Sinking skin flap syndrome with delayed dysautonomic syndrome - An atypical presentation

INTRODUCTION Sinking skin flap syndrome or syndrome of the trephined is a rare complication after a large craniectomy, with a sunken skin above the bone defect with neurological symptoms such as severe headache, mental changes, focal deficits, or seizures. PRESENTATION OF CASE We report a case of 21 years old man with trefinated syndrome showing delayed dysautonomic changes. DISCUSSION Our patient had a large bone flap defect and a VP shunt that constitute risk factors to develop this syndrome. Also, there is reabsorption of bone tissue while it is placed in subcutaneous tissue. The principal symptoms of sinking skin flap syndrome are severe headache, mental changes, focal deficits, or seizures. Our patient presented with a delayed dysautonomic syndrome, with signs and symptoms very characteristics. Only few cases of this syndrome were related in literature and none were presented with dysautonomic syndrome. CONCLUSION We reported here a very uncommon case of sinking skill flap syndrome that causes a severe dysautonomic syndrome and worsening the patient condition. © 2013 The Authors.

LED (660 nm) and laser (670 nm) use on skin flap viability: angiogenesis and mast cells on transition line

Skin flap procedures are commonly used in plastic surgery. Failures can follow, leading to the necrosis of the flap. Therefore, many studies use LLLT to improve flap viability. Currently, the LED has been introduced as an alternative to LLLT. the objective of this study was to evaluate the effect of LLLT and LED on the viability of random skin flaps in rats. Forty-eight rats were divided into four groups, and a random skin flap (10 x 4 cm) was performed in all animals. Group 1 was the sham group; group 2 was submitted to LLLT 660 nm, 0.14 J; group 3 with LED 630 nm, 2.49 J, and group 4 with LLLT 660 nm, with 2.49 J. Irradiation was applied after surgery and repeated on the four subsequent days. On the 7th postoperative day, the percentage of flap necrosis was calculated and skin samples were collected from the viable area and from the transition line of the flap to evaluate blood vessels and mast cells. the percentage of necrosis was significantly lower in groups 3 and 4 compared to groups 1 and 2. Concerning blood vessels and mast cell numbers, only the animals in group 3 showed significant increase compared to group 1 in the skin sample of the transition line. LED and LLLT with the same total energies were effective in increasing viability of random skin flaps. LED was more effective in increasing the number of mast cells and blood vessels in the transition line of random skin flaps.

Low-level laser therapy (670 nm) on viability of random skin flap in rats

This study investigated the effects of 670 nm laser, at different fluences, on the viability of skin flap in rats. One hundred male animals were used. The animals were divided into control group; group treated with 3 J/cm(2); group treated with 6 J/cm(2); group treated with 12 J/cm(2) and group treated with 24 J/cm(2). The skin flap was made on the backs of all animals studied, with a plastic sheet interposed between the flap and the donor site. Laser irradiation was done immediately after the surgery and on days 1, 2, 3 and 4 after surgery. The percentage of necrosis of the flap was calculated at the 7th postoperative day. Additionally, a sample of each flap was collected to enable us to count the blood vessels. Treated animals showed a statistically significant smaller area of necrosis than did the control group. The necrosis in the treated groups was 41.82% (group 2), 36.51% (group 3), 29.45% (group 4) and 20.37% (group 5). We also demonstrated that laser irradiation at 670 nm, at all doses used, had a stimulatory effect on angiogenesis. Our study showed that the 670 nm laser was efficient to increase the viability of the skin flap, at all fluences used, with a tendency of reaching better results at higher doses.

Low level laser therapy increases angiogenesis in a model of ischemic skin flap in rats mediated by VEGF, HIF-1α and MMP-2

It is known that low level laser therapy is able to improve skin flap viability by increasing angiogenesis. However, the mechanism for new blood vessel formation is not completely understood. Here, we investigated the effects of 660 nm and 780 nm lasers at fluences of 30 and 40 J/cm2 on three important mediators activated during angiogenesis. Sixty male Wistar rats were used and randomly divided into five groups with twelve animals each. Groups were distributed as follows: skin flap surgery non-irradiated group as a control; skin flap surgery irradiated with 660 nm laser at a fluence of 30 or 40 J/cm2 and skin flap surgery irradiated with 780 nm laser at a fluence of 30 or 40 J/cm2. The random skin flap was performed measuring 10 × 4 cm, with a plastic sheet interposed between the flap and the donor site. Laser irradiation was performed on 24 points covering the flap and surrounding skin immediately after the surgery and for 7 consecutive days thereafter. Tissues were collected, and the number of vessels, angiogenesis markers (vascular endothelial growth factor, VEGF and hypoxia inducible factor, HIF-1α) and a tissue remodeling marker (matrix metalloproteinase, MMP-2) were analyzed. LLLT increased an angiogenesis, HIF-1α and VEGF expression and decrease MMP-2 activity. These phenomena were dependent on the fluences, and wavelengths used. In this study we showed that LLLT may improve the healing of skin flaps by enhancing the amount of new vessels formed in the tissue. Both 660 nm and 780 nm lasers were able to modulate VEGF secretion, MMP-2 activity and HIF-1α expression in a dose dependent manner. © 2013 Published by Elsevier B.V.

