Safi Kang, MD.
(Korean Society of Korean Cosmetic Surgery and Medicine)
· 国外来稿 ·
Breast augmentation using autologous fat transplantation
Safi Kang, MD.
(Korean Society of Korean Cosmetic Surgery and Medicine)
Recently, cosmetic surgery is getting well known and patients not only have interest in face surgery but their interest in body surgery is growing as well. Whether it is Asians or Westerners, breast surgery is one of the most famous fields in cosmetic surgery. In particular, Asians have relatively smaller breast size compared to the Westerners, hence breast augmentation procedures are conducted more frequent than breast reduction procedures. The main materials for breast augmentation are artificial implants, artificial fillers and autologous tissues (fat, muscle, etc.). Currently, the material that is most commonly used in breast augmentation procedures is the artificial silicone implant. However, autologous fat does not have foreign body reaction, can be obtained easily, costs economically, and additional benefits can be expected for body contouring, hence interest and use of this procedure are increasing recently. Be same with facial fat transplantation, controversial factors for breast augmentation that uses autologous fat are the survival rate and longevity. Because the fat′s survival and longevity directly affect the success of the results.
2.1 Extraction and separation step
Selection of donor site for breast fat transfer is not different from that for facial fat transfer. However, as large amount of fat is required, we have to select a region that can get the sufficient amount of fat. Hudson DA et al. reported that thigh has more lipogenic activity[1], while Rohrich R et al. reported that there is no difference in adipocyte longevity of different body parts[2], interestingly, Schipper BM et al. reported that the resistance of the aptosis of the adipose-derived stem cells in the fat layer above of abdominal scarpa′s fascia is bigger than the deep layer cells below the fascia, so it is a better donor site[3]. The donor site for fat transfer is still in controversial. Author prefers to use the abdomen and femoral region. But, unlike the Westerners, Asians are more concerned of how much amount of fat can be harvested without causing damage to cells, compared to choole which part of the body as the donor site.
In terms of negative pressure of suction to reduce the damage to adipocytes, pressure inside the syringe of Coleman has been reported as the safest. There are many controversies on the reports of the diameter of the cannula for suction, in general, it is acceptable if the diameter is in between 2.5 mm to 4 mm. There is also debate on exposure to air and basically centrifugation is based on the principle of no contact with air.
Centrifugation for breast fat transfer has been adapted quite differently from that of facial fat transfer. Although the standard Coleman technique of fat transplantation preparation requires 1200 r/min centrifugation, recently there are many experiences with breast fat transplantation that gradually moved to a low 15 r/min centrifugation method. The original 1200 r/min technique is well adapted to small-volume grafts in the face but is not well suited for megavolume grafts to the breast[4].
Daniel Del Vecchio et al. harvested fat using standard machine aspirator canister. After discarding unwanted crystalloid, fat was transferred to 60 ml syringes, which were capped and placed on a sterile, hand-crank centrifuge. Spinning at 30 to 40 r/min, additional crystalloid and blood were separated from the fat in 3 min. The rationale for low g-force spinning is to efficiently remove unwanted blood and crystalloid, with less potential cell trauma than is seen at 1300 r/min, when motorized centrifuges are used[5].
After centrifugation, the uppermost oil layer and the lowermost layer consisted of blood, tissue fluid, and tumescent solution should be removed because injection of the oil and tissue fluid into the recipient site can increase the incidence of inflammation.
2.2 Phase of fat transplantation
Research on the survival rate of grafted adipocytes (2002) showed that adipocytes with the size of 25 mm3reach the central part and angiogenesis appear after 3 d and angiogenesis is relatively slow in the central part compared to the boundary area[6]. With the basis of these results, when large amount of fat is injected, longevity at border area can be maintained but ischemia occurs nearer to the core that leads to necrosis and results in scar tissue, which eventually felt hard or lumpiness[7]. However, the calcification of lump from fat transplantation can easily be differentiated from calcification caused by cancer through CT scan.
To prevent these complications, the most important point is the thickness of the injected fat. It is all right for the fat′s diameter to be up to 2 mm, hence the inner diameter of the cannula should not be bigger than 2 mm.
