Expander prosthesis and DIEP flaps in delayed breast reconstruction: Sensibility, patient-reported outcome, and complications in a five-year randomised follow-up study.

Breast reconstruction is a given choice for many women following mastectomy. There are a multitude of methods available today, and thus, comparative studies are essential to match patients with suitable methods. The aim of this study was to compare 5-year outcomes following delayed breast reconstruction with expander prosthesis (EP) and with deep inferior epigastric perforator (DIEP) flaps. Seventy-three patients, previously randomised to either a permanent EP or a DIEP flap breast reconstruction, were invited for a 5-year follow-up. Assessments included symmetry measurements, breast sensibility with Semmes-Weinstein monofilaments and patient-reported outcome (PRO) with the BREAST-Q. Complications within the first 5 postoperative years were recorded. Additionally, BREAST-Q questionnaires were collected from non-randomised patients with an EP breast reconstruction. Between 2019 and 2022, 65 patients completed the follow-ups. Symmetry and PRO were significantly higher in the DIEP flap group. However, EP-reconstructed breasts were significantly more sensate and demonstrated areas with protective sensibility, unlike the DIEP flap breasts. The overall complication rates were comparable between the two groups (p = 0.27). Regression analysis identified body mass index as a risk factor for reoperation in general anaesthesia and for wound infection. No significant differences were found in a comparison of the randomised and the non-randomised EP groups' BREAST-Q results. This randomised 5-year follow-up study found PRO to be favourable following a DIEP flap reconstruction and sensibility to be better in EP reconstructions. The complication rates were comparable; however, longer follow-ups are warranted to cover the complete lifespans of the two breast reconstruction methods.

Evaluation of an assessment scale for aesthetic outcome in breast reconstructions based on digital photos in both 2D and 3D format.

The aesthetic outcome is crucial in a breast reconstruction. Our aim was to evaluate the intra- and interrater reliability of an aesthetic outcome assessment scale with digital photos of breast reconstructions in two-dimensional (2D) and three-dimensional (3D) format. Thirty-three women with delayed breast reconstructions, consecutively participating in a five-year follow-up between November 2019 and June 2021, were included in the study. Of these, 14 were reconstructed with an expander prosthesis (EP) and 19 with a deep inferior epigastric perforator (DIEP) flap. Photos of the breasts were assessed in 2D and 3D format by expert, layman and patient panels. Data were analysed with the weighted kappa (wk) statistics. The intrarater agreements were moderate to substantial, with wk between 0.66 and 0.73 for the panels. Within the panels, the interrater agreements were 0.46-0.62. Moderate agreements were found between the matched 2D and 3D format photos (wk 0.62-0.66). The patient panel graded scar appearance worse in 3D compared with 2D format. In all panels, there was a tendency towards DIEP flap reconstructions receiving higher aesthetic outcome grades compared with EP. Thus, the aesthetic outcome assessment scale demonstrated acceptable agreements between the individual panellists and within the panels. Scars captured in 3D format may provide a greater resemblance to the reality compared with 2D. Implications for clinics remain to be further studied.

Assessment of local tissue water in breasts following breast reconstruction with an expander prosthesis or DIEP flap.

The role of breast oedema in breast reconstruction is unknown. Therefore, our aim was to investigate local tissue water (LTW) and breast oedema-related symptoms in breasts reconstructed with either an expander prosthesis (EP) or with a deep inferior epigastric perforator (DIEP) flap at a minimum of one year postoperatively. Sixty-eight patients randomised to breast reconstruction with an EP or DIEP flap completed follow-up. Objective evaluation was performed at a mean of 25 (standard deviation, SD 9.5) months following breast reconstruction, and included measurements of breast volume and LTW with the MoistureMeterD® instrument. The patients completed the BREAST-Q questionnaire pre- and postoperatively. No significant differences in LTW were found when comparing EP and DIEP flap reconstructed breasts. The reconstructed breasts had an increase in LTW compared with the non-operated contralateral breasts. The BREAST-Q responses related to breast oedema symptoms were overall low and the median responses ranged from 1 to 2. A score of 1 indicated that symptoms were experienced 'None of the time'. Our findings indicate that mastectomy followed by breast reconstruction inflicts damage on the lymphatic system, shown as an increase in LTW. However, no breast oedema-related symptoms were reported in the BREAST-Q questionnaire, and therefore, we consider our objective results to be below a potential threshold for symptomatic breast oedema. A threshold for clinical indication of breast oedema remains to be defined.

