. The extent of the resection defect in terms of horizontal circumference or longitudinal extension determines the difficulty of the reconstruction. To allow a valid comparison, a classification of tracheal defects is proposed. The reconstruction materials can be subdivided into synthetic grafts, autografts, allografts, and bioengineering constructs. Reconstruction of tracheal defects greater than half of the tracheal length was not possible until recently. Numerous publications on animal experimental techniques, and rare human case reports show few successful outcomes. During the last five years, new reconstructive options have emerged: autograft of composite flaps mimicking tracheal architecture and bioengineered tracheal constructs.

Locating perforator vessels by dynamic infrared imaging and flow Doppler with no thermal cold challenge.

BACKGROUND: Dynamic Infrared Imaging (DIRI) is a noninvasive technique that precisely analyzes the infrared radiation of any object. We used this technique to locate the dominant perforator vessels in flap surgery in conjunction with conventional Doppler. METHODS: Ten patients scheduled for deep inferior epigastric artery perforator flap and 6 for free-fibular flaps were selected. Perforator vessels were localized in the donor area, using Doppler and DIRI. The ability to locate the dominant perforators was compared between both techniques. RESULTS: DIRI produced a precise map showing the location of the perforators and their area of perfusion at the skin level. Their dominance can be determined by their size. Flow Doppler located the perforators at the aponeurotic level without size and perfusion information. CONCLUSIONS: DIRI produces a skin thermographic map of perforator vessels and their perfusion area. Handheld Doppler locates perforators at the aponeurotic level. Their combination increases safety in the planning of perforator flap surgery.

A facial inflammatory myofibroblastic tumour in a 6-year-old girl: plastic surgery lessons from a rare case.

Inflammatory myofibroblastic tumours (IMT) are rare, challenging lesions with respect to differential diagnosis, biological behaviour and treatment. We reviewed the literature and report a unique case of a large (9 × 8 × 8 cm) IMT in the nasal region of a 6-year-old girl responsible for important facial deformation. Following surgical resection, without any craniofacial reconstruction, the dysmorphism regressed spontaneously with a good result at 2 years of follow-up. To date, this is the largest IMT reported. Surprisingly, after simple excision of the tumour the craniofacial bones and soft tissues regained spontaneously their normal anatomical position only after a few months. The bone plasticity was likely due to the young age of patient and the preservation of periosteum and muscles during the surgical excision. We conclude that a conservative approach may be considered as alternative to reconstructive surgery in particular cases in young subjects.

Superior pedicle breast reduction for hypertrophy with massive ptosis.

Breast hypertrophy, combined with massive ptosis with a suprasternal notch-to-nipple distance of more than 40 cm, remains an endeavour. Different refinements of the initial technique with free nipple grafts have been described to circumvent the problems of nipple underprojection, areolar hypopigmentation and loss of sensibility secondary to nipple grafting, as well as lacking breast projection due to scarce glandular tissue. Techniques relying on nipple areola complex transposition, rather than grafting, have been described with inferior, superomedial and medial pedicles. The aim of this study is to present the results obtained in a series of 10 patients suffering from bilateral breast hypertrophy with massive ptosis, which was defined as a distance >40 cm from the suprasternal notch-to the nipple. All breasts were managed with a superior pedicle and inverted T technique. The mean preoperative suprasternal notch-to-nipple distance was 44 ± 2 cm, and the resection weight ranged from 800 to 2490 g per breast with an average of about 1450 g in this patient population presenting with overweight or obesity. With a mean nipple areola complex (NAC) lift of 20 ± 3 cm, neither nipple nor areola necrosis was observed. One partial epidermolysis of the areola and two cases of delayed wound healing at the trifurcation point of the inverted T were conservatively managed. Only one re-operation was necessary for an important wound dehiscence of the lateral part of the horizontal scar. These results underscore the safety of the superior pedicle technique in cases of massive ptosis with transposition of the NAC of approximately 20 cm, that is, a pedicle length of about 25 cm.

Hypoxia impairs skin myofibroblast differentiation and function.

Ischemic wounds are characterized by oxygen levels lower than that of healthy skin (hypoxia) and poor healing. To better understand the pathophysiology of impaired wound healing, we investigated how switching from high (21%) to low (2%) oxygen levels directly affects cultured skin myofibroblasts, essential cells for the normal wound repair process. Myofibroblast differentiation and function were assessed by quantifying α-smooth muscle actin expression and cell contraction in collagen gels and on wrinkling silicone substrates. Culture for 5 days at 2% oxygen is perceived as hypoxia and significantly reduced myofibroblast differentiation and contraction despite high levels of the profibrotic transforming growth factor-ß1. Analysis of α-smooth muscle actin expression on wrinkling substrates over time showed that reduced myofibroblast contraction preceded α-smooth muscle actin disassembly from stress fibers after switching from 21 to 2% oxygen. These effects were reversible by restoring high oxygen conditions and by applying mechanical stress. We suggest that mechanical challenge is a clinical relevant strategy to improve ischemic and chronic wound healing by supporting myofibroblast formation.

Early detection of flap failure using a new thermographic device.

BACKGROUND: Early recognition of perfusion failure is critical for free flap salvage. However, most of the different methods assessing perfusion have limitations and have not gain widespread acceptance. The aim of this study was to evaluate a novel system, a combination of a highly sensitive infrared camera with dynamic infrared image processing, in an animal flap model. MATERIALS AND METHODS: Flaps based on the inferior superficial epigastric vessels were raised bilaterally in 20 rats. One pedicle artery or vein was ligated and the contralateral side served as unligated control. Thermographic measurements were performed before and after ligation yielding a color map and a temperature recording. The macroscopic evolution of the flap was photographically documented. RESULTS: All vascular occlusions were rapidly detected. In the artery ligated group, the disappearance of the hot spot, corresponding to the pedicle, was observed in absence of macroscopic changes of the flap. In animals undergoing venous ligation, changes in the thermographic image preceded clinical signs of congestion. Temperature recordings between arterial and venous ligation were not significantly different. CONCLUSIONS: Vascular compromise was rapidly and consistently identified prior to appearance of macroscopic changes. This very sensitive system allows for a precise detection of small differences of infrared emission within the flap visualized as changes in the color map with disappearance of the hot spot on the color map. This is independent of absolute temperature values that are influenced by environmental factors. In addition to postoperative monitoring, the set-up may be a promising tool for preoperative planning of perforator flaps.

Erythropoietin protects critically perfused flap tissue.

OBJECTIVE: The objective of this study was to analyze whether erythropoietin (EPO) protects from necrosis of critically perfused musculocutaneous tissue and the mechanisms by which this protection is achieved. BACKGROUND: EPO is the regulator of erythropoiesis and is used to treat patients with anemia of different causes. Recent studies suggest that EPO has also other tissue-protective effects, irrespective of its erythropoietic properties. MATERIAL AND METHODS: C57BL/6-mice were treated with 3 doses of EPO at 500 IU/kg intraperitoneally. EPO was given either before (preconditioning, n = 7), before and after (overlapping treatment, n = 7), or after (treatment, n = 7) surgery. Animals receiving only saline served as controls (CON). Acute persistent ischemia was induced by elevating a randomly perfused flap in the back of the animals. This critically perfused tissue demonstrates an initial microvascular failure of approximately 40%, resulting in approximately 50% tissue necrosis if kept untreated. Repetitive fluorescence microscopy was performed over 10 days, assessing angiogenesis, functional capillary density, inflammatory leukocyte-endothelial cell interaction, apoptotic cell death, and tissue necrosis. Additional molecular tissue analyses included the determination of inducible nitric oxide synthase, erythropoietin receptor (EPO-R), and vascular endothelial growth factor (VEGF). RESULTS: EPO preconditioning did not affect hematocrit and EPO-R expression, but increased inducible nitric oxide synthase in the critically perfused tissue. This correlated with a significant arteriolar dilation, which resulted in a maintained functional capillary density (CON: 0 +/- 0 cm/cm(2); preconditioning: 37 +/- 21 cm/cm(2); overlapping treatment: 72 +/- 26 cm/cm(2); P < 0.05). EPO pretreatment further significantly reduced microvascular leukocyte adhesion and apoptotic cell death. Moreover, EPO pretreatment induced an early VEGF upregulation, which resulted in new capillary network formation (CON: 0 +/- 0 cm/cm(2); preconditioning: 40 +/- 3 cm/cm(2); overlapping treatment: 33 +/- 3 cm/cm(2); P < 0.05). Accordingly, EPO pretreatment significantly reduced tissue necrosis (CON: 48% +/- 2%; preconditioning: 26% +/- 3%; overlapping treatment: 20% +/- 3%; P < 0.05). Of interest, EPO treatment was only able to alleviate ischemia-induced inflammation but could not improve microvascular perfusion and tissue survival. CONCLUSIONS: EPO pretreatment improves survival of critically perfused tissue by nitric oxide -mediated arteriolar dilation, protection of capillary perfusion, and VEGF-initiated new blood vessel formation.

Optimizing the arterialized venous flap.

