Dorsal Skin Flap Research Articles

Effects of Apigenin Treatment on Random Skin Flap Survival in Rats.

Random skin flaps are often used in plastic surgery, but the complications of marginal flap ischemia and necrosis often limit their wider clinical application. Apigenin (Api) is a flavonoid found in various fruits and vegetables. Api has been shown to promote angiogenesis, as well as reduce oxidative stress, membrane damage, and inflammation. In this study, we assessed the effects of Api treatment on random skin flap survival. Dorsal McFarlane skin flaps were transplanted into rats, which were randomly divided into three groups: control (normal saline), low-dose Api (20 mg/kg), and high-dose Api (50 mg/kg). Seven days after the surgery, the activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were measured. Histological analyses were performed to determine flap survival and tissue edema. H&E staining was performed to assess the histopathological changes in skin flaps, and the levels of microvascular density (MVD) were determined. Laser doppler flowmetry was used to assess microcirculation blood flow. Flap angiography was performed by injection of lead oxide/gelatin. The expression levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interlukin-1β (IL-lβ) were evaluated by immunohistochemistry. Rats in the high-dose Api group exhibited higher average flap survival area, microcirculatory flow, increased SOD activity, and higher VEGF expression levels compared with the other two groups. Furthermore, the levels of MDA and pro-inflammatory cytokines were significantly decreased in rats treated with high-dose Api. Our findings suggest the potential usefulness of Api in preventing skin flap tissue necrosis.

Enhancement the skin flap survival in mice applying topical and systemic atorvastatine:a randomized clinical trial study

IntroductionSkin flaps play a valuable role in reconstructive surgeries⋅ However, ischemia and necrosis of random designed flaps are still a challenging entity. Our objective was to investigate the feasibility of atorvastatin applied in topical and systemic form to improve the skin flap survival in mice. Materials and methodOne hundred adult male mice of the same strain were randomly divided into four main groups. After anesthesia and prophylactic antibiotic injection, random dorsal skin flaps were designed based on the modified McFarlane's method. In the first main group (control group) which contains two subgroups saline was administered intraperitonealy and topically respectively. In the second main group (vehicle group) carboxymethyl cellulose(vehicle solution) was administered intraperitonealy in one subgroup and vaseline applied topically in the other subgroup. In the third main groups (included three subgroups) 1, 5, and 10mgr/kg of body weight atorvastatin dissolved in carboxymethyl cellulose applied intraperitonealy for two weeks. In the fourth group (included three subgroups) atorvastatin ointment 1%, 5%, and 10% was applied topically for 14 days. After 2 weeks flap necrotized surface investigated using digital photography. ResultsAtorvastatin in Systemic and topical form could decrease the necrotic surface of the random designed skin flap. However, systemic application of atorvastatin seems to be more effective than topical administration, No statistically significant difference was observed between low dose atorvastatin (1 and 5 mg/kg).

Effect of hyperbaric oxygenation on random rat skin flaps vascularization.

ABSTRACTPurpose:To evaluate the effect of hyperbaric oxygenation (HBO) on angiogenesis in random rat skin flaps, by immunoexpression of vascular endothelial growth factor A (VEGF-A).Methods:Forty adult rats were divided into four groups: GE) epilated; GE/HBO) epilated subjected to HBO; GER) epilated submitted to dorsal skin flap; GER/HBO) epilated subjected to dorsal skin flap + HBO. HBO was performed with rats inside a chamber under atmosphere close to 100% oxygen and pressure of 2.4 absolute atmospheres, 2h per day during seven consecutive days. GE and GER groups were placed in the hyperbaric chamber without HBO. Then, under anesthesia, skin flaps were removed and separated into three portions relative to pedicle fixation. The samples were fixed in formalin and processed for paraffin embedding. Histological sections were submitted to immunohistochemistry for VEGF-A detection. The number of immunostained-blood vessels were counted under light microscopy.Results:GE and GE/HBO groups showed normal and similar skin morphology in the three flap portions. A fibrin-leukocyte crust, along with denatured collagen and intense leukocyte infiltrate, was mainly observed in the dermis of the medial and distal flap portions of GER group. Meanwhile, the GER/HBO group presented more regions with intact collagen and small areas of leukocyte infiltrate in the three flap regions. VEGF-A-immunostained blood vessels were largely seen in all regions of GE and GE/HBO groups, whereas no significant differences were found between these groups. A decrease in vascularization was noticed in GER and GER/HBO groups, which was more evident in the most distal portion of the flaps. However, the number of VEGF-A-immunostained blood vessels in GER/HBO group was significantly higher when compared to GER group.Conclusions:Hyperbaric oxygenation was associated with increased angiogenesis and improved viability of rat skin flaps.

