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Purpose: Postmastectomy radiation therapy (PMRT) delivered to an immediate reconstruction increases the risk of surgical complications. Although acellular dermal matrix (ADM) has been used with immediate tissue expander (TE) reconstruction to improve cosmetic outcomes and minimize capsular contracture, there is a paucity of data on this approach in the setting of PMRT., Methods and Materials: Thirty-two patients with stage I to III breast cancer were treated with mastectomy, immediate TE-ADM reconstruction, and PMRT between 2009 and 2012 in a prospective single-arm study. The primary objective was the "success" rate, determined by the number of patients at 2 years after PMRT having an intact final reconstruction, no major complications, and a cosmetic outcome rated by a physician as excellent or good., Results: The median follow-up was 24 months. Final reconstruction status was known in 31 of 32 patients (96.9%; 1 patient left the country) and completed in 29 of 31 patients (93.5%; implant, n = 26; flap, n = 1; both, n = 2; none, n = 2). At 2 years, 6 patients were unevaluable (metastatic disease, n = 3; withdrawn consent, n = 1; left the country, n = 2). Of 26 evaluable patients, the success rate was 65.4% (17 of 26). Lack of success was the result of "fair" cosmesis (n = 2), infection (n = 2), severe capsular contracture (n = 1), major revision (n = 2), and no final reconstruction (n = 2). Most patients had good-to-excellent 2-year overall cosmesis based on patient perception (15; 62.5%) and physician evaluation (19; 79.2%)., Conclusions: To the best of our knowledge, this is the first dedicated prospective trial evaluating long-term cosmetic and complication outcomes in patients treated with immediate TE-ADM reconstruction followed by PMRT. Most patients (65.4%) met the success criteria in this prospective single-arm series. The great majority (93.5%) achieved final reconstruction; most had good-to-excellent overall cosmetic outcomes (79.2%). The results with longer follow-up will be of interest, and further investigation of strategies to optimize reconstruction with PMRT are warranted., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Implant-based breast reconstruction with an acellular dermal matrix is one of the most common procedures performed by plastic surgeons. Although numerous matrices are available, there is little literature comparing them. This study compares the rates of complications between two commonly used products: AlloDerm (human cadaveric) and SurgiMend (fetal bovine) acellular dermal matrices., Methods: A retrospective review of a single center's 6-year experience was performed for consecutive, immediate breast reconstructions with acellular dermal matrix from 2009 to 2014. The authors compared demographics and surgical characteristics between patients receiving AlloDerm versus SurgiMend. Multivariate logistic regression was used to determine any association between type of matrix and surgical complications and to identify other clinical predictors for complications., Results: A total of 640 patients underwent 952 reconstructions using AlloDerm [578 breasts (61 percent)] or SurgiMend [374 breasts (39 percent)]. The average follow-up was 587 days. Multivariate analysis revealed that type of matrix was not an independent risk factor for the development of complications. However, smoking, age, radiotherapy, and initial tissue expander fill volume were associated with increased risk of postoperative complications., Conclusions: Both AlloDerm and SurgiMend acellular dermal matrices demonstrate similar rates of major complications when used in immediate implant-based breast reconstruction. In contrast, preoperative radiation therapy, smoking, increasing age, and initial tissue expander fill volume are independent risk factors for postoperative complications. Reconstructive surgeons should take these findings into consideration when performing implant-based breast reconstruction with a dermal matrix.

In summary, if the abdomen cannot be used for a donor site, alternative flap selection is based on individual patient anatomy and body habitus, targeting the buttocks and upper thigh. Intraoperative repositioning may be required for ease in flap harvest and donor site closure, adding time to the procedure. Flap dissection is performed in the subfascial plane to avoid injury to the perforator vessels. Deep suspension sutures may be required to maintain the gluteal fold location.

