Transplantation in Breast Reconstruction

Jonathan L. Kaplan, M.D., M.P.H.,1 and
Robert J. Allen, M.D., F.A.C.S.2

ABSTRACT
The field of plastic surgery has always dealt with the issue of molding tissue and tissue transfer. For this reason and others, the fact that plastic surgery was the historical forerunner of transplant surgery is no surprise. This evolution was demonstrated very clearly in 1954. This was the year that Dr. Joseph E. Murray and a team of surgeons in Boston performed the first successful kidney transplant between identical twins. The transformation of this one aspect of plastic surgery into the field of transplant surgery has continued to evolve ever since. Kidney transplants between unrelated patients are now commonplace in many medical centers. The practice of transplantation has come to include several other organs and complex tissues such as the pancreas, liver, and hand. Now, most recently, tissue has been transferred from one identical twin to the other for the purpose of breast reconstruction. For the first time ever documented, a deep inferior epigastric perforator flap and a superficial inferior epigastric artery flap were transplanted from one identical twin to another in two separate cases for the purpose of breast reconstruction. The following article briefly discusses a contemporary history of transplantation and provides these two case reports of this seminal procedure between identical sisters.

KEYWORDS
Autogenous breast reconstruction, transplantation, identical twin transplants, perforator artery flap Plastic surgery is primarily concerned with restoring form and function as a result of congenital anomaly, trauma, or disease. To this end, plastic surgeons have used varying techniques to accomplish the ultimate goal of restoring a sense of normalcy and function to the patient. One major tool in their armamentarium is the transferring of tissue to repair a defect. The ability “to mold” defects into a more pleasing esthetic state is often based on the transfer or transplantation of tissue from one region to another. Thus, plastic surgery is and always has been associated with the field of transplanta- tion. This point was well demonstrated in the 20th century when Joseph E. Murray,M.D., a renowned plastic surgeon, and his team performed the first successful kidney transplant between identical twins in 1954.1 A total of 30 transplants had been performed by 1976.2

HISTORICAL REVIEW
In 1954, Dr.Murray performed the first successful kidney transplant between identical twins. The case involved a 24-year-old male with an identical twin brother. The afflicted brother presented with edema and hypertension, 3+ proteinuria, and a greatly decreased hemoglobin and hematocrit. After several admissions and conservative treatment, the patient agreed to a more aggressive treatment plan. On December 23, 1954, a kidney was transplanted from his twin brother. At the initial operation, his native kidneys were left in place. However, the patient’s hypertension persisted, and this prompted his surgeons to reoperate and perform a bilateral nephrectomy. This accomplished two things. First, it cured the patient’s hypertension and, second, it allowed for pathological examination of his native kidneys. The path report revealed that the patient had diffuse advance chronic glomerulonephritis.1 Postoperatively, the donor and recipient did well and lived several more years. This advancement was so important in the medical community that the Nobel Committee in Helsinki felt that Dr. Murray was worthy of the Nobel Prize in Medicine in 1990. Since Dr.Murray’s groundbreaking research, transplantation has been used for organs other than the kidney. Examples of tissue transplantation between identical twins have followed in the case of pancreatic transplants,3 full-thickness skin grafts,4 scalp transfers,5–7 prepuce,8 and bladder mucosal9 transplants in hypospadias repair and bone marrow transplants for hematologic neoplasia.10–14 The precedent set by previous free tissue transfers between identical twins has led to the procedure described subsequently. The following case reports describe the first successful transplants for breast reconstruction between humans.

BACKGROUND
The paraumbilical perforator flap was first described by Koshima and Soeda15 in 1989. This was followed by the use of perforator flaps in breast reconstruction in 1992.16 In using a flap from the lower abdomen based on one or more of the paraumbilical perforators, the surgeon can transfer a well-vascularized flap consisting of fat and skin alone to any recipient vessels elsewhere on the body. The major advantage includes the preservation of the rectus abdominis muscle and therefore the avoidance of complications such as hernia, muscle weakness, reduced range of motion, and increased postoperative pain.17,18 Another recently discovered advantage in using perforator flaps rather than the transverse rectus abdominis myocutaneous (TRAM) flap is the reduced operative time as well as hospital stay and the lower cost of the perforator flap procedure.19