Effects of Atorvastatin Calcium on the Survival of Ultra-long Dorsal Random Skin Flaps in Rats

To investigate the effects of atorvastatin calcium (ATR) on the survival of ultra-long dorsal random skin flaps in rats. Thirty SD rats were divided into five groups ( n=6) according to the random number table: normal saline control group (CON group), ATR 10 mg/kg group (P10 group), ATR 20 mg/kg group (P20 group), ATR 30 mg/kg group (P30 group), and ATR 40 mg/kg group (P40 group). After pretreatment with ATR or 0.9% saline for 3 days, an ultra-long dorsal random skin flaps with size of 8 cm×2 cm was made on the back of each rat and replanted in situ. After the operation, the ATR or saline treatment lasted for 3 d. Seven days after operation, the appearance of skin flaps was observed with naked eyes, the survival rate of skin flaps was calculated. The pathological changes in the surviving areas of skin flaps were observed by HE staining, the number of microvessels in skin flaps was observed by immunohistochemistry staining, the mRNA expressions of vascular endothelial growth factor ( VEGF) and basic fibroblast growth factor ( bFGF) were tested by quantitative real-time PCR, and the contents of superoxide dismutase, nitrogen monoxide and malonaldehyde were tested by enzyme linked immunosorbent assays (ELISA). On the 7 thday after operation, the skin flap of the CON group showed a large area of necrosis, and the necrotic part formed crusts. Crusts were hard and inelastic, and a large amount of tissue fluid exudated. The fascial layer showed dark purple. No exudation of tissue fluid was observed in the flaps of P10, P20, P30 and P40 groups. The scab shell fell off naturally and the fur grew normally. HE staining of CON group showed that a large number of inflammatory cell infiltration, epidermal loss and necrosis in skin flaps, but the pathological changes in skin flaps were significantly improved after treatment with ATR. Compared with the CON group, the survival rate of skin flaps, the number of microvessels in skin flaps and the levels of VEGF mRNA, bFGF mRNA, SOD, NO in skin flaps also increased with the dose of ATR, which reached a peak at 30 mg/kg ATR ( P<0.05). However, the level of MDA in skin flaps decreased with the dose of ATR, which reached the lowest at 30 mg/kg ATR ( P<0.05). ATR can enhance the survival of ultra-long dorsal random skin flaps in rats, which may be related to promoting microangiogenesis and inhibiting inflammatory and oxidative stress.

Therapeutic Effects against Tissue Necrosis of Remote Ischemic Preconditioning Combined with Human Adipose-Derived Stem Cells in Random-Pattern Skin Flap Rat Models

Introduction Remote ischemic preconditioning (rIPC) is a preventive strategy against ischemia–reperfusion injury. To reduce ischemia–reperfusion injury of random-pattern skin flaps, we investigated the therapeutic effects of rIPC combined with human adipose-derived stem cells (hADSCs) in a rat model. Material and Methods In total, 24 female Sprague Dawley rats were divided into four groups (n = 6 each): control (skin flap only), rIPC, hADSCs, and rIPC + hADSCs. rIPC was performed in the hind limb of the rats over three cycles of 5 min of occlusion and 5 min of reperfusion, using a tourniquet. A rectangular (3 × 9 cm) dorsal skin flap was used. hADSCs (5 × 105 cells/100 µL) labeled with fluorescent dye were transplanted into the normal subcutaneous tissue at the skin flap boundary. After 14 days, the therapeutic effects of rIPC and hADSCs were evaluated via analysis of the necrotic flap area, histopathologic assessment, and immunohistochemistry (von Willebrand Factor (vWF) and CD31). Results The necrotic area of the skin flap significantly decreased in the rIPC + hADSCs group (32.75 ± 1.43%) compared with the control (40.60 ± 3.27%, P < 0.01) and rIPC groups (38.84 ± 0.77%, P < 0.05). Dye-labeled hADSCs migrated to the skin flap from the injection site. In the rIPC + hADSCs group, the epithelial tissue and skin appendage had regenerated, and the smooth muscle and subcutaneous fat layers were preserved. Many more vWF- and CD31-positive vessels were observed in the rIPC + hADSCs group compared with the other groups. Conclusions The rIPC + hADSCs treatment appeared to reduce skin flap necrosis and activated neovascularization in rats. Therefore, it may be a good strategy for clinical treatment of ischemia–reperfusion injury.

Nasal dermoid cyst excision with a lateral rhinotomy approach through the nasal alar sulcus

<i>Introduction:</i> Nasal dermoid tumors are the most common congenital midline nasal mass and develop as a result of failed involution of the neuroectomderm in the prenasal space. MRI is the diagnostic imaging study of choice. Nasal dermoids are classically treated by surgical excision. Many surgical approaches have been described including an external rhinoplasty, a lateral rhinotomy, a U-shaped or a longitudinal dorsal rhinotomy, a gull wing incision, a medial canthal incision, a nasal endoscopic resection, and a bicoronal incision. We present here a novel approach utilizing a lateral rhinotomy incision involving the nasal-alar sulcus with infratip and contralateral extension. <i>Case description:</i>We present a case of a 15-year-old male with acute swelling/tenderness to his nasal dorsum that did not resolve with 2 weeks of antibiotic therapy. Physical exam demonstrated a soft, compressible 2.5 × 2.5 cm mass on a saddled dorsum. CT and MRI imaging confirmed the presence of a nasal dermoid tumor within the anterior nose without evidence of intracranial extension. Surgical excision was performed using a novel approach to the nasal dorsum. A curvilinear incision was planned along the right nasal sidewall and continuing along the alar sulcus to the infra-tip lobule and up to the nasal alar sulcus on the left. A 4 mm punch was placed through the central pit on the lower third of the nasal dorsum along the midline axis to serve as a subcutaneous landmark during the dissection. A dorsal skin flap was elevated along the planed incision from right to left in the subcutaneous plane until reaching the punched central nasal pit. The midline dorsal mass was identified as well as the connecting stalk through the punch to the dorsal cutaneous pit. This mass was resected en bloc and was removed from the nasal cavity. Autologous rib harvest was used for nasal dorsum reconstruction. <i>Discussion:</i> When planning the surgical approach to the midline nasal mass should, the surgeon must understand that the approach taken should provide the ability to perform medial and lateral osteotomies if required, should favor rapid repair of cribiform defects with associated cerebrospinal fluid leak if present, should facilitate reconstruction of the nasal dorsum, and should offer the likely outcome of an acceptable scar. The approach described meets these requirements and provides tremendous access and visualization for resection. This approach may be considered for other prenasal soft tissue mass resections as well.

New Simple Technique for Syndactyly Release.

Background:Can good functional and cosmetic result be achieved in syndactyly separation using a straight midline incision with a hexagonal dorsal skin flap?Methods:We performed 39 web reconstructions at a median of 20 months of age (11–43 months) to 26 consecutive children (21 male) with 30 simple, 4 complex, and 5 complicated syndactylies. Eighteen of the simple syndactylies were incomplete, ending at the proximal interphalangeal joint in 15 and at the distal interphalangeal joint in 3. Inguinal skin grafts were used in 2 children with either complex or complicated syndactyly. Operation time was recorded. Complications were registered. Height of the new web spaces was calculated. Parents’ satisfaction on both functional and cosmetic outcome was assessed using a Visual Analog Scale from 0 to 100.Results:Duration of one web reconstruction ranged from 50 to 95 minutes in simple incomplete, 56 to 135 in simple complete, 116 to 151 in complex, and 72 to 123 in complicated syndactylies. One child had a self-induced bilateral postoperative infection that lead to web creep. Two patients developed hypertrophic scars, which responded well to silicone treatment. Mean cosmetic and functional Visual Analog Scale scores were 87 (45–100) and 92 (63–100), respectively, at a mean follow-up of 1.3 years (range, 0.5–3.7).Conclusion:Web reconstruction using a hexagonal dorsal skin flap and straight midline incisions with closure at mid-lateral lines is safe, with good cosmetic and functional outcome in our short-term follow-up.

Effect of dipyridamole on random pattern skin flap viability in rats

Ischemic necrosis has been most dreaded complication of flap reconstruction. Therefore, researchers have tried to improvise modalities to prevent or treat it since the onset of flap surgery. So far these researches have failed to identify a pharmacological therapy equally effective as surgical delay in augmenting skin flap viability. In the path of search for this substance, dipyridamole attracted our attention as an antiaggregant agent. Put together with pathophysiological mechanisms underlying ischemic flap necrosis, we concluded dipyridamole might have beneficial effect on survival of skin flaps. In this research random pattern dorsal rat skin flap model of McFarlane is used. Subjects are separated in a randomized fashion between two groups. Experiment group is given dipyridamole with a dose of 20 mg/kg twice daily. Control group is given same amount of saline. At seventh day viability of skin flaps is assessed and compared between groups. Also on 7th day, pathologic specimens are obtained and evaluated histopathologically in terms of neutrophil and lymphocyte infiltration, edema and fibrosis. Necrosis percentage in experiment group is found to be significantly lower than that of control group (p < 0.01*). Neutrophil infiltration and edema found to be significantly lower in dipyridamole group (p < 0.05*). No significant difference is observed in lymphocyte infiltration and fibrosis. Dipyridamole is shown in this research to be effective in augmenting viability of random pattern skin flaps in rats. Nevertheless, more extensive researches are needed to fully determine its precise mechanism, side effects and appropriate doses.

V09-11 WATCH SHAPED BUCCAL MUCOSA GRAFT FOR SIMULTANEOUS CORRECTION OF SEVERE CHORDEE AND URETHROPLASTY AS A ONE STAGE REPAIR OF SCROTAL HYPOSPADIAS

You have accessJournal of UrologyPediatrics (V09)1 Apr 2020V09-11 WATCH SHAPED BUCCAL MUCOSA GRAFT FOR SIMULTANEOUS CORRECTION OF SEVERE CHORDEE AND URETHROPLASTY AS A ONE STAGE REPAIR OF SCROTAL HYPOSPADIAS Miroslav Djordjevic*, Abdulmuttalip Simsek, Marta Bizic, Borko Stojanovic, Joshua Roth, and Rajveer Purohit Miroslav Djordjevic*Miroslav Djordjevic* More articles by this author , Abdulmuttalip SimsekAbdulmuttalip Simsek More articles by this author , Marta BizicMarta Bizic More articles by this author , Borko StojanovicBorko Stojanovic More articles by this author , Joshua RothJoshua Roth More articles by this author , and Rajveer PurohitRajveer Purohit More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000923.011AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Severe hypospadias repair still presents a great challenge. We evaluated a novel approach of using a specially shaped buccal mucosa graft for simultaneous ventral tunica grafting and new urethral plate creation in combination with a longitudinal dorsal island skin flap for a one-stage repair of severe hypospadias. METHODS: A 14-month-old boy underwent scrotal hypospadias repair. The short and non-elastic urethral plate is divided. Buccal mucosa graft is harvested from the inner cheek, and designed in a special “watch” shape, with the spherical part in the middle and two rectangular parts on both sides. The tunica albuginea is opened ventrally for penile straightening and grafted to the spherical part of the "watch-shaped" buccal mucosa with 6-8 “U-shape” stitches. The rectangular parts are fixed to the tip of the glans distally and native urethral meatus proximally. A longitudinal dorsal skin flap is harvested, button-holed ventrally and joined with the buccal graft. Penile skin reconstruction is performed using available penile skin. RESULTS: Good appearance of the penis is achieved without residual chordee, urethral fistula or stricture. CONCLUSIONS: A watch shaped buccal mucosa graft for simultaneous curvature correction and urethroplasty could be a good choice for single stage repair of scrotal hypospadias with severe chordee. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e836-e836 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Miroslav Djordjevic* More articles by this author Abdulmuttalip Simsek More articles by this author Marta Bizic More articles by this author Borko Stojanovic More articles by this author Joshua Roth More articles by this author Rajveer Purohit More articles by this author Expand All Advertisement PDF downloadLoading ...

PROTECTIVE EFFECT OF LOW LEVEL LASER THERAPY ON DORSAL SKIN FLAPS SURVIVAL: RELEVANCE TO CYTOKINES SECRETION.

The loss of skin flaps (SF) due to tissue necrosis can be catastrophic, even with mortality, especially when there is exposure of large vessels or noble structures. This outcome occurs between 2 to 20% of the procedures performed. There is no currently adjuvant treatment that improves the survival of cutaneous flaps, without side effects or significant risks. Recent studies have sought to prove the efficiency of photobiomodulation (PBM) by means of Low Level Laser Therapy (LLLT) and present promising results for increased SF survival.OBJECTIVETo evaluate the effect of LLLT in dorsal skin flaps of mice in terms of tissue necrosis extent as well as biochemical analysis of pro and anti‐inflammatory cytokines.METHODSForty‐eighth Balb/C (20–25 g) male mice were randomly distributed into two groups with twenty‐four animals each; (1) control group that was not submitted to laser irradiation and (2) experimental group that was submitted to laser irradiation on the flap pedicle with a 660 nm wavelength, exposure radiant of 2.25 J/cm2 for a total time of 20 s/point. The treatment started immediately after performing the cranial base random skin flap (3× 1 cm dimension). The animals were euthanized after the evaluation of the percentage of necrosis area, blood and skin tissue was collected for analysis of cytokines and histology on 4th, 7th and 10th postoperative days. Results demonstrated that LLLT irradiation reduced the area of necrosis, significantly decreased IL‐1, IL‐6 and TNF‐α and increased IL‐10 cytokines compared to the non‐irradiated control group. In conclusion, LLLT may improve the healing of skin flaps by decreasing pro‐inflammatory cytokines and increasing the anti‐inflammatory IL‐10.Serum Interleukines after low level laser therapy (gray) versus control group (black). Significant decrease in pro‐inflamatories interleukines 1, 6 and tumor necrosis factor alfa and significant increase in anti‐inflamatory interleukin 10 after 4, 7 and 10 days post‐op.Figure 1

The Effect of Topical Tacrolimus on Pedicled Flap Survival.

Skin necrosis is a known postoperative complication of mastectomies. The pathophysiology of tissue necrosis involves lymphatic congestion, followed by venous congestion and ultimately arterial insufficiency. Recent mouse model studies have shown topical tacrolimus to increase growth of lymphatic collateral vessels and decrease lymphedema, potentially obviating the cycle of necrosis and increasing skin survival. The purpose of this study was to investigate the effect of topical tacrolimus on skin flap necrosis in a rat model. A cranially based dorsal skin flap measuring 3 × 10 cm was raised and reinset on 22 Sprague-Dawley rats. They were then randomized to either the control (topical petroleum jelly) or the treatment (topical 0.1% tacrolimus) arm. In addition, 0.2 g of either ointment was spread over the flap and then covered with an occlusive dressing. Dressings were changed daily with reapplication of both the topical ointment and occlusive dressing. The rats were sacrificed 7 days postoperatively; areas of viable tissue, reversible ischemia, and full thickness necrosis were measured with Fiji software, and comparative analysis was performed with GraphPad statistical software. The average area of the dorsal flaps in the control and tacrolimus groups was 22.5 and 23.9 cm, respectively. In the control cohort, the average viable area was 42.4%, the average reversible ischemia area was 43.6%, and the average necrotic area was 13.9%. In the tacrolimus cohort, the average viable area was 31.5%, the average reversible ischemia area was 59.3%, and the average necrotic area was 9.2%. Total necrotic area was significantly lower in rats receiving topical tacrolimus as compared with controls (P = 0.015). Furthermore, the ratios of necrