Efficacy of In Vivo Electroporation-Mediated IL-10 Gene Delivery on Survival of Skin Flaps.

Despite advances in understanding the underlying mechanisms of flap necrosis and improvement in surgical techniques, skin flap necrosis after reconstructive surgery remains a crucial issue. We investigated the efficacy of electroporation-mediated IL-10 gene transfer to random skin flap with an aim to accelerate wound healing and improve skin flap survival. Nine male Wistar rats (300-330 g) were divided in two groups (a) control group (n = 5), only surgery no gene transfer, and (b) experimental group, received electroporation-mediated IL-10 gene transfer 24 h before the surgery as prophylaxis (n = 4). Random skin flap (McFarlane) was performed in both groups. Planimetry, Laser Doppler imaging, and immunohistochemistry were used to evaluate the effect of IL-10 gene transfer between study groups at day 7. Electroporation-mediated IL-10 gene transfer decreased percentage of flap necrosis (p value = 0.0159) and increased cutaneous perfusion compared to the control group (p value = 0.0159). In addition, Spearman's rank correlation showed a significant negative correlation between percentage of flap necrosis and Laser Index (p value = 0.0083, r -0.83, respectively). Furthermore, significantly higher mean CD31+ vessel density was detected in the experimental group compared to the control group (p value = 0.0159). Additionally, semi-quantitative image analysis showed lower inflammatory cell count in experimental group compared to control group (p value = 0.0317). In vivo electroporation-mediated IL-10 gene transfer reduced necrosis, enhanced survival and vascularity in the ischemic skin flap.

Laser doppler imaging as additional monitoring after digital replanting: A prospective study.

BACKGROUND: Despite various exisiting monitoring methods, there is still a need for new technologies to improve the quality of post-operative evaluation of digital replantation. The purpose of the study is using a laser Doppler imaging device (Easy-LDI) as an additional tool to assess perfusion. In this method, the changes in the frequency of the laser ligth provide information regarding perfusion of the monitored tissue. PATIENTS AND METHODS: This study included seven patients (10 fingers; age of patients: 21-57 years) who suffered from a total (n = 6) or subtotal amputation (n = 4) due to accidents. In addition to hourly standard monitoring with clinical evaluation and skin thermometry, revascularized fingers were hourly monitored with Easy LDI for 48 h. RESULTS: LDI measurement values ranged between 0.8 and 223 (mean 90.62 ± 21.42) arbitrary perfusion units (APU). The mean LDI values before and after revascularization were 7.1 ± 2.85 and 65.30 ± 30.83 APU, respectively. For the successful revascularized fingers (8 of 10 fingers) values from 19 to 223 APU (mean 98.52 ± 15.48) were demonstrated. All of the replants survived, but due to venous occlusion two digits required revision 12 and 35 h after revascularization, respectively. In the two cases, Easy-LDI also showed a constant and slow decline of the perfusion values. Furthermore, Pearson normalized correlation coefficient showed a positive significant correlation between temperatures of the replants and LDI-values (P < .001, r = +0.392) and a negative significant correlation between Δtemperature and LDI-values (P < .001, r = -0.474). CONCLUSION: The LDI-device might be a promising additional monitoring technique in detection of perfusion disturbance in monitoring digital replantations.

A retrospective study of 1- versus 2-cm excision margins for cutaneous malignant melanomas thicker than 2 mm.

BACKGROUND: Most guidelines recommend at least 2-cm excision margin for melanomas thicker than 2 mm. OBJECTIVE: We evaluated whether 1- or 2-cm excision margins for melanoma (>2 mm) result in different outcomes. METHODS: This is a retrospective cohort study on patients with melanomas (>2 mm) who underwent tumor excision with 1-cm (228 patients) or 2-cm (97 patients) margins to investigate presence of local recurrences, locoregional and distant metastases, and disease-free and overall survival. RESULTS: In all, 325 patients with mean age of 61.84 years and Breslow thickness of 4.36 mm were considered for the study with a median follow-up of 1852 days (1995-2012). There was no significant difference in the frequency of locoregional and distant metastasis between the 2 groups (P = .311 and .571). The survival analysis showed no differences for disease-free (P = .800; hazard ratio 0.948; 95% confidence interval 0.627-1.433) and overall (P = .951; hazard ratio 1.018; 95% confidence interval 0.575-1.803) survival. LIMITATIONS: The study was not prospectively randomized. CONCLUSIONS: Our study did not show any significant differences in important outcome parameters such as local or distant metastases and overall survival. A prospective study testing 1- versus 2-cm excision margin is warranted.

Estrogen induces nitric oxide production via nitric oxide synthase activation in endothelial cells.

INTRODUCTION: 17ß-estradiol (E2) has been found to induce vasodilation in the cardiovascular system and at physiological levels, resulting in prevention of cerebral vasospasm following subarachnoid hemorrhage (SAH) in animal models. The goal of this study was to analyze the cellular mechanism of nitric oxide (NO) production and its relation to E2, in vitro in brain and peripheral endothelial cells. METHODS: Human umbilical endothelial cells (HUVEC) and brain endothelial cells (bEnd.3) were treated with estradiol (E2, 0.1, 10, 100, and 1,000 nM), and supernatant was collected at 0, 5, 15, 30, 60, and 120 min for nitric oxide metabolome (nitrite, NO2) measurements. Cells were also treated with E2 in the presence of 1400W, a potent eNOS inhibitor, and ICI, an antagonist of estradiol receptors (ERs). Effects of E2 on eNOS protein expression were assessed with Western blot analysis. RESULTS: E2 significantly increased NO2 levels irrespective of its concentration in both cell lines by 35 % and 42 % (p < 0.05). The addition of an E2 antagonist, ICI (10 µM), prevented the E2-induced increases in NO2 levels (11 % p > 0.05). The combination of E2 (10 nM) and a NOS inhibitor (1400W, 5 µM) inhibited NO2 increases in addition (4 %, p > 0.05). E2 induced increases in eNOS protein levels and phosphorylated eNOS (eNOS(p)). CONCLUSIONS: This study indicates that E2 induces NO level increases in cerebral and peripheral endothelial cells in vitro via eNOS activation and through E2 receptor-mediated mechanisms. Further in vivo studies are warranted to evaluate the therapeutic value of estrogen for the treatment of SAH-induced vasospasm.

Post-operative monitoring of free muscle transfers by Laser Doppler Imaging: A prospective study.

PURPOSE: Despite different existing methods, monitoring of free muscle transfer is still challenging. In the current study we evaluated our clinical setting regarding monitoring of such tissues, using a recent microcirculation-imaging camera (EasyLDI) as an additional tool for detection of perfusion incompetency. PATIENTS AND METHODS: This study was performed on seven patients with soft tissue defect, who underwent reconstruction with free gracilis muscle. Beside standard monitoring protocol (clinical assessment, temperature strips, and surface Doppler), hourly EasyLDI monitoring was performed for 48 hours. Thereby a baseline value (raised flap but connected to its vascular bundle) and an ischaemia perfusion value (completely resected flap) were measured at the same point. RESULTS: The mean age of the patients, mean baseline value, ischaemia value perfusion were 48.00 ± 13.42 years, 49.31 ± 17.33 arbitrary perfusion units (APU), 9.87 ± 4.22 APU, respectively. The LDI measured values in six free muscle transfers were compatible with hourly standard monitoring protocol, and normalized LDI values significantly increased during time (P < 0.001, r = 0.412). One of the flaps required a return to theatre 17 hours after the operation, where an unsalvageable flap loss was detected. All normalized LDI values of this flap were under the ischaemia perfusion level and the trend was significantly descending during time (P < 0.001, r = -0.870). CONCLUSION: Due to the capability of early detection of perfusion incompetency, LDI may be recommended as an additional post-operative monitoring device for free muscle flaps, for early detection of suspected failing flaps and for validation of other methods.

Relative indexes of cutaneous blood perfusion measured by real-time laser Doppler imaging (LDI) in healthy volunteers.

We used real-time LDI to study regional variations in microcirculatory perfusion in healthy candidates to establish a new methodology for global perfusion body mapping that is based on intra-individual perfusion index ratios. Our study included 74 (37 female) healthy volunteers aged between 22 and 30 years (mean 24.49). Imaging was performed using a recent microcirculation-imaging camera (EasyLDI) for different body regions of each volunteer. The perfusion values were reported in Arbitrary Perfusion Units (APU). The relative perfusion indexes for each candidate's body region were then obtained by normalization with the perfusion value of the forehead. Basic parameters such as weight, height, and blood pressure were also measured and analyzed. The highest mean perfusion value was reported in the forehead area (259.21APU). Mean perfusion in the measured parts of the body correlated positively with mean forehead value, while there was no significant correlation between forehead blood perfusion values and room temperature, BMI, systolic blood pressure and diastolic blood pressure (p=0.420, 0.623, 0.488, 0.099, respectively). Analysis of the data showed that perfusion indexes were not significantly different between male and female volunteers except for the ventral upper arm area (p=.001). LDI is a non-invasive, fast technique that opens several avenues for clinical applications. The mean perfusion indexes are useful in clinical practice for monitoring patients before and after surgical interventions. Perfusion values can be predicted for different body parts for patients only by taking the forehead perfusion value and using the perfusion index ratios to obtain expected normative perfusion values.

[The risk-reducing mastectomy: unnecessary hysteria or life-saving prophylaxis?]. / Die prophylaktische Mastektomie: unnötige Hysterie oder nötige Vorsorge.

The prophylactic (risk-reducing) mastectomy is a world-wide recognized method for specifically treating the increased breast cancer risk in patients showing a BRCA1 and/or BRCA2 mutation as well as other patient groups at increased breast cancer risk. This option should be offered to all patients having the pertinent risk profile. Breast reconstruction is an integral part of the risk-reducing mastectomy procedure and all possible methods of breast reconstruction, especially autologous tissue reconstruction should be offered to all patients having a medical indication and desiring this surgical treatment. These patients are best managed in certified Breast Care Centres where the different medical and surgical specialists can address interdisciplinary all aspects of genetic counselling, preoperative counselling, mastectomy and reconstructive techniques as well as the necessary postoperative surveillance.

The extended diep flap: extending the possibilities for breast reconstruction with tissue from the lower abdomen.

BACKGROUND: The classical DIEP-flap is considered state-of-the-art in microsurgical autologous breast reconstruction. Some patients may require additional volume to match the contralateral breast. This quality control study prospectively evaluates the feasibility and outcome of a surgical technique, which pursues the volumetric augmentation of the DIEP-flap by harvesting of additional subscarpal fat tissue cranial to the classical flap border. PATIENTS AND METHODS: For radiologically based estimation of volumetric flap-gain potential, abdominal CT-scans of 10 Patients were randomly selected and used for computerized volumetric estimates. Surgical evaluation of the technique was prospectively performed between 09/2009 and 09/2010 in 10 patients undergoing breast reconstruction with extended DIEP-flap at two institutions. The outcome regarding size, volume, and symmetry was evaluated. RESULTS: Radiologically, the mean computed volume gain of an extended DIEP was 16.7%, when compared with the infraumbilical unilateral flap volume. Clinically, the intraoperatively measured mean volume gain was of 98.6 g (range: 75-121 g), representing 13.8% of the flap volume. All 10 flaps survived without revision surgery. In three flaps, minor fat necrosis occurred in zone III and was treated conservatively. No fat necrosis was observed in the extended flap area. CONCLUSIONS: In this first prospective series, the extended DIEP-flap proved to be feasible, reliable and safe for its use in breast reconstruction. Both radiological estimation and intraoperative measurements demonstrated a statistically significant volume gain with no complications in the extended area. The technique is of benefit in selected patients requiring additional reconstructive volume than the one achieved with the classical DIEP-flap. LEVEL OF EVIDENCE: Therapeutic Level IV.

[Surgical therapy for reconstruction of body shape and contour following massive weight reduction]. / Chirurgische massnahmen zur wiederherstellung der körperform und -konturnach massiver gewichtsreduktion.

The consequences of massive weight loss through bariatric procedures as well as diet are overall positive. However, the sequelae of massive weight loss present themselves as soft tissue redundancies in the areas of the lower abdomen, upper thigh, upper arm and breast as well as face and neck. This condition presents significant mechanical, physical and social day-to-day limitations for the quality of life of these patients. Surgical techniques are indicated for the reconstruction of the body shape and therapy of the above named problems and the coexistent psychosocial component. These surgical techniques involve dermolipectomies in different body areas and can lead to significant improvement. In view of the worldwide increase of adipositas and the increasing need for bariatric surgery, a parallel increase in demand for such reconstructive post-bariatric interventions can be foreseen. Early and precise information is crucial for the patients before engaging in weight reduction, as is the coverage of the costs of the resulting secondary reconstructive body contouring interventions by the insurance companies.

Topical application of 17ß-estradiol (E2) improves skin flap survival through activation of endothelial nitric oxide synthase in rats.

This study investigates the influence of 17ß-estradiol (E2) on nitric oxide (NO) production in endothelial cell cultures and the effect of topical E2 on the survival of skin flap transplants in a rat model. Human umbilical vein endothelial cells were treated with three different E2 concentrations and nitrite (NO2) concentrations, as well as endothelial nitric oxide synthase (eNOS) protein expressions were analyzed. In vivo, random-pattern skin flaps were raised in female Wistar rats 14 days following ovariectomy and treated with placebo ointment (group 1), E2 as gel (group 2), and E2 via plaster (group 3). Flap perfusion, survival, and NO2 levels were measured on postoperative day 7. In vitro, E2 treatment increased NO2 concentration in cell supernatant and eNOS expression in cell lysates (p < 0.05). In vivo, E2 treated (gel and plaster groups) demonstrated significantly increased skin flap survival compared to the placebo group (p < 0.05). E2 plaster-treated animals exhibited higher NO2 blood levels than placebo (p < 0.05) paralleling the in vitro observations. E2 increases NO production in endothelial cells via eNOS activation. Topical E2 application can significantly increase survival of ischemically challenged skin flaps in a rat model and may augment wound healing in other ischemic situations via activation of NO production.

Reconstruction of large supra-eyebrow and forehead defects using the hatchet flap principle and sparing sensory nerve branches.

BACKGROUND: To reconstruct a forehead defect, a plastic surgeon must be knowledgeable about the neural, vascular, and muscular anatomy. The position of fixed structures such as eyebrows and hairline should be respected. For the past 5 years, we have used double hatchet flaps for reconstruction of relatively large supra-eyebrow and forehead defects. Because this flap does not appear to be among the techniques used by young plastic surgeons, we thought that it would be valuable to report our experience. METHODS: Supra-eyebrow and forehead defects ranging from 2.5 × 2.5 cm to 3.5 × 3.5 cm were reconstructed using double hatchet flaps in 10 patients. Pearls and pitfalls of the technique are discussed along with the presentation of 3 cases. RESULTS: The reconstructions were uneventful and the flaps were highly viable in all patients. There was no significant distortion in the eyebrow or hairline due to reconstruction in any of the patients. All the flaps were sensate. A mild anesthesia in the distribution of supraorbital/trochlear nerve proximal to the flaps was noted only in 3 patients. This was associated with inevitable nerve damage during excision of malignant skin lesions and/or flap dissection. No recurrence was noted during the follow-up period which ranged from 6 to 36 months (mean, 13.5 months). Overall patient satisfaction score based on scar appearance and perceived degree of forehead anesthesia was 3 (neither satisfied nor dissatisfied) in 1 patient, was 4 (somewhat satisfied) in 4 patients, and was 5 (very satisfied) in 5 patients. CONCLUSION: Hatchet flaps have similar color and texture to that of the adjacent supra-eyebrow and forehead defects. The scarring is acceptable with reliable and reproducible results. Oftentimes, sensory nerve branches can be preserved with careful planning and tedious dissection. This type of reconstruction should be considered in the armamentarium of supra-eyebrow and forehead defects.

Incorporation of a preexisting scar in the star-flap technique for nipple reconstruction.

BACKGROUND: This report describes the authors' currently favored method of nipple reconstruction in cases of a pre-existing scar on the breast mound that passes through the intended site of nipple reconstruction. METHODS: The star flap technique incorporating a previous scar is used at least 3 months after satisfactory implant-based breast reconstruction. If the intended site of nipple reconstruction bisects through a vertical mastectomy scar, the star flap is designed as medially or laterally based with its 2 lateral limbs lying adjacent to the scar and the transverse central component incorporating the vertical scar. On the other hand, if the selected site of nipple reconstruction passes into a horizontal scar, the flap is positioned as inferiorly or superiorly based along the scar with its 2 lateral limbs adjacent to the scar and vertical central limb including the scar. Upon ensuring viability, the limbs are inset for nipple reconstruction. The flap donor wounds of the lateral limbs are closed primarily along the previous scar, and all of the scars including that of the central limb are maintained within the area of the intended areola. RESULTS: The procedure was used 16 times in 24 patients who have undergone bilateral implant-based breast reconstruction. All flaps were viable. One nipple reconstruction had an early complication of partial flap loss in the central flap that subsequently healed with wound care. CONCLUSIONS: It is possible to use a mastectomy scar in the star flap design for nipple reconstruction with no significant vascular compromise. This novel design enables positioning of the nipple in an optimal location on the breast mound in relation with the scar, use of existing scar, and inclusion of extra skin and subcutaneous tissue within the central limb. Nipple projection and volume have been satisfactory and consistently maintained.

The role of androgens on hypoxia-inducible factor (HIF)-1α-induced angiogenesis and on the survival of ischemically challenged skin flaps in a rat model.

BACKGROUND: Effects of androgens on angiogenesis are controversial. Hypoxia-inducible factor (HIF)-1α promotes expression of vascular endothelial growth factor (VEGF) that stimulates angiogenesis. PURPOSE: This study investigates whether androgens stabilize HIF-1α in endothelial cells, and androgen depletion decreases VEGF concentrations and skin flap survival. MATERIALS AND METHODS: Male human umbilical vein endothelial cells (HUVECs) were exposed to dihydrotestosterone (DHT) and HIF-1α expression was measured. In male Wistar rats, standardized proximally based random pattern dorsal skin flaps (3 × 9 cm) were raised 4 weeks after orchiectomy and sham operation, respectively (n = 10, each). Flap VEGF concentrations (immunohistochemistry), perfusion (Laser Doppler), and viability (digital planimetry) were measured. RESULTS: DHT induced HIF-1α expression in HUVECs. Androgen depletion induced decreased VEGF expression (P = 0.003), flap perfusion (P < 0.05), and survival (44.4% ± 5.2%) compared to controls (35.5% ± 4.5%; P = 0.003). CONCLUSION: In vitro, androgens may stimulate HIF-1α under normoxic conditions. In rats, androgen depletion decrease VEGF expression and flap survival.

Effective wound closure with a new two-component wound closure device (Prineo™) in excisional body-contouring surgery: experience in over 200 procedures.

BACKGROUND: In excisional body-contouring surgery the surgeon is often confronted with time-consuming closure of long wounds. Recently, a new combination of a self-adhering mesh together with a liquid 2-octyl cyanoacrylate adhesive (Prineo™; Ethicon, Inc., Somerville, NJ, USA) has been introduced to replace intracutaneous running suture. METHODS: An observational study was undertaken to evaluate the efficacy of the new wound closure device in excisional body-contouring procedures between January 2008 and November 2010. Wound characteristics were recorded in a prospectively maintained database. RESULTS: During the study period, 224 procedures in 180 patients were undertaken. Twenty-seven patients had two subsequent operations and four patients had three subsequent operations. Application of the new device was easy and safe and patient satisfaction with the results was generally high. However, intense local allergic reactions were seen in 4 patients (1.8%), which necessitated early removal and topical corticosteroid treatment. CONCLUSIONS: Prineo™ enables the surgeon to perform a quick and smooth skin closure, especially in long incisions frequently encountered in excisional body-contouring surgery. The application is fast and easy if basic guidelines are respected. Operating time is saved by eliminating the need for time-consuming intracutaneous running sutures. Removal is easy and painless for the patient. However, there is a potential for local allergic adverse effects of which the surgeon must be aware.

Efficacy of Combined in-vivo Electroporation-Mediated Gene Transfer of VEGF, HGF, and IL-10 on Skin Flap Survival, Monitored by Label-Free Optical Imaging: A Feasibility Study.

Preventing surgical flaps necrosis remains challenging. Laser Doppler imaging and ultrasound can monitor blood flow in flap regions, but they do not directly measure the cellular response to ischemia. The study aimed to investigate the efficacy of synergistic in-vivo electroporation-mediated gene transfer of interleukin 10 (IL-10) with either hepatocyte growth factor (HGF) or vascular endothelial growth factor (VEGF) on the survival of a modified McFarlane flap, and to evaluate the effect of the treatment on cell metabolism, using label-free fluorescence lifetime imaging. Fifteen male Wistar rats (290-320 g) were randomly divided in three groups: group-A (control group) underwent surgery and received no gene transfer. Group-B received electroporation mediated hIL-10 gene delivery 24 h before and VEGF gene delivery 24 h after surgery. Group-C received electroporation mediated hIL-10 gene delivery 24 h before and hHGF gene delivery 24 h after surgery. The animals were assessed clinically and histologically. In addition, label-free fluorescence lifetime imaging was performed on the flap. Synergistic electroporation mediated gene delivery significantly decreased flap necrosis (P = 0.0079) and increased mean vessel density (P = 0.0079) in treatment groups B and C compared to control group-A. NADH fluorescence lifetime analysis indicated an increase in oxidative phosphorylation in the epidermis of the group-B (P = 0.039) relative to controls. These findings suggested synergistic in-vivo electroporation-mediated gene transfer as a promising therapeutic approach to enhance viability and vascularity of skin flap. Furthermore, the study showed that combinational gene therapy promoted an increase in tissue perfusion and a relative increase in oxidative metabolism within the epithelium.

Application of electrochemotherapy in the management of primary and metastatic cutaneous malignant tumours: a systematic review and meta-analysis.

Electrochemotherapy is becoming a promising technique for the management of malignancies of skin and non-skin origin. The current review aims to clarify current knowledge on administration of electrochemotherapy for the treatment of various skin tumours. A systematic literature search was performed, up to the end of 2016, on studies in which the application of electrochemotherapy for management of primary and metastatic cutaneous malignant tumours was assessed. Having selected appropriate studies, pooled estimates of mean objective (complete) responses, with 95% confidence intervals (CIs), were calculated to assess treatment efficacy. Finally, the main emerging themes from the papers were discussed in more detail. From 465 records identified through database searching, a total of 128 studies were screened, of which 70 were included for review. After a pooled analysis, the estimate for mean objective response following electrochemotherapy was 84.02% (95% CI: 80.08-87.61). Furthermore, the pooled estimate of objective treatment response of evaluated studies was 83.91% (95% CI: 79.15-88.17%) for bleomycin and 80.82% (95% CI: 66.00-92.36%) for cisplatin. Electrochemotherapy is a feasible, inexpensive, fast and easy technique to perform local treatment, regardless of tumour type, with a low level of adverse effects and patient discomfort. This method can be applied alone for patients with primary cutaneous lesions, or local or locoregional metastases, or as an additional treatment modality in patients with distant metastases.

Correlation of Vascular Endothelial Growth Factor subtypes and their receptors with melanoma progression: A next-generation Tissue Microarray (ngTMA) automated analysis.

INTRODUCTION: Finding new markers to assess prognosis of melanoma without the necessity to perform a surgical interventions is an important goal in melanoma research. The current study aimed to assess the correlation of clinical course and prognosis of primary and metastatic melanoma with expression of VEGF family and their receptors. METHODS: A ngTMA block was made from the randomly selected paraffin tissue blocks of the patients with melanocytic nevi, primary and metastatic melanoma. Then sections cut from ngTMA-block were immunohistochemically stained with proper antibodies. Expression of these proteins was investigated using automated image analysis and compared among the study groups. RESULTS: We analyzed the tissue of 238 patients with following diagnoses: 101 (42.4%) with a diagnosis of nevus, 86 (36.1%) Malignant melanoma and 51 (21.4%) metastasis. Median follow-up time for the malignant lesions was 5.71 years. Among the tested antigen, VEGF-C (p = 0.016), VEGF-R2 (p<0.001) and VEGF-R3 (p = 0.002) were significantly higher expressed in the metastatic tissues. When these scores were assessed in multiple regression models, the only independent factor linked to patient's diagnosis was VEGF-R2 (p<0.001). In addition, groups of highly correlated variables (VEGF-C and VEGF-R3, VEGF-A and VEGF-R1) were found to form separate sub-clusters. On the other side, high values of VEGF-C were associated with both overall and disease-free survival with a statically significant HR of 2.76 (95% CI: 1.27, 5.98; p = 0.01) and 2.82 (95%CI: 1.62, 4.91; p<0.001), respectively. CONCLUSIONS: This study shows that VEGF-C and VEGF-R2 might represent new prognostic marker in MM. However, further prospective studies are warranted to test their real efficacy as a prognostic marker.

Improvement of Flap Necrosis in a Rat Random Skin Flap Model by In Vivo Electroporation-Mediated HGF Gene Transfer.

BACKGROUND: Despite great understanding of underlying mechanisms for flap necrosis and advances in surgical techniques, flap necrosis remains a critical issue. In the present study, the authors investigated the efficacy of electroporation-mediated hepatocyte growth factor (HGF) gene delivery to random dorsal skin flaps (McFarlane) to accelerate wound healing and reduce flap necrosis. METHODS: Fifteen male Wistar rats (290 to 320 g) were divided randomly into three groups. Group a, the control group (n = 5), underwent surgery and received no gene transfer. Group b received electroporation-mediated HGF gene delivery 24 hours after surgery as a treatment. Group c received electroporation-mediated HGF gene delivery 24 hours before surgery as prophylaxis (n = 5). Planimetry, laser Doppler imaging, and immunohistochemistry were used to assess the efficacy of HGF gene therapy among the groups. RESULTS: Electroporation-mediated HGF gene delivery significantly decreased flap necrosis percentage compared with the control group in prophylactic and treatment groups (p = 0.0317 and p = 0.0079, respectively) and significantly increased cutaneous perfusion compared with the control group (p = 0.0317 and p = 0.0159, respectively). Moreover, Spearman rank correlation showed a significant negative correlation between flap necrosis percentage and laser index (p = 0.0213 and r = -0.5964, respectively). Furthermore, significantly higher mean CD31 vessel density was detected in treatment and prophylactic groups (p = 0.0079 and p = 0.0159, respectively). In addition, quantitative image analysis revealed significantly higher HGF protein expression in groups b and c (p = 0.0079 and p = 0.0079, respectively). CONCLUSION: These findings suggested in vivo electroporation-mediated HGF gene delivery enhanced viability and vascularity of the ischemic skin flap.

New approach for virtual surgical planning and mandibular reconstruction using a fibula free flap.

Maxillofacial reconstruction poses a major challenge to surgeons because of the associated anatomical complexity, the sensitivity of the involved systems and the need to maintain a pleasing facial appearance. Here, we present a detailed description of a new method for extensive mandibular reconstruction using open-source virtual design software and a desktop 3D printer. A surgeon segmented preoperative computed tomography angiography scans with the Amira program to create a digital model of the mandible, skull and fibula. These datasets were imported into Blender, an open-source computer-aided design software package, where arrangement of the fibula segments into aligned sections was performed. Then, a desktop 3D printer was used to produce a reconstructed mandible. After fixation of a plate onto the reconstructed mandible, cutting guides were digitally designed using Blender. Following this, the surgeon performed mandible resection using the fixed cutting guides, which were 3D-printed using biocompatible plastic (Med 610/Stratasys Inc.) and fixed to the prebent reconstructed mandible at a predetermined position. After cutting the fibula with the help of the cutting guides and aligning the fibular segments into mandibular space, the surgeon fixed the segments to the reconstruction plate. Postoperatively, multislice computed tomography scans were taken for control purposes. Our method for mandibular reconstruction offers the following benefits: shorter operation planning time, increased accuracy during osteotomy through the use of a special fibula cutting guide and low costs. In brief, this method is an easy, precise and highly flexible technique for mandibular reconstruction with a fibula flap.