CASE REPORT 1
The two patients involved in the first transplant procedure for breast reconstruction were 46-yearold twin sisters. One sister, the recipient, had a right mastectomy in 1998 for stage II breast cancer. She underwent tissue expansion and implant reconstruction in 1998 and 1999. The capsule around the implant became infected after undergoing postoperative radiation therapy. The patient then requested autogenous reconstruction after explantation of the silicone implant. However, the patient was nulliparous and an avid runner. Therefore, the usual excess abdominal tissue for a paraumbilical flap or excess buttock tissue for a gluteal artery perforator flap was unavailable to perform breast reconstruction. Fortunately, the patient had an identical multiparous twin sister who offered her excess abdominal skin and fat as a flap to be transplanted to her sister (Fig. 1). Before proceeding, testing was done on both patients to ensure that they were indeed monozygotic twins, and therefore the recipient would not require immunosuppressive therapy.20 When performing transplants between nontwin donor and recipients, human leukocyte antigen (HLA) testing is performed to find the closest match. Once a close match is found, the recipient can often survive with a transplanted organ while on immunosuppressive therapy. In the case of differentiating mono- versus dizygosity, HLA typing is not specific enough. In fact, identical HLA serotypes can be found in 25% of normal (nontwin) siblings.21

Therefore, DNA “fingerprint” analysis with the restriction fragment length polymorphism (RFLP) technique was used to determine zygosity.22 Several DNA tests were performed on the twin sisters using the RFLP technique to determine their monozygosity to the highest statistical degree. They were found to be monozygotic, or identical, twin sisters. On February 29th, 2000, at Memorial Medical Center in New Orleans, both sisters were taken to separate operating rooms at the same time. Two surgeons began harvesting the flap on the donor sister while two other surgeons began preparing the recipient internal mammary vessels on the recipient sister. A horizontal ellipse measuring 36 _ 11 cm was incised down to the abdominal muscle wall fascia on the donor sister. The flap was elevated from lateral to medial until the lateral row of perforating vessels was encountered. The surgeons selected the lateral row perforators of the left deep inferior epigastric vessels for flap perfusion (Fig. 2). The perforators were followed through the anterior rectus sheath, through the rectus abdominis muscle, and into the deep inferior epigastric vessels. The anterior rectus sheath was opened longitudinally. No muscle or fascia was harvested with flap elevation.

Pure sensory nerves were dissected several centimeters for coaptation to make this a sensate flap with the transfer. The island of skin and fat only was raised with its corresponding left deep inferior epigastric artery and vein. The ante- rior rectus sheath of the donor site was reapproximated without tension. The skin was then closed in a standard abdominoplasty closure to provide the donor twin a “tummy tuck.” The flap was then taken to the adjacent operating room where the recipient vessels and the fourth intercostal nerve of the sister had been prepared. A skin incision was made excising the previous mastectomy scar. Skin flaps were elevated to form a pocket for the breast transplant flap. The fourth rib cartilage was identified and removed. Underneath the perichondrium, the internal mammary vessels were identified and further isolated from surrounding connective tissue. The flap from the donor sister was brought into the operative field. Using an operative microscope and 9–0 nylon sutures, the internal mammary vein and artery were anastomosed to the deep inferior epigastric artery and vein. There was excellent flow as determined by good color and capillary refill of the flap. A 1-mm Doppler probe was attached to the anastomosed vein, which demonstrated good venous outflow as well. The fourth intercostal nerve was coapted to the sensory nerve of the deep inferior epigastric perforator (DIEP) flap to make this a sensate flap. The breast flap was contoured and inset with a final weight of 505 g
(Fig. 3).

The recipient sister spent the first night in the surgical intensive care unit for flap monitoring. Thereafter, she was transferred to the floor where her sister was recovering from her abdominoplasty. More that 1 year after the operation, both patients are doing well. The recipient sister’s flap is viable and without signs of rejection, as expected. The donor sister’s abdominoplasty healed without any complications.