A short-term comparison of expander prosthesis and DIEP flap in breast reconstructions: A prospective randomized study.

BACKGROUND: There is yet no clear consensus on which method is preferable in secondary breast reconstructions, prosthesis, or autologous tissue. METHODS: In this first prospective randomized study, 29 women underwent reconstruction with expander prosthesis (EP) and 44 with deep inferior epigastric perforator (DIEP) flap. Inclusion started in 2012 and ended in 2018. Demographic data, complications, surgery time, hospital days, and consulting visits were recorded. Patient satisfaction was evaluated pre- and postoperatively using the BREAST-Q questionnaire. Health care costs were calculated based on rates from the financial year 2018. Here, we report the results related to the surgery and the first 30 postoperative days. RESULTS: The two groups were comparable regarding demographics and clinical characteristics. Satisfaction with breasts, measured with BREAST-Q, was significantly higher in patients who had undergone reconstruction with DIEP flap compared with EP. Within 30 days after breast reconstruction, significantly fewer women (n = 2) in the EP group suffered complications compared to the DIEP flap group (n = 16; p < 0.01). The health care cost was also significantly higher in the DIEP flap group relative to the EP group (p < 0.01). DISCUSSION: This patient cohort will be studied systematically over time, and results concerning the need for complementary surgery, costs, esthetics, and the patient-reported outcome (PRO) will be reported in future work. In this short-term report, EP seems to be preferable in regard to cost and complications, and DIEP flap is to choose from the patient's perspective.

Smoking increases donor site complications in breast reconstruction with DIEP flap.

OBJECTIVE: Reconstruction with deep inferior epigastric perforator flap (DIEP) is considered to be the first choice for autologous breast reconstruction. The primary aims of this retrospective study were to find out if differences in smoking habits and BMI are useful predictors for postoperative complications in DIEP surgery. METHODS: Three hundred and one patients were included. Data regarding smoking habits, BMI, age at surgery, total and final flap weight, abdominal scars, parity, number of perforators, chemotherapy, post mastectomy radiation therapy, and preoperative mapping of perforators with either Computer Tomography Angiography or hand-held ultra sound Doppler were collected. Complications that occurred in the first 30 postoperative days were taken into account. RESULTS AND CONCLUSIONS: It was found that former smokers had a risk for donor site complication more than double that of never smokers (OR =2.12, CI =1.10-4.10, p = 0.025). Differences in BMI within the range from 18-33.7 did not have any significant impact on complication rates, neither at the donor site nor at the breast.

Blood flow dynamics and sensitivity in breasts after reconstruction with DIEP-flap.

A method of breast reconstruction is based on the Deep Inferior Epigastric Perforator (DIEP) technique. Skin and fat are transplanted from the abdomen to the chest; blood vessels are reconnected through microsurgery. Nerves are, however, left unconnected. This study aims to evaluate the blood flow and reinnervation of blood vessels and skin in breasts reconstructed by DIEP flaps without neural repair. In all, DIEP flaps of 10 patients were tested at an average of 16.3 months postoperatively. Blood flow was assessed by PeriScan PIM II System, both before and after indirect heating. Tactile perception threshold was assessed by Semmes-Weinstein monofilament and thermal sensibility by SENSELab MSA Thermotest. The patients' contralateral breasts were used as controls. The blood flow of the flaps was statistically significantly lower than in the control breasts, both before and after indirect heating. The change in blood flow after indirect heating did, however, not significantly differ when comparing the breasts. All flaps regained deep pressure sensibility in all four quadrants. Five patients regained even better sensibility in one of their quadrants. Seven patients regained perception of cold stimuli, five perceived warmth. This study has shown that skin blood flow regulation is present in DIEP flaps 1 year after reconstruction. Blood flow dynamics are very similar to those in the normal breast. There is also a recovery of tactile and thermal sensibility, but this study has not shown any clear parallels between recovery blood flow, tactile sensibility and thermal sensibility.

Cell suspensions of autologous keratinocytes or autologous fibroblasts accelerate the healing of full thickness skin wounds in a diabetic porcine wound healing model.

Autologous dermal fibroblasts may be useful in the treatment of diabetic skin wounds. We hypothesized that cultured fibroblasts or cultured keratinocytes would not only survive in a hyperglycemic wound environment but also enhance the rate of re-epithelialization. We previously developed a new porcine model of delayed cutaneous wound healing in the diabetic pig. Full thickness wounds were created on the dorsum and dressed with polyurethane chambers to keep the wounds wet and to allow for wound fluid monitoring. Suspensions of either autologous fibroblasts or autologous keratinocytes were injected into full thickness wounds and compared with wounds treated in a wet environment in normal saline. Serum glucose and wound fluid glucose concentrations were monitored daily. Wound contraction was monitored and biopsies taken on day 12. Transplantation of suspensions of autologous fibroblasts or autologous keratinocytes enhanced re-epithelialization of cutaneous full thickness wounds. Wounds treated with autologous fibroblasts showed a re-epithelialization rate of 86.75% and wounds treated with autologous keratinocytes showed a re-epithelialization rate of 91.3%. This is compared with a re-epithelialization rate of 56.8% seen in the normal saline treated wounds. While previous studies have shown fibroblasts suspension to have little effect in the treatment of full thickness wounds in nondiabetic wounds, this study shows a clear beneficial effect in the use of fibroblast or keratinocyte suspensions for the cutaneous healing of diabetic wounds in pigs.

Insulin-like growth factor-1 gene therapy and cell transplantation in diabetic wounds.

BACKGROUND: Impaired wound healing is a frequent phenomenon in diabetes mellitus. However, little is known of the fundamental cause of this pathology. The present study examined the effect of human insulin-like growth factor (hIGF)-1 overexpression in combination with autologous cell transplantation to diabetic wounds in a preclinical large-animal model. METHODS: Diabetes was induced in Yorkshire pigs with streptozotocin. Keratinocytes were cultured and transfected with hIGF-1 or LacZ transgene. Plasmids were lipoplexed with either Lipofectin or Lipofectamin 2000. Transgene expression was assessed by enzyme-linked immunosorbent assay or X-gal staining. For in vivo studies, full-thickness wounds were created and dressed with a sealed chamber. Transfected cells were transplanted into the wounds. Wound contraction was monitored and biopsies were obtained for measurement of re-epithelialization. Wound fluid was collected and analysed for IGF-1 concentrations. RESULTS: Quantification showed up to 740 ng/ml IGF-1 in vitro and significantly higher concentrations over 14 days compared to controls for the Lipofectamin 2000 group. Lipofectin-mediated gene transfer showed peak expression on day 2 with 68.5 ng/ml. In vivo, transfected cells showed peak expression of 457 ng/ml at day 1, followed by subsequent decline to 5 ng/ml on day 12 with Lipofectamin 2000. For Lipofectin, no significant IGF-1 expression could be detected. Gene therapy caused significantly faster wound closure (83%) than both controls (native-cell therapy = 57%; control wounds = 32%). CONCLUSIONS: The present study demonstrates that optimized nonviral gene transfer increased IGF-1 expression in diabetic wounds by up to 900-fold. This high IGF-1 concentration in combination with cell therapy improved diabetic wound healing significantly.

Impaired wound healing in an acute diabetic pig model and the effects of local hyperglycemia.

Diabetic wounds result in significant morbidity, prolonged hospitalization, and enormous health-care expenses. Pigs have been shown to have wound healing resembling that in humans. The aim of this study was to develop a large-animal model for diabetic wound healing. Diabetes was induced by streptozotocin injection in Yorkshire pigs. Full-thickness wounds were created and dressed with a sealed chamber. Nondiabetic pigs with or without high glucose wound fluid concentration served as controls. Glucose concentration in serum and wound fluid was measured and collected. Wound contraction was monitored, and biopsies were obtained for measurement of reepithelialization. Wound fluid was analyzed for insulin-like growth factor-1 (IGF-1), platelet-derived growth factor, and transforming growth factor. Glucose concentration in wound fluid initially followed serum levels and then decreased to undetectable on day 9. Reepithelialization was significantly delayed in diabetic pigs. In nondiabetic pigs, wounds treated in a local hyperglycemic environment, and thus excluding the effects of systemic hyperglycemia, showed no difference in wound closure compared with controls. This suggests that delayed wound healing in diabetes is not induced by local high-glucose concentration itself. Analysis of growth factor expression showed a marked reduction in IGF-1 in the diabetic wounds. Diabetic pigs have impaired healing that is accompanied by a reduction of IGF-1 in the healing wound and is not due to the local hyperglycemia condition itself.

Cell suspension cultures of allogenic keratinocytes are efficient carriers for ex vivo gene transfer and accelerate the healing of full-thickness skin wounds by overexpression of human epidermal growth factor.

The concept of using growth factor therapy to induce wound repair has been endorsed in studies that show reduced growth factors in wound fluid from chronic and aged wounds. In this study, we used cell suspensions of allogenic keratinocytes as gene-delivery vehicles for human epidermal growth factor (hEGF) and analyzed their impact on wound repair in a porcine wound-healing model. Full-thickness wounds were created on the backs of six Yorkshire pigs and covered with a wound chamber to create a wet wound-healing environment. First, 5 x 10(5) allogenic, autogenic, or mixed keratinocytes were transplanted into wounds and healing parameters were analyzed. Second, we measured long-term reepithelialization and contraction rates from day 8 until day 35. In the third experiment, allogenic keratinocytes were transfected with an hEGF-expressing plasmid pCEP-hEGF and transplanted in full-thickness wounds to improve repair. Wounds treated with autogenic, allogenic, or mixed keratinocytes showed a significantly higher rate of reepithelialization relative to saline-treated control wounds. Repetitive biopsies indicated that the use of allogenic keratinocytes did not lead to long-term wound breakdown. Wounds treated with hEGF-expressing allogenic keratinocytes reepithelialized faster than wounds treated with allogenic keratinocytes or control wounds. With a peak hEGF expression of 920.8 pg/mL, hEGF was detectable until day 5 after transplantation compared with minimal hEGF expression in control wounds. This study shows that allogenic keratinocytes can serve as efficient gene transfer vehicles for ex vivo growth factor delivery to full-thickness wounds and overexpression of hEGF further improves reepithelialization rates.

Safety evaluation of topically applied amitriptyline in porcine full-thickness wounds.

BACKGROUND AND OBJECTIVES: The tricyclic antidepressant amitriptyline is frequently used in pain clinics for management of pain. It has also been suggested that topical application of amitriptyline could be useful for the treatment of neuropathic pain. In this report we investigated the effect of amitriptyline on porcine full thickness wounds resembling excised burn wounds. We assessed if daily topical application of amitriptyline into the wound chambers for 10 days impedes wound healing as measured by (1) wound contraction and (2) histopathological findings. METHODS: Full-thickness wounds measuring 1.5 cm square were created on the dorsum of Yorkshire pigs and were enclosed in polyurethane wound chambers. Amitriptyline was applied daily at various concentrations. Bupivacaine (0.5%) or normal saline were used as controls. Daily wound serum levels were obtained and the level of amitriptyline and nortriptyline obtained. Pictures were taken daily and the wound surface analyzed for contraction. Cross-sectional, full-thickness skin biopsies were obtained at days 2, 8 and 10 and evaluated microscopically for re-epithelialization, inflammation, and necrosis. RESULTS: The high serum level of amitriptyline and nortriptyline did not affect wound healing; re-epithelialization, wound contraction, and inflammation were not significantly different between amitriptyline and control groups. CONCLUSION: Amitriptyline at the concentrations of 0.0625% and 0.125% applied daily via chambers covering wounds in a full-thickness pig excision model has no overt toxic effect on wound healing as measured by wound contraction and histological assessment.