Because the purpose is to enhance the size of the breasts in the case of breast augmentation, large amount of fat is injected in most of the cases compared to facial fat transplantation. It is inevitable for high rate of necrosis of the grafted fat as blood circulation of tissues in breast is relatively poor[8]. In this respect, there is a report that mentioned that it is better to graft the fat into pectoralis major muscle which has better blood circulation[9].
Currently, popular fat placements for breast augmentation are the subcutaneous fat layer, on, around, and under the mammary glands, and also on and into the pectoralis major muscle.
The volume of fat injection is also a very important influencing factor on the survival rate of the grafted fat. As mentioned above, if the distance is 2 mm between the grafted fat and the surrounding tissues should be maintained, the amount of grafted fat also have to be diversified depending on the preoperative original volume of each patient′s breast. It is because that the volume of the recipient is greater, which means the higher capacity of diffusion and angiogenesis in the recipient. The more amount fat injection into the patient who has less soft tissue of her or his breast, the more risk of complication such as oil cyst, necrosis, calcification, and lump.
According to many reports, the fat volume for breast augmentation for Westerners is much more than Asians, even though the Westerners body has larger physique than Asian. In the beginning of breast fat transplantation in Korea, average of 250 ml fats had been used for one side breast augmentation. In recent years, 100 to 150 ml volume of centrifuged fat for one side of the breasts is commonly used. This is because there is higher probability of complications when fat is grafted more than this volume.
However, there a research that reported, even massage was carried out after small amount of fat transplantation (60 ml), clustered microcalcifications were still found postoperatively. To reduce the complications of breast fat transplantation, it was stated that they did not graft more than 60 ml of fat per operation per side and that massage was necessary. The main idea was that it was easier for the adipocytes to live as isolated cells than in bulges[10]. They suggested that small amount of fat injection and massage cannot prevent calcifications.
There is an important pre-condition that may be missed. It was whether the surgeon could maintain the thickness of the grafted fat the same, and maintain the 2 mm distance of gap between the grafted fat and the fat tissues. Besides, even if fat transplantation was performed ideally, the massage was performed but it can causes damage to the grafted fat and there is a high possibility that the grafted adipocytes will bump into each other and form lump, hence it is not an appropriate method. In order to increase volume to obtain a natural result, if the fat is evenly injected into appropriate regions and layers with fine shape of fat for the prevention of lump, and it is not necessary to perform massage.
To inject the fat, blunt infiltration cannulas were used to place the fat through 2 mm incisions positioned to allow placement from at least two directions into each area. A blunt cannula can reduce the chance of intravascular injection into the retromammary space[11].
Adipocytes are highly resistant to the forces of positive and negative pressure alone. However, they are remarkably susceptible to the effects of shear stress, which is proportional to flow rate. Among other things, slow injections (0.5 to 1.0 ml/s) demonstrated a 38 percent improvement in fat transplantation survival over fast injections (3 to 5 ml/s). Based on these data, the use of high suction pressures for added efficiency and slow injections between 0.5 and 1.0 ml/s for optimum fat transplantation survival were recommended. Special consideration should be made for the variety of factors that affect shear stress[12].
2.3 Phase of fat survival
In order to increase the survival rate of grafted fat at the phase of fat survival, many active researches are being carried out now on PRP, CAL, and Brava. I will explain briefly on these researches.
To overcome the problems associated with autologous fat transfer, a novel strategy known as cell-assisted lipotransfer (CAL) is used. The progenitors, currently known as adipose-derived stem/stromal cells (ADSCs), are expected to become a valuable tool in a wide range of cell-based therapies. Aspirated fat has approximately half the number of ADSCs found in excised whole fat. With the CAL strategy, autologous ADSCs are used to enhance angiogenesis, to improve the survival rate of grafts, and to reduce postoperative atrophy. In CAL, half the volume of the aspirated fat is processed for isolation of the stromal vascular fraction (SVF) containing ADSCs[13].
On the other hand, it is demonstrated that breast fat transplantation enriched with platelet-rich plasma at 10% does not enhance fat transplantation take compared with fat transplantation (according to Coleman) alone. The lack of clinical evidence on the efficacy of platelet-rich plasma in enhancing fat transplantation take when compared with the well-known Coleman fat transplantation suggests that further research and prospective clinical studies are needed to understand the role of platelet-rich plasma, if any, in fat transplantation[14].
Additionally, Brava breast expansion enables the transfer of large volumes of fat in a single session safely and effectively while ensuring a very high survival rate, with augmentation volumes comparable to implants and the added benefit of a more natural appearance and feel[14].
Brava uses a vacuum pump to expand the skin and stromal/vascular scaffold, so that many microribbons of fat can be diffusely injected without coalescence or significantly increased interstitial fluid pressure[15]Patient compliance with Brava wear is essential; They must triple their volume to obtain a final augmentation that is double the original volume[16].
(1) Application of PRP
In order for the grated fat to survive, the most important condition is contact with new blood vessels. To achieve this, generation of new blood vessels (angiogenesis) can provide nutrients for grafted fat and is important for the mutual benefit between vascular endothelial cells and adipocytes[17]. The most effective way is using a growth factor that can promote angiogenesis. However, clinically there is no single formulation that can be administered to a patient to promote angiogenesis. However, the most important and powerful growth factors are vascular endothelial growth factor and angiopoietin-1[18].
These reasons become the theoretical background of platelet-rich plasma (PRP) application in fat transplantation. This is because activated PRP has protein growth factors (PDGF-αβ, PDGF-β, TGF-1,TGF-β2, VEGF, EGF, and IGF-1). Still there are debates over the effect of injecting PRP combination to increase graft take rate during fat plantation. In vitro researches report, injecting PRP combination is effective, whereas in vivo researches report yet question the effect.
In terms of clinical report, Cervelli V et al[19]reported that when PRP-combined fat was injected into facial concavity, there were enhanced survival rate and volume maintenance compared to fat-only injection. Nevertheless, Salgarello M et al[20]reported that there were no effects in breast augmentation.
It was reported that surgery result differs depending on the ratio of injected fat and PRP. In general, the combination ratios of fat and PRP in various researches were 9∶1 (10%), 4∶1(20%)[20-21]and 2∶1 (33%)[14]. Cases with ratios of 9∶1 and 4∶1 were reported to have no effect, whereas cases with 2∶1 ratio were reported to be effective, suggesting that this concentration is appropriate[16]. Although no solid proof, in my clinical experience 1∶9 ratios can improve survival rate. Use of PRP after grafting showed positive findings as it can reduce swollen and have the effect of speedy recovery.
It is possible that using PRP greatly affects survival in fat transplantation. Yet there are no clear results or proofs to confirm the effects of the survival rate increase in human body researches. However, there are possibilities that PRP positively affects fat transplantation as summarized below.
First of all, when transplanted to body, fat itself constitutes to dilutional hypotonic environment in recipient bed even though it was suctioned by isotonic Klein′s solution during harvest. It is because transplanted fat and combined Klein solution dilute interstitial protein concentration[22]in recipient bed tissue; thus, colloid osmotic pressure declines. It causes gross edema and damages adipocytes, resulting in shrinkage of transplanted fat. However, PRP contains albumin, globulin, fibrinogen and etc. To prevent osmotic pressure decline and, as a result, can provide appropriate environment for fat to graft[23].
Second, prior to vessel supply, transplanted adipocytes acquire nutrients by diffusion from plasma in about 48 h after transplantation.Third, through the effects of various activators including growth factors secreted from activated platelets, healing process and angiogenesis in recipient bed will be promoted.
Fourth, some reports from practical laboratory researches[24]suggest that PRP positively affect angiogenesis or ADSC proliferation. Of course, researches of PRP effects were mostly about vascular endothelium[25], bone marrow stromal cell[26], and umbilical vein endothelium[27]. Some also reported that there is a positive effect in 5% PRP concentration, while the proliferation decreased in 20% PRP concentration due to thrombospondin-1′s oversecretion[23]. According to the results above, the potentiality of PRP for fat transplantation is not skeptical. But, adipose tissue undergoes more complicated processes such as basement membrane breakdown during angiogenesis, vasculogenesis, angiogenesis, angiogenic remodeling, vessel stabilization, vascular permeability, etc. Therefore, there is a huge possibility that the effect may be restricted.Fifth, the body research results to prove PRP′s efficiency in fat transplantation are not satisfactory yet. But, the recent body research results of Cervelli et al. are evaluated to show PRP′s possibility[28].