Background: Acellular dermal matrix has become a common adjunct in prosthesis-based breast reconstruction. The authors' aim was to determine whether acellular dermal matrix use in immediate prosthesis-based breast reconstruction is associated with higher rate of complications., Methods: Over a 5½-year period at the Brigham and Women's Hospital, 470 postmastectomy defects were reconstructed immediately using tissue expanders or implants. These were divided into two groups: reconstructions with or without acellular dermal matrix. Data were collected on patient comorbidities, radiation, intraoperative tumescent solution use, prosthesis size, initial fill volume, and complications., Results: The risk for major infections that required prosthesis removal was elevated in the acellular dermal matrix group (4.9 versus 2.5 percent), but this increase did not reach statistical significance (p = 0.172). There was a statistically significant increase in overall wound infection rate in the acellular dermal matrix group (6.8 versus 2.5 percent, p = 0.031), but in a multivariate analysis, the use of acellular dermal matrix did not materialize as a significant risk factor for overall wound infection. Overall surgical complication rate was significantly higher in the acellular dermal matrix group at 19.5 percent, compared with the non-acellular dermal matrix group at 12.3 percent (p < 0.001). Other significant risk factors for overall surgical complication included smoking, higher body mass index, higher initial volume, and larger implant size., Conclusions: Patient selection for prosthesis reconstruction involving acellular dermal matrix should be judicious, especially among smokers and patients with elevated body mass index. Even though the use of acellular dermal matrix allows higher initial volumes and reduced number of expansions, one should be careful about putting in too high of an initial volume.

To evaluate the likelihood of requiring major corrective surgery (MCS) after modified radical mastectomy (MRM), immediate reconstruction and radiation therapy (RT) to the reconstructed breast. The study population consisted of 62 patients who underwent MRM and immediate breast reconstruction between 1990 and 1999, had postoperative radiation and at least one follow-up visit or procedure > or = 2 months after radiation. Reconstruction consisted of a pedicled transverse rectus abdominis myocutaneous flap in 42 patients, latissimus dorsi flap in five, latissimus dorsi plus implant in six, and implant alone in nine. Median follow-up time after reconstruction was 13 months (range: 2-58) for non-implant patients and 10 months (range: 4-57) for implant patients. The primary endpoint was the incidence of major complications requiring MCS. Ten patients (16%) underwent MCS between 1 and 28 months after radiation (median in these patients of 8 months). 4/47 non-implant patients (9%) underwent MCS, compared to 6/15 implant patients (40%). Of patients followed > or = 6 months after RT, 0/38 non-implant patients underwent MCS within 6 months compared to 3/13 (23%) implant patients (p = 0.01); of patients followed for > or = 12 months after RT, the rates of MCS within 12 months were 1/24 (4%) and 2/7 (29%), respectively (p = 0.12). Patients who undergo immediate reconstruction after mastectomy using an implant followed by radiation have a high rate of subsequent MCS. The difference in the rate of MCS between the implant and non-implant groups is significant in early follow-up. Patients considering an implant followed by RT should be apprised of this increased risk. Prospective studies of these risks and the cosmetic outcomes are warranted.

Objective: Review of available literature on the topic of breast reconstruction and radiation is presented. Factors influencing the decision-making process in breast reconstruction are analyzed. New trends of immediate breast reconstruction are presented., Summary Background Data: New indications for postmastectomy radiation have caused a dramatic increase in the number of radiated patients presenting for breast reconstruction. The major studies and their impact on breast cancer management practice are analyzed. Unsatisfactory results of conventional immediate reconstruction techniques followed by radiotherapy led to a new treatment algorithm for these patients. If the need for postoperative radiation therapy is known, a delayed reconstruction should be considered. When an immediate reconstruction is still desired despite the certainty of postoperative radiotherapy, reconstructive options should be based on tissue characteristics and blood supply. Autologous tissue reconstruction options should be given a priority in an order reflecting superiority of vascularity and resistance to radiation: latissimus dorsi flap, free TRAM or pedicled TRAM without any contralateral components of tissue, pedicled TRAM/midabdominal TRAM, and perforator flap., Conclusions: When the indications for postoperative radiotherapy are unknown, premastectomy sentinel node biopsy, delayed-immediate reconstruction, or delayed reconstruction is preferable.

Objective: To determine the rate of postmastectomy reconstruction and investigate the impact of socioeconomic status on the receipt of reconstruction., Summary Background Data: The National Comprehensive Cancer Network (NCCN) Outcomes Project is a prospective, multi-institutional database that contains data on all newly diagnosed breast cancer patients treated at one of the participating comprehensive cancer centers., Methods: The study cohort consisted of 2174 patients with DCIS and stage I, II, and III invasive breast cancer who underwent mastectomy at one of 8 NCCN centers. Rates of reconstruction were determined. Logistic regression analyses were used to evaluate whether socioeconomic characteristics are associated with breast reconstruction., Results: Overall, 42% of patients had breast reconstruction following mastectomy. Patients with Medicaid and Medicare were less likely to undergo reconstruction than those with managed care insurance; however, there was no difference for indemnity versus managed care insurance. Homemakers and retired patients had fewer reconstructions than those employed outside the home. Patients with a high school education or less were less likely to have reconstruction than those with more education. Race and ethnicity were not significant predictors of reconstruction., Conclusions: The reconstruction rate in this study (42%) is markedly higher than those previously reported. The type of insurance, education level, and employment status of a patient, but not her race or ethnicity, appear to influence the use of breast reconstruction. Because all patients were treated at an NCCN institution, these socioeconomic differences cannot be explained by access to care.

For circulating lymphocytes to migrate to inflammatory sites, they must first adhere to the target tissue endothelium with sufficient strength to overcome the shear forces of blood flow. We previously reported that dermal papillary vessels in acute graft-versus-host disease (aGVHD) support shear-resistant lymphocyte adherence. We now identify the relevant adhesion molecule(s) directing this binding, showing that interactions between lymphocyte CD44 and hyaluronic acid (HA) expressed on dermal vessels in aGVHD alone confer this shear-resistant attachment. Native HA deposits on vascular endothelium support lymphocyte adherence, whereas HA immobilized on plastic does not. HA expressed at dermal endothelium in aGVHD is thus specialized to support lymphocyte adherence under flow conditions, and CD44-HA interactions may contribute to lymphocytotropism to skin in aGVHD.

Failure of an ileal pouch-anal anastomosis may result in unsuccessful completion of the anastomosis or removal of an ischemic pouch. We report a technique for preservation of the muscular wall of the rectum after mucosal dissection, which allowed a successful delayed pull-through.

A locally active thrombolytic agent, human tissue-type plasminogen activator (t-PA), given over a finite time period (24 hours) by local infusion, maintains long-term microvascular patency (7 days) in a proven thrombosis model using an arterial inversion graft in the rabbit model. Thirteen rabbits in the control group and 16 rabbits in the experimental group underwent an arterial inversion graft followed by continuous infusion (24 hours) with human tissue-type plasminogen activator (experimental) or normal saline (control). No significant clinical bleeding or alteration of coagulation parameters was noted in hematologic studies in both experimental and control groups. Scanning electron microscopy of the postoperative human tissue-type plasminogen activator-perfused arteries suggests an interaction of the human tissue-type plasminogen activator with specific platelet receptors in reversing microvascular thrombosis by decreasing or preventing further platelet aggregation and adhesion. Human tissue-type plasminogen activator infused locally for a finite period (24 hours) allows adequate time for platelet metamorphosis to occur in converting a thrombogenic to a nonthrombogenic vessel surface. The clinical ramifications in preventing or reversing microvascular thrombosis in free-tissue transfers and replantation surgery are apparent. Further study in this area will enhance our understanding of the pathogenesis and prevention of microvascular thrombosis.

Flap prefabrication is dependent on the neovascular response that occurs between the implanted arteriovenous pedicle and the recipient tissue. Augmentation of this neovascular response with angiogenic growth factors would maximize flap survival and minimize the interval between pedicle implantation and flap rotation. Maximizing the biologic activity of endogenous growth factors would likewise positively impact upon flap survival. This study examined the role of basic fibroblast growth factor, a known potent angiogenic growth factor, on flap survival in a rabbit ear prefabrication model. Sucrose octasulfate, a substance that binds basic fibroblast growth factor, stabilizes it, and protects it from degradation, was also studied to determine its impact on flap survival. Flap survival was increased using basic fibroblast growth factor, sucrose octasulfate, and the two substances combined together. The use of substrates designed to maximize the biologic activity of endogenous growth factors, rather than relying on the artificial addition of exogenous growth factors, represents a new approach in the search for methods that will improve flap survival.

This study was designed to determine whether tissue expansion after vascular pedicle implantation would increase the survival area of prefabricated skin flaps. In 20 New Zealand white rabbits, the vascular pedicle consisting of the central artery and vein of the left ear was implanted into the neck. At the time of pedicle implantation a subcutaneous pocket was created measuring 5 x 14 cm beneath the implantation site. Tissue expanders of three different sizes and volumes were implanted in the rabbits of three treatment groups. No tissue expander was implanted in the animals of the control group. All flaps were transposed after 3 weeks to the contralateral ear, and flap survival was assessed 1 week later. The increased area of the flap survival was statistically significant in all three treatment groups compared to the nonexpanded flaps (P = 0.003, P = 0.004, P < 0.0001, respectively). In addition there was a statistically significant larger area of survival using a 100-cc expander measuring 5 x 14 cm (the same size as the elevated flap) compared to 40-cc (3 x 5 cm) or to 60-cc (4 x 8 cm) expanders (P < 0.001, P = 0.004, respectively). The one-way analysis of variance and the t-test were used to show statistical differences. We conclude that the time necessary for neovascularisation of the skin flap could be used to expand the tissue, not only increasing the amount of available tissue, but also enhancing the vascularity.

The role of growth factors in a variety of bone and soft tissue healing processes has been studied extensively in numerous recent models, yet little is known about the specific growth factors that may be playing a role in flexor tendon healing. We used a number of established protein purification techniques and bioassays to isolate and partially characterize a heparin-binding growth factor from unoperated canine tendons. Our data provide evidence that basic fibroblast growth factor, a potent angiogenic growth factor, is present in normal canine intrasynovial flexor tendons. We then studied repaired canine flexor tendons to further elucidate the role of growth factors in the tendon healing process. Heparin-sepharose elution profiles from three repair intervals (3, 10, and 17 days) were graphed and compared to known profiles of isolated growth factors. The three repair intervals demonstrated two elution profile peaks, consistent with varying amounts of platelet-derived growth factor and epidermal growth factor. Although additional experimentation is required to identify definitively the various protein isolates, these data provide compelling evidence that a variety of growth factors are present in uninjured and healing digital flexor tendons.

The descending branch of the lateral femoral circumflex artery is a large-caliber artery that passes obliquely across the upper third of the thigh and descends between the vastus lateralis and rectus femoris muscles. It sends perforators through the septum between these muscles and through the vastus lateralis muscle and supplies a large area of skin on the anterolateral aspect of the thigh. We report our experience with our first 44 consecutive anterolateral thigh flaps, which were used for a variety of soft-tissue deficits. Twenty-five of these flaps were used for lower extremity reconstruction. 10 were used in the upper extremity, and 9 were used in the head and neck. The overall success rate was 96%. Six flaps required reoperation; of these, 2 flaps were lost, one from a venous thrombosis and the other from arterial thrombosis, both of which were in the lower extremity. In approximately one third of cases, the flap was raised as a septofasciocutaneous flap, but in two thirds it was necessary to include a small segment of vastus lateralis muscle as well as fascia with the flap. The flap has been particularly useful for lower extremity reconstruction, and in patients who are not fit for general anesthesia, it is possible to perform the flap transfer with epidural anesthesia. The flap has the advantage of a long vascular pedicle with large-caliber vessels and thus is suitable as a flow-through flap. It may also be sensate and has provided a versatile soft-tissue coverage option with minimal long-term donor-site complications.

In a group of patients where breast reconstruction was performed at the time of mastectomy, the incidence of complications was studied. One hundred one consecutive patients had an autologous reconstruction using the transverse rectus abdominis musculocutaneous flap, and 115 consecutive patients had a prosthetic reconstruction with tissue expanders or with tissue expander and/or implant. One patient in the autologous reconstruction group had a cardiac arrhythmia requiring monitoring, but there were no other serious complications. Infection was more common in the group undergoing prosthetic reconstruction (5% compared with 3% in the autologous reconstruction group). A total of 8% of the patients in the group undergoing prosthetic reconstruction had to have their implants removed because of infection or exposure of the implant. Seven percent of the transverse rectus abdominis musculocutaneous flap patients had significant necrosis of a portion of the flap. Secondary surgical revision of the reconstructed breast was much more common (20%) in the prosthetic reconstruction group compared with 6% in the autologous reconstruction group.

Neovascularisation of thin skin flaps after arteriovenous pedicle implantation (flap prefabrication) and the impact of the delay mechanism on the viability of these flaps were investigated. Twenty-four full thickness skin flaps were raised in twelve New Zealand white rabbits. Delay incisions were made at the lateral borders of the planned flaps at the same time as pedicle implantation, 1 week before pedicle implantation, or 1 week after pedicle implantation and the flaps based on the implanted vessels raised at 2 weeks after implantation. Flap survival assessed at 1 week was found to be improved when flap delay was performed 1 week before or after pedicle implantation. Angiographic studies demonstrated an increased density and linearity of the vascular pattern in these delay group flaps. The combination of the time-tested concept of delaying a flap with the newer technique of flap prefabrication appears to improve flap viability.

As flap prefabrication becomes a more commonly used clinical tool, it is necessary to investigate the limitations of this technique. Reconstructive procedures of the face often require "custom fitted" flaps to satisfy esthetic demands. This study examines and compares the safety of manipulating thin prefabricated skin flaps versus established axial pattern skin flaps. Twenty-seven New Zealand white rabbits were used to determine if prefabricated flaps can be folded 180 degrees around the edge of the rabbits' ears. The survival of these folded prefabricated flaps was compared with the survival of axial pattern flaps sutured into an identically recipient site. In addition, flaps prefabricated in the same manner were sutured onto a straight recipient bed to evaluate the viability of the newly vascularized tissue. The folded prefabricated flaps had reduced survival (56%) compared to equivalent folded axial pattern flaps (85%), P < 0.005. The nonmanipulated prefabricated flaps and axial pattern flaps survived completely.

Objective: The authors prospectively studied the impact of immediate breast reconstruction on patients undergoing mastectomy., Summary Background Data: Despite the advocation of a breast-conserving approach to the treatment of breast cancer, many women continue to medically require or choose mastectomy for the treatment of breast cancer. In recent years, immediate breast reconstruction has become an alternative to either mastectomy alone or to delayed reconstruction., Methods: A prospective database of 216 patients who underwent mastectomy with immediate reconstruction was established. In this series, 94 procedures involved implants or tissue expanders, and 124 tissue transfers were performed., Results: The overall complication rate was 15.3%; only 9% of patients who underwent autologous tissue transfers required secondary procedures. When implants were performed, the overall rate of prosthetic loss was 8%. The majority of patients (n = 101) underwent transverse rectus abdominis musculocutaneous (TRAM) flaps. Twenty-six of the 38 (17.5%) patients who required transfusion were from this group. Partial flap losses in this group (7%) were correlated to a history of heavy smoking. With a median follow-up of 33.2 months, only two patients had recurred locally. According to patient opinion, autologous tissue transfers resulted in a statistically better cosmetic result., Conclusions: Immediate reconstruction can be performed safely and with excellent cosmetic results.

We have developed a new model of thin flap prefabrication in the rabbit with an exteriorised vascular pedicle in a skin tube. Study of these prefabricated flaps after transfer demonstrated that distal flap survival improved as the interval between implantation and flap transfer increased. Exteriorising the pedicle minimises both donor deformity and pedicle trauma and allows easier experimental study of the neovascularisation process in flap prefabrication.

Recent studies have demonstrated an intrinsic neovascular response in intrasynovial healing tendons, introducing the possibility of mitogenic and/or angiogenic capability of intrasynovial tendon. To explore this hypothesis, healing canine flexor tendons were treated with early passive mobilization and the repair sites analysed at three, ten and 17 days. Specimens were mechanically digested and subjected to a standard BALB/c 3T3 mitogenic assay, which measures the capacity of tissue extracts to induce DNA synthesis and cell division in fibroblasts. Results revealed that both control and repaired flexor tendons possessed mitogenic activity, with the greatest activity observed in control specimens. Decreasing activity was noted as the time between repair and analysis increased. These data provide increasing evidence for the flexor tendon's active role in the healing process, and support the concept that mitogenic or growth-promoting factors are associated with flexor tendons and may be released following injury, during the early stages of healing.

Four techniques for permanent skin replacement with skin substitutes are described. A claim of superiority to conventional skin grafting on upper extremity and hand burns is not made, but some clinical observations and histologic evidence of different healing characteristics are shown. The composite grafts described appear to effectively replace the bilayered structure of skin and seem to have good subjective resistance to shear forces. If the skin replacement is durable and heals with less scarring than conventional skin grafts, the inexorable course to stiffness and contracture may be altered. Further basic science and clinical investigation may provide us with a better way of managing these difficult problems.

A patient who has undergone successful replantation of seven of eight amputated digits is presented. Survival in the last viable digit was seen 39 hours after amputation with cold ischemia preservation. No graded ischemia-related changes in the digits have been appreciated over 35 months of follow-up.

A new potent thrombolytic agent, human tissue type plasminogen activator (t-PA), has become available for study through recombinant DNA technology. In this series of experiments, we have tested t-PA in a reliable microvascular thrombosis model previously developed in our laboratory. Its action in preventing thrombus formation and lysing fresh clot by direct local infusion and systemic infusion was tested. The results revealed that t-PA was able to keep locally infused vessels open for 4 hours and reopen them after they were allowed to clot in 100 percent of the animals tested. Those vessels exposed only to systemic levels of t-PA achieved by the same local infusion remained thrombosed and were unaffected. Laboratory studies showed no evidence of activation of the systemic lytic state or alteration in coagulation parameters. t-PA has proved to be a protein with characteristics that make it attractive for use in microvascular surgery. The results suggest that further research may lead the way toward clinical use.