CASE REPORT 2
On September 5th, 2001, a second pair of twins underwent a transplant procedure for breast reconstruction. The recipient sister had previously undergone a left modified radical mastectomy for breast cancer, which was followed by chemotherapy and radiation. Now that her radiation therapy was concluded, she was interested in autogenous breast reconstruction. Unfortunately, she had an elective abdominoplasty several years previously and, of course, no longer had enough skin and fat or dependable peforators to supply a DIEP or superficial inferior epigastric artery (SIEA) flap. However, she did have a twin sister that had adequate abdominal tissue for breast reconstruction (Fig. 4). Therefore, after determining monozygosity via the RFLP technique described previously, both patients were taken to separate operating rooms concurrently. The donor sister’s abdomen was prepped and draped and an incision made. Meticulous dissection was performed inferolaterally and a sizeable artery and vein of the superficial system were discovered. Therefore, the SIEA and its vena comitantes were dissected bilaterally to the common femoral artery. The superficial system on the right appeared to be larger than the left and was thus chosen as the pedicle to perfuse the flap.While elevating the flap from lateral to medial on both sides, the lateral and medial row of deep inferior epigastric vessels appeared to be smaller than the superficial system, so the decision to base the flap on the superficial vessels rather than the deep was finalized. Prior to transecting the entire flap, a sensory nerve was identified and preserved for a length of approximately 5 cm to create a sensate flap. After completely elevating the flap, the abdomen was closed in the standard fashion for an abdominoplasty. There was no need to reapproximate the rectus fascia because this layer was never violated during the procedure.

The flap (Fig. 5) was then taken to the recipient sister’s operating suite and placed in the mastectomy pocket prepared while the flap was harvested. To prepare the recipient site, the third costal cartilage was excised and the left internal mammary artery and vein were exposed. A sensory nerve was identified in the lateral axillary area and preserved to make this a sensate flap. Using the surgical microscope, the internal mammary artery and vein were sutured to the SIEA and vein via an end-to-end anastomosis. After the anastomoses were completed, there was excellent flap perfusion as well as strong signal from the venous Doppler probe placed around the venous anastomosis. The two ends of the nerves from the flap and chest wall were also approximated to improve the chances for appropriate sensation to the new breast. The final flap weight of 855 g appeared to be symmetrical in size to the contralateral breast, which underwent a mastopexy at the time of flap insetting. The flap was then inset with deep sutures. The procedure concluded and the recipient sister went to the surgical intensive care unit for overnight flap monitoring. The flap did well overnight and the patient was transferred to the floor the next day. By postoperative day 5, the distal inferior lateral aspect of the flap (zone 4) demarcated from ischemia that was noticed early in the postoperative period. For this reason the patient was taken back to the operating room for debridement under local anesthesia. The amount resected was 183 g. There was no evidence of flap loss other than the most distal aspect of the flap. As seen in Figure 6, the patient did very well and obtained an excellent result.

DISCUSSION
Because of the work of Dr. Murray, his principles of transplantation have been applied to many more cases of transplantation involving twins, including flap transplantation for breast reconstruction. The previous case reports are the first documented, successful cases of transferring abdominal skin and fat from one identical twin to another for the purpose of breast reconstruction. In fact, after reviewing the literature, these are the first cases of transferring any flap, via any technique, between twins for breast reconstruction. The procedure of choice in this situation and all cases of breast reconstruction with abdominal tissue at this institution is the use of either a DIEP or SIEA flap. A DIEP flap provides for many advantages over the standard TRAM flap. Because the perforator flap dissects the deep inferior epigastric artery and vein out of the rectus abdominis muscle, thereby leaving the muscle intact, there is reduced morbidity in the form of abdominal hernias and asymmetry. With an intact rectus muscle, there is no significant loss of abdominal muscle strength or function in contrast to TRAM flap patients.17,18 An additional advantage of the perforator flap over the TRAM is that operative time and cost are less for breast reconstruction with a perforator flap.19 Particularly in the case of transplanting tissue from one patient to another, the low donor site morbidity of the DIEP flap made this a much better option than the TRAM flap. The SIEA flap, which does not violate the rectus sheath at all, has even less donor site morbidity than the DIEP flap. Probably the most important issue in this case was that of the twins’ zygosity status. It was absolutely essential that these twins were indeed identical so that immunosuppressive therapy would not be needed.With the current ethical arguments regarding transplantation of tissue that, although very useful, is not necessary to sustain life, it was important that these patients were not subjugated to antirejection therapy that can have devastating effects on the ability to fight infection.20 Luckily, the technology exists such that there is statistical certainty that these twins were identical and not fraternal. Therefore, the recipient sister’s immune system should accept her donated flap as though it were her own tissue because, genetically speaking, it is.

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