However, the larger the volume of fat, the more blood volume has to be used, hence, it is important to pay attention to this limitation when using PRP.
(2) Application of CAL
Recently, CAL method that is related to the function of stem cells on angiogenesis is being researched actively. The factors related to CAL are explained as below.First, ADSCs are involved in tissue regeneration by self-produced differentiation into adipocytes[29].Second, ADSCs are reported to have possibility of differentiating into vascular endothelium or pericytes[30]. Third, hypoxia condition in the acute phase after fat transplantation may release angiogenic soluble factors such as VEGF and HGF, accelerating[31].Fourth, surgical injury accompanying the transplantation and subsequent hypoxia condition and wound healing process appear to trigger ADSCs differentiation into adipocytes, vascular endothelial cells, and mural cells[32]. Fifth, ADSCs are reported to increase fat survival rate by preventing fibrosis and fat necrosis through differentiating into endothelium when transplanted together with adipocytes[33]. Sixth, according to more detailed result recently, ADSCs are reported to differentiate into adipocytes and also maintain the adipocytes survival by preventing apoptosis by expressing VEFG and IGF-1 which are angiogenic growth factors[34].Recently, in comparison with CAL method, research that used water jet by Hilkka H. Peltoniemi, et al. is very interesting. They reported a high survival rate after WAL and cell enrichment in the presented patients, but not better than in patients purely treated with water jet-assisted liposuction (WAL), without stem cell enrichment. WAL alone is faster (90~150 min less), cheaper (cost of consumables for each patient), theoretically safer (lower risk of contamination) and offers at least the same take rate. We do not see any advantage in stem cell enrichment by the Celution system in cosmetic fat transplantation to the breast[35].
(3) Application of BRAVA
In 1999, an external breast tissue expander was introduced as a nonsurgical alternative to breast augmentation. The Brava device (Brava LLC, Miami, Fla.) consists of two semirigid polyurethane domes that are placed around the breasts and that interface with the skin through silicone gel-filled donut bladders. These bladder rims serve to maintain an airtight seal and to dissipate pressure and shear forces. A small, battery-operated, microchip controlled minipump maintains 20 mm/Hg of negative pressure inside the domes. This vacuum effectively exerts an isotropic distractive force to the breast. The entire system is contained within fabric and worn like a brassiere[36].
Recently, in order to increase the survival rate of grafted fat, the most effective factor is the pressure on the grafted fat. There are many active researches on breast reconstruction and augmentation surgery using fat transplantation lately. Several interesting reports are shown below. Firstly, preoperative Brava use has effected on the patient who had mastectomy with or without irradiation therapy as follows.
In non-irradiated total mastectomy cases, preoperative wearing of the Brava device resulted in good extension of the skin envelope and significant increase of the recipient space in the area where the residual tissue continued to be soft. Mechanical stimuli have been suggested to directly stimulate cell proliferation of the recipient bed[37]. These changes lead to decreased interstitial pressure and increased graft volumes per session. In addition, simultaneous induction of neoangiogenesis can also contribute to improved outcomes after engraftment. The Brava device was particularly effective after skin and nipple-sparing mastectomy[38].
In contrast, in irradiated breast conserving surgery cases, there was barely any skin extension; therefore, improvement of the asymmetric nipple position and breast shape was very difficult extremely adverse effect on the skin and subcutaneous tissue, resulting in the limited efficacy of preoperative Brava use. Postoperative Brava use was expected to result in increased local blood circulation in the recipient bed, which would be advantageous for the engraftment.
Secondly, it has been known that postoperative Brava use is helpful to improve the survival rate of fat transplantation as follows.
External negative pressure exerts an obvious increase in oxygen partial pressure, indicating a rapid increase in blood flow in the subcutaneous adipose tissue. This phenomenon occurs following postoperative Brava use clinically and is effective in promoting engraftment.
Generally, mature adipocytes have the highest oxygen partial pressure in the body (approximately 50 mmHg) and are very vulnerable to a low-oxygen state[39]. In ischemic environments, many adipocytes tend to become necrotic or apoptotic within 3 days after transplantation. Therefore, the Brava device should be used as early as possible after surgery. Eto et al. reported that after grafting, replacement of degenerated fat began on postoperative days 5 through 7, and regenerative adipogenic changes started on postoperative 14 d. Therefore, a 2 weeks use of the Brava device, after grafting, should be theoretically adequate[40].
Therefore, fat transplantation may be useful only in irradiated cases where there is little to no skin deficiency and the deformity is mild. In addition, the theoretical risk of cancer and associated cancer screening requirements are controversial, particularly in breast-conserving surgery cases, because the mammary glands remain in situ and patients are believed to be prone to cancer recurrence. Therefore, in the management of irradiated breast-conserving surgery cases with severe breast deformities, it is suggested that carefully considering the use of not only the Brava device but also fat transplantation.
2.4 Environmental factors
(1) Movement and pressure
Before and after fat transplantation, the main environmental factors affecting survival rate of grafted fat include movement and pressure on adipocytes. After grafting, if there are many body movements, chances of contact of grafted fat and new blood vessels will be reduced and damage to mature adipocytes can be increased[41]. Therefore, should pay attention to wearing fixing underwear-prevent movement, posture during sleep-prevent pressure, and avoid violent exercise after fat transplantation.
It tends to touch and massage when the patient thinks the infiltrated area is over-injected. Warn the patients not to touch or pressure on the infiltrated area by themselves or others after the procedure. Recommend to sleep in a supine position until 3 months after the procedure. Taking shower is fine, but restrain from going to sauna at least for 1 month.
(2) Weight control
Turn over time of original fat in body is generally 2 years and one of transferred fat is 2 to 3 months. It is because of transient ischemia of transferred fat. In my opinion, it is better to keep weight at least 3 months if stem cell is used, or 6 months if stem cell is not used.
(3) Alcohol and Smoking
Bad impacts of smoking and drinking alcohol on fat transfer and sedation anesthesia have to be explained to patients clearly.Also, bad impacts of smoking and drinking alcohol on fat transfer and general anesthesia must be clearly explained as well. Restrict uptake of alcohol at least 1 to 2 weeks before and up to 2 weeks after the operation. It takes about 48 h to completely bio-degrade alcohol on average, but there are a great deal of individual variations reaching thrice or more. Thus, make sure not to drink at least 3 days before the operation.
Especially, smoking can negatively affect sedation anesthesia by reducing vital capacity and increasing secretion. It also leads to increase wound inflammation and delay recovery due to decreased tissue oxygen tension.
Heretofore, abstaining smoking for 4~8 weeks before the operation was known to reduce the occurrence of postoperative complications. However, recently, Clara K. Chow et al. insisted that stop smoking during the period is meaningless. However, they argued that at least 8 weeks of abstaining is needed to show same complication occurrence rate with that of non-smokers[42]. Especially, as respects the concerns of bleeding or anesthesia, patient must quit smoking at least 12 hours before the operation. Also, remind the patient about the possibility of lower survival rate due to smoking and suggest to quit or to reduce smoking at least 1 month to 3 months after the operation to alleviate the problem.
As mentioned above, I have described various factors that affects survival rate and longevity for grafted fat from many researches and a little from my humble experiences.
I focused mainly on diffusion/angiogenesis theory of donor site of adipocytes and overcrowding or excessive interstitial pressure in the recipient. This is because until now researches and clinical practices have always been focused in this regard. There are two hypotheses on survival of grafted fat that coexist, host replacement hypothesis and survival hypothesis, where survival hypothesis receive more spotlights between these two hypotheses. However, there is another new hypothesis that has been introduced lately, scaffold or matrix theory which is rooted in Peer′s host replacement theory. This is comprehensive and progressive in describing reaction of recipient after grafting. This hypothesis lies somewhere between the two above opposing theories: that an element of adult adipocyte survival occurs by diffusion angiogenesis and those cells that do not survive form a biological scaffold for macrophage and induction of angiogenesis and stem cell-mediated adipogenesis. Therefore, this can be described as tandem theory which is comprehensive and progressive in describing reaction of recipient after grafting.[5]Cytokine induced cell-cell signaling between living and dying, and between donor and recipient cells, is also thought to play a role in this process[43].
In a research on factors affecting survival rate at different recipient sites, they suggested that in small-volume fat transplantation, diffusion may play a more significant role; in large-volume grafting, more cells may not survive and the scaffold effect may play a relatively greater role. They also emphasized that further clinical and basic science work will clarify the various weights of these two theories and how they might vary in different recipient sites. This new hypothesis is expected to be of significant help in understanding the difference between the process and results of small volume of fat transplantation for facial fat transplantation and large volume of fat transplantation for breast augmentation.
A significant difference of fat transplantation for breast augmentation from the characteristics of facial fat transplantation is the large volume of fat used for breast augmentation and the recipient is not face. So far, there is still no definite and concrete procedure that is very reliable for fat transplantation for breast augmentation. Breast fat transplantation is being implemented following the relatively successful results of facial fat transplantation. Currently, many researches are being conducted with various attempts to find out the optimal method of breast fat transplantation.
Soon, we can expect to see safe and effective breast fat transplantation to be performed actively and we shall give tribute and encouragement to medical scientists and doctors who are carrying out researches on this aspect.
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《中国美容整形外科杂志》编委
王珍祥,男,1966年出生,博士,副教授、副主任医师。第三军医大学西南医院整形美容外科医院的创建者之一,现为第三军医大学第一附属医院整形外科副主任。2009年到美国德州大学MD ANDERSON癌症研究所、REGENETECH等机构研修。 兼任:西南五省一市烧伤整形学会副主委、中国微循环学会微循环与血液治疗专委会常委、泛亚洲地区面部整形与重建外科学会理事、中国医师协会医学美学与美容分会委员、中国医师协会乳房整形美容亚专委会常委、中华医学会美学与美容分会委员、《中国美容整形外科杂志》编委。在统计源期刊发表论著30篇,参编专著3部。主持国家自然科学基金面上项目2项,重庆市科学基金3项。获军队医疗成果二等奖1项、重庆市科技进步二等奖1项。
从事整形美容专业28年,主要研究方向为难愈性创面修复、病理性瘢痕的临床治疗与基础研究、周围神经损伤与再生的实验研究。长期工作在临床一线,对美容整形的各项手术都很擅长,尤其是各种复杂烧创伤畸形功能恢复、显微外科及美容项目微创手术等。临床经验丰富。独立完成各项复杂疑难的临床治疗,并指导主治医师、住院医师、进修医师、研究生开展临床工作。先后成功完成了英雄梁强、刘咸丰等的治疗康复,成功完成巨大神经纤维瘤手术的重庆卫视现场直播。独立完成头皮撕脱伤的显微外科修复、垫江被强奸活埋1周少女的创伤救治与整形,取得了意想不到的治疗效果,极大减轻患者的痛苦。由于这些病例治疗效果突出,得以在中央电视台2、10频道,重庆电视台等专题报道。在无创抗衰老方面造诣极深,微创除皱抗衰老治疗病例超过5000例,效果佳,国内外患者均评价满意。
李朝阳,男,1972年出生,主任医师,硕士研究生,中国共产党党员。现就职于新疆自治区人民医院整形科。1996年毕业于新疆医科大学,2007年毕业于新疆医科大学研究生院(专业:整形外科)。2001年10月在江苏无锡手外科医院参加手外科显微外科皮瓣学习班。2011年10月至2012年1月在上海市第九人民医院进修。兼任新疆医学会医学美学与美容学分会常委兼秘书、新疆医学会整形外科分会常委兼秘书、《中国美容整形外科杂志》编委。发表各类学术论文10余篇,参与省级(自治区)课题研究1项。
专业特长:⑴在美容方面:能够独立完成重睑、隆鼻术、睑袋整形术、全面部除皱术、隆乳术、巨乳整形术、腹壁去脂整形术、吸脂术、颧骨、下颌角肥大整形及各种美容手术失败后的整形。⑵在整形方面:能够完成各种先天性外伤性烧伤后畸形的整形,如唇、腭裂、歪鼻、斜颈、并指、会阴部整形、基底细胞癌、鳞癌、神经纤维瘤、斑痣以及各种烧伤后瘢痕畸形的整形,各种耳畸形整形、上睑下垂、招风耳、驼峰鼻、文身整形及全耳郭、全鼻再造等,能完成局部皮瓣、带蒂皮瓣及吻合血管、神经的游离皮瓣,能够完成断肢(指)再植手术及各种急诊手外伤的修复整形。