Effects of 830 and 670 nm Laser on Viability of Random Skin Flap in Rats

Objective: This study aimed to investigate the effect of 830 and 670 nm diode laser on the viability of random skin flaps in rats. Background data: Low-level laser therapy (LLLT) has been reported to be successful in stimulating the formation of new blood vessels and reducing the inflammatory process after injury. However, the efficiency of such treatment remains uncertain, and there is also some controversy regarding the efficacy of different wavelengths currently on the market. Materials and methods: Thirty Wistar rats were used and divided into three groups, with 10 rats in each. A random skin flap was raised on the dorsum of each animal. Group 1 was the control group, group 2 received 830 nm laser radiations, and group 3 was submitted to 670 nm laser radiation (power density = 0.5 mW/cm(2)). The animals underwent laser therapy with 36 J/cm(2) energy density (total energy = 2.52 J and 72 sec per session) immediately after surgery and on the 4 subsequent days. The application site of laser radiation was one point at 2.5 cm from the flap's cranial base. The percentage of skin flap necrosis area was calculated on the 7th postoperative day using the paper template method. A skin sample was collected immediately after to determine the vascular endothelial growth factor (VEGF) expression and the epidermal cell proliferation index (KiD67). Results: Statistically significant differences were found among the percentages of necrosis, with higher values observed in group 1 compared with groups 2 and 3. No statistically significant differences were found among these groups using the paper template method. Group 3 presented the highest mean number of blood vessels expressing VEGF and of cells in the proliferative phase when compared with groups 1 and 2. Conclusions: LLLT was effective in increasing random skin flap viability in rats. The 670 nm laser presented more satisfactory results than the 830 nm laser.

Dimethyloxalylglycine stabilizes HIF-1α in cultured human endothelial cells and increases random-pattern skin flap survival in vivo

The goal of this study was to evaluate in vitro and in vivo the effects of up-regulation of the proangiogenic hypoxia inducible factor (HIF)-1α induced by dimethyloxalylglycine on endothelial cell cultures and on skin flap survival.

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

This study investigates the influence of 17β-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.

Gene therapy with adenovirus-mediated VEGF enhances skin flap prefabrication

We investigated the feasibility in rats of enhancing skin-flap prefabrication with subdermal injections of adenovirus-encoding vascular endothelial growth factor (Ad-VEGF). The left saphenous vascular pedicle was used as a source for vascular induction. A peninsular abdominal flap (8 x 8 cm) was elevated as distally based, keeping the epigastric vessels intact on both sides. After the vascular pedicle was tacked underneath the abdominal flap, 34 rats were randomly divided into three groups according to treatment protocol. The implantation site around the pedicle was injected with Ad-VEGF in group I (n = 10), with adenovirus-encoding green fluorescent protein (Ad-GFP) in control group I (n = 14), and with saline in control group II (n = 10). All injections were given subdermally at four points around the implanted vessel by an individual blinded to the treatment protocol. The peninsular flap was sutured in its place, and 4 weeks later, an abdominal island flap based solely on the implanted vessels was elevated. The prefabricated island flap was sutured back, and flap viability was evaluated on day 7. Skin specimens were stained with hematoxylin and eosin for histological evaluation. In two rats from each group, microangiography was performed to visualize the vascularity of the prefabricated flaps. There was a significant increase in survival of prefabricated flaps in the Ad-VEGF group compared to the control groups: Ad-VEGF, 88.9 +/- 6.1% vs. Ad-GFP, 65.6 +/- 9.4% (P < 0.05) and saline, 56.0 +/- 3.4% (P < 0.05). Sections from four prefabricated flaps treated with Ad-GFP revealed multiple sites of shiny deposits of green fluorescent protein around the area of local administration 1 day and 3 weeks after gene therapy. Histological examination done under high-power magnification (x400) with a light microscope revealed increased vascularity and mild inflammation surrounding the implanted vessel in all groups. However, we were unable to demonstrate any significant quantitative difference with respect to vascularity and inflammatory infiltrates in prefabricated flaps treated with Ad-VEGF compared with controls. Microangiographic studies showed increased vascularity around the implanted pedicle, which was similar in all groups. However, vascularization was distributed in a larger area in the prefabricated flaps treated with Ad-VEGF. In this study, the authors demonstrated that adenovirus-mediated VEGF gene therapy increased the survival of prefabricated flaps, suggesting that it may allow prefabrication of larger flaps and have the potential to reduce the time required for flap maturation.

Initial characterization of stiff skin-like syndrome in West Highland white terriers

BACKGROUND Stiff skin syndrome and systemic or localized scleroderma are cutaneous disorders characterized by dermal fibrosis and present clinically with induration of the skin, with or without joint, internal organ or vascular involvement. OBJECTIVES To provide clinical, histological and preliminary genetic analysis of two West Highland white terrier siblings presenting with indurated skin resembling stiff skin syndrome in humans. ANIMALS Two client owned full sibling West Highland white terriers from two different litters. METHODS Clinical examination, histopathological examination and whole genome sequencing analysis of affected and unaffected West Highland white terriers. RESULTS Affected dogs exhibited markedly indurated skin that was attached firmly to the underlying tissue and incomplete closure of the mouth and eyes. No abnormalities were found by neurological or orthopaedic examination, radiographs of the head or whole body computed tomography. Histologically, the dermis and pannicular septa were thickened by a marked increase in coarse collagen fibres and a mild to moderate increase in collagen fibre diameter. The syndrome most likely follows an autosomal recessive mode of inheritance. The sequence analysis did not reveal any obvious causative variant in the investigated candidate genes ADAMTSL2 and FBN1. CONCLUSION AND CLINICAL IMPORTANCE The clinical phenotype and histopathological features of two West Highland white terrier siblings resembled stiff skin syndrome in humans. Unlike in humans, or previously described beagles with stiff skin, there was no restriction of joint mobility. Genetic analysis did not detect a candidate causative variant and warrants further research.

Skin-reducing mastectomy and one-stage implant reconstruction with a myodermal flap: A safe and effective technique in risk-reducing and therapeutic mastectomy

Introduction: Immediate reconstruction following mastectomy for breast cancer has been shown to be oncologically safe and associated with improved psychosocial outcomes for patients. Bostwick described a technique for one-stage implant based reconstruction, combining skin-sparing mastectomy with concurrent reduction of the skin envelope. This report reviews the experience of a single centre using skin-reducing mastectomy and one-stage implant reconstruction in both early stage breast cancer and risk-reducing mastectomy, with specific reference to frequency of complications, implant loss and oncological outcomes.

Methods and results: A retrospective review was undertaken to identify women who had undergone skin-reducing mastectomy and one-stage implant reconstruction using a de-epithelialised dermal flap, between October 2008 and October 2012. One hundred and four consecutive mastectomies, with reconstruction, were performed by two surgeons on 64 patients. No complications were seen in 43.8% of patients. At three months, four implants were lost (3.8% of breast reconstructions, 6.3% of patients), due to either peri-implant infection or mastectomy skin flap necrosis. One patient required unplanned return to theatre for evacuation of a haematoma. Minor mastectomy skin flap necrosis was seen in 10 breasts (9.6% of reconstructed breasts) and superficial wound infection in 8 breasts (7.7% of reconstructed breasts). All of these complications were managed conservatively and none required operative intervention. At a median follow up of 35 months (4-53 months) there had been one episode of ipsilateral axillary nodal recurrence.

Conclusion: One-stage implant reconstruction using a myo-dermal flap technique following skin-reducing mastectomy is safe and should be considered in selected patients. Most complications are minor and will resolve with conservative management. Major complications such as implant failure or immediate reoperation, were relatively uncommon (6.3% patients, 3.8% of reconstructed breasts). Early follow-up suggests that oncological outcomes are satisfactory, but longer follow-up is required to substantiate this. (C) 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Ischemia and reperfusion in skin flaps: effects of mannitol and vitamin C in reducing necrosis area in a rat experimental model

OBJETIVO: Neste trabalho foi padronizado modelo experimental de isquemia e reperfusão em retalho cutâneo em ratos no qual estudou-se possibilidade de uma solução antioxidante, composta por Ringer lactato, vitamina C e manitol de reduzir a área de necrose. MÉTODOS: O modelo consistiu de levantamento de retalho cutâneo axial de 6,0 x 3,0cm, submetido à isquemia de 8 horas e reperfusão de 7 dias. Os animais foram divididos em quatro grupos: grupos S1, S2 (10 animais cada), C e T (14 animais cada). Nos grupos S1 e S2 todos os procedimentos dos demais grupos foram efetuados, exceto a isquemia e reperfusão: S1 recebeu apenas Ringer lactato e S2 a solução antioxidante. Os grupos C e T foram submetidos à isquemia. O grupo C recebeu somente Ringer lactato e o grupo T a solução antioxidante. No 7(0) dia de pós-operatório as áreas de necrose e pele viável do retalho foram delineadas em decalque de acetato, os quais foram por sua vez analisados em sistema computadorizado KS-300 (Carl Zeiss). RESULTADOS: A análise estatística mostrou que não houve diferenças significativas entre o grupo tratado e controle quanto à área de necrose. CONCLUSÃO: Concluiu-se que o modelo experimental é consistente, determinando área de necrose limitada e uniforme nos animais não tratados e que as drogas usadas, nessa posologia e modo de aplicação, não foram efetivas em diminuir a área de necrose no modelo experimental em questão.

Magnesium sulphate given topically by iontophoresis for viability of random skin flaps in rats

Our aim was to assess the effects of magnesium sulphate given by iontophoresis on the viability of random skin flaps in rats. Endovenous magnesium sulphate is used to treat pre-eclampsia and diseases of blood vessels. Iontophoresis is an electrotherapeutic method which has shown satisfactory results in controlling ischaemia within the boundaries of the area in which it was given. Forty-five adult male Wistar rats, weighing 300 to 440 g were randomly divided into three groups of 15 animals each: random skin flap (control); random skin flap treated with magnesium sulphate without electrical stimulation; and random skin flap treated with magnesium sulphate with electrical stimulation of 4 mA for 20 minutes. The treatments were applied immediately after the operation and repeated on the following two days. The percentage of necrotic area was measured on the seventh postoperative day using a paper template. For each group, the mean percentage of flap necrosis was as follows: control, 46%; magnesium sulphate without electrical stimulation, 34%; and magnesium sulphate with electrical stimulation, 42%. There was no significant difference among the groups (p=0.18). Magnesium sulphate given by iontophoresis does not increase the viability of random skin flaps in rats.

The choice of anesthesia influences oxidative energy metabolism and tissue survival in critically ischemic murine skin

In surgical animal studies anesthesia is used regularly. Several reports in the literature demonstrate respiratory and cardiovascular side effects of anesthesiologic agents. The aim of this study was to compare two frequently used anesthesia cocktails (ketamine/xylazine [KX] versus medetomidine/climazolam/fentanyl [MCF]) in skin flap mouse models. Systemic blood values, local metabolic parameters, and surgical outcome should be analyzed in critical ischemic skin flap models. Systemic hypoxia was found in the animals undergoing KX anesthesia compared with normoxia in the MCF group (sO(2): 89.2% +/- 2.4% versus 98.5% +/- 1.2%, P < 0.01). Analysis of tissue metabolism revealed impaired anaerobic oxygen metabolism and increased cellular damage in critical ischemic flap tissue under KX anesthesia (lactate/pyruvate ratio: KX 349.86 +/- 282.38 versus MCF 64.53 +/- 18.63; P < 0.01 and glycerol: KX 333.50 +/- 83.91 micromol/L versus MCF 195.83 +/- 29.49 micromol/L; P < 0.01). After 6 d, different rates of flap tissue necrosis could be detected (MCF 57% +/- 6% versus KX 68% +/- 6%, P < 0.01). In summary we want to point out that the type of anesthesia, the animal model and the goal of the study have to be well correlated. Comparing the effects of KX and MCF anesthesia in mice on surgical outcome was a novel aspect of our study.

Paracrine effects of mesenchymal stem cells enhance vascular regeneration in ischemic murine skin

New theories on the regeneration of ischemic vasculature have emerged indicating a pivotal role of adult stem cells. The aim of this study was to investigate homing and hemodynamic effects of circulating bone marrow-derived mesenchymal stem cells (MSCs) in a critically ischemic murine skin flap model. Bone marrow-derived mesenchymal stem cells (Lin(-)CD105(+)) were harvested from GFP(+)-donor mice and transferred to wildtype C57BL/6 mice. Animals receiving GFP(+)-fibroblasts served as a control group. Laser scanning confocal microscopy and intravital fluorescence microscopy were used for morphological analysis, monitoring and quantitative assessment of the stem cell homing and microhemodynamics over two weeks. Immunohistochemical staining was performed for GFP, eNOS, iNOS, VEGF. Tissue viability was analyzed by TUNEL-assay. We were able to visualize perivascular homing of MSCs in vivo. After 4 days, MSCs aligned along the vascular wall without undergoing endothelial or smooth muscle cell differentiation during the observation period. The gradual increase in arterial vascular resistance observed in the control group was abolished after MSC administration (P<0.01). At capillary level, a strong angiogenic response was found from day 7 onwards. Functional capillary density was raised in the MSC group to 197% compared to 132% in the control group (P<0.01). Paracrine expression of VEGF and iNOS, but not eNOS could be shown in the MSC group but not in the controls. In conclusion, we demonstrated that circulating bone marrow-derived MSCs home to perivascular sites in critically ischemic tissue, exhibits paracrine function and augment microhemodynamics. These effects were mediated through arteriogenesis and angiogenesis, which contributed to vascular regeneration.