BACKGROUND: Outcome of arterialized venous flaps is quite varied. The authors' initial experiments showed that a good vascular bed contributes significantly to survival of the flap. In continuation of these experiments, this study aimed to understand the influence of architectural variations on flap outcome. METHODS: Fasciocutaneous flaps were designed on the ears of New Zealand rabbits, and the animals were randomized into four groups having flaps that used the larger anterior marginal vein (1.3 mm) or the smaller central vein (0.6 mm) for arterial inflow, with or without isolation of the flap from its bed with a silicone sheet. Flaps were observed for area of flap survival and vasculature was assessed by microangiography. RESULTS: Using the smaller central vein for arterial inflow (n = 15), arterialized venous flaps had an excellent outcome, with good flap survival in 100 percent of the animals (survival of >85 percent of flap area), and a mean flap survival area of 99.4 +/- 1.6 percent. Even when neovascularization was prevented by isolation of the flaps (n = 14), 92 percent of central vein flaps showed good survival, with a mean flap survival area of 93.3 +/- 7.3 percent, which was significantly better than that of anterior marginal vein flaps (n = 22), which showed good flap survival in only 27 percent of the animals (mean flap survival area, 76.4 +/- 12.1 percent). CONCLUSIONS: Survival of arterialized venous flaps is optimized by using smaller-caliber veins for inflow and reserving larger-caliber veins for outflow. This regulates inflow and avoids high blood pressure, and arterialized venous flaps behave as physiologic flaps do, by not relying on neovascularization for survival.

Mixed arterio-venous insufficiency in random skin flaps in the rat: is the application of medicinal leeches beneficial?

BACKGROUND: Leeches are commonly used in reconstructive surgery for the treatment of venous congestion in flaps. Documented mechanisms of action are (1) injection of the anticoagulant hirudin; (2) active suction of blood; and (3) passive oozing of the bite wound. Even though the benefits of leeches in venous congestion are widely accepted, little is known about their effects in mixed arterio-venous insufficiency. METHODS: Thirty Wistar rats were randomized into three groups (n = 10 each), and 9 x 3 cm ischemic random skin flaps were elevated on the rat dorsum. Group 1 served as controls. In group 2, one leech was applied to the distal part of the flap and in group 3, three leeches were applied, one at a time, at 8 h intervals. Postoperatively, flap survival and perfusion were quantitated by daily planimetry and laser-Doppler imaging. RESULTS: The application of a single leech on postoperative day 7 did not lead to any statistically significant changes in total flap survival or tissue perfusion. Triple leech application, however, caused a significant decrease in flap survival of 6.6% at day 7 (3x leech versus control: 45.8% +/- 8.5% versus 52.4% +/- 8.5%, respectively) (P < 0.01) and a decline in flap perfusion of 13% (3x leech versus control: 71.3% +/- 16.6% versus 84.3% +/- 9.3%, respectively) (P < 0.01). CONCLUSION: The data demonstrate that the application of leeches in the setting of mixed arterio-venous insufficiency can be hazardous to flap viability. Pure venous congestion with an adequate arterial supply remains the only indication for controlled leech application in the clinical setting.

Hypoxic preconditioning increases skin oxygenation and viability but does not alter VEGF expression or vascular density.

Intermittent hypoxia is known to elicit adaptive changes that increase tissue oxygen delivery. We investigated the effects of intermittent hypoxic exposure (IHE) in normal skin (course study) and evaluated whether preoperative IHE-preconditioning alleviates acute ischemic injury in skin flaps (flap study). For 4 weeks, 55 rats were exposed to a daily IHE-session (6 hypoxic cycles, 9% O(2), 6 to 10 min) separated by 3 min of reoxygenation (20.9% O(2)). The time course of intracutaneous PO(2) was measured at weekly intervals. VEGF/VEGF-receptor-mRNA and vascular density were measured in normal skin before and after 1, 2, 3, and 4 weeks of the IHE course (20 rats). In 35 rats, skin flaps were elevated after IHE and similar studies were undertaken in samples from 3 flap areas at postoperative days 0.5, 2, and 4. Additionally, flap survival and cutaneous blood flow were quantitated. In normal skin, PO(2) was initially significantly decreased during the hypoxic cycles (PO(2) 4.1 +/- 1.5 mmHg). After 4 weeks of IHE, PO(2) (34.5 +/- 5.8 mmHg) was maintained even under hypoxic conditions. In flaps, IHE led to a 2.6-fold increase in PO(2), increased flap survival (+ 19.4%, day 7), and blood flow (+ 19.1%, day 10) (p < 0.01). In neither study did IHE-preconditioning increase VEGF/VEGF-receptor-mRNA expression or vascular density. We conclude that (1) IHE induces pronounced hypoxia in the skin, but progressive adaptation occurs within 4 weeks, (2) preoperative IHE-preconditioning leads to significantly higher PO(2), blood flow, and tissue survival in ischemic skin flaps, and (3) the transient hypoxia induced by IHE does not alter expression of VEGF or its receptors nor does it trigger angiogenesis.

Ischemia-induced up-regulation of heme oxygenase-1 protects from apoptotic cell death and tissue necrosis.

BACKGROUND: Tissues are endowed with protective mechanisms to counteract chronic ischemia. Previous studies have demonstrated that endogenous heme oxygenase (HO)-1 may protect parenchymal tissue from inflammation- and reoxygenation-induced injury. Nothing is known, however, on whether endogenous HO-1 also plays a role in chronic ischemia to protect from development of tissue necrosis. The aim of this study is, therefore, to evaluate in vivo whether endogenous HO-1 exerts protection on chronically ischemic musculocutaneous tissue, and whether this protection is mediated by an attenuation of the microcirculatory dysfunction. MATERIALS AND METHODS: In C57BL/6-mice, a chronically ischemic flap was elevated and fixed into a dorsal skinfold chamber. In a second group, tin-protoporphyrin-IX was administrated to competitively block the action of HO-1. Animals without flap elevation served as controls. With the use of intravital fluorescence microscopy, microcirculation, apoptotic cell death, and tissue necrosis were analyzed over a 10-day observation period. The time course of HO-1 expression was determined by Western blotting. RESULTS: Chronic ischemia induced an increase of HO-1 expression, particularly at day 1 and 3. This was associated with arteriolar dilation and hyperperfusion, which was capable of maintaining an adequate capillary perfusion density in the critically perfused central part of the flap, demarcating the distal necrosis. Inhibition of endogenous HO-1 by tin-protoporphyrin-IX completely abrogated arteriolar dilation (44.6 +/- 6.2 microm versus untreated flaps: 71.3 +/- 7.3 microm; P < 0.05) and hyperperfusion (3.13 +/- 1.29 nL/s versus 8.55 +/- 3.56 nL/s; P < 0.05). This resulted in a dramatic decrease of functional capillary density (16 +/- 16 cm/cm(2)versus 84 +/- 31 cm/cm(2); P < 0.05) and a significant increase of apoptotic cell death (585 +/- 51 cells/mm(2)versus 365 +/- 53 cells/mm(2); P < 0.05), and tissue necrosis (73% +/- 5% versus 51% +/- 5%; P < 0.001). CONCLUSION: Thus, our results suggest that chronic ischemia-induced endogenous HO-1 protects ischemically endangered tissue, probably by the vasodilatory action of the HO-1-associated carbon monoxide.

Persistent ischemia impairs myofibroblast development in wound granulation tissue: a new model of delayed wound healing.

We describe a new animal model designed to assess the impact of ischemia on wound healing. Eight patterns of arterial lesion in the limb were first tested in 24 Wistar rats. Resection of the external iliac artery down to the femoral artery at the level of the knee was chosen as the reference model and performed on the left limb of 45 rats; the right limb was used as the control. Skin wounds measuring 1.2 x 0.8 cm were created on both feet. Ischemia was assessed by blood flow measurement, which decreases dramatically in the ischemic limb. A significant delay in wound closure with a decrease in wound contraction was observed in the ischemic limb. Myofibroblast quantification showed a significant delay in appearance as well as a decrease in the number of these cells in the ischemic wound. Vascular endothelial growth factor-A appearance and evolution were qualitatively similar in both situations. However, collagen type I mRNA was markedly decreased in ischemic granulation tissue 10 days after wounding. These findings suggest that decreased wound contraction plays an important role in delayed ischemic wound healing, probably due to reduced myofibroblast development and activity.

[Skin-sparing mastectomy and immediate breast reconstruction]. / Mastectomie avec préservation cutanée et reconstruction immédiate.

Skin-sparing mastectomy is a new surgical approach that allows a mastectomy while preserving the natural envelope of the breast. Skin-sparing mastectomy followed by immediate reconstruction can be used for prophylaxis for high- risk patients or BRCA carriers. It represents an effective treatment option for patients with extensive DCIS or early invasive breast cancer, but is contraindicated for inflammatory breast cancer and extensive skin involvement by the tumor. Skin-sparing mastectomy had similar surgical outcomes compared to non- skin- sparing mastectomy, but skin flap ischemia and necrosis is more common and is associated with a range of risk factors, including smoking. Skin-sparing mastectomy seems to be an oncologically safe technique and does not increase in particular the risk of local, regional or systemic recurrences. It facilitates immediate breast reconstruction using implants or myocutaneous flaps, resulting in excellent cosmesis and high level of patient satisfaction. This article reviews the published data on skin-sparing mastectomy and immediate reconstruction and aim to establish its current role in clinical practice, as there is a lack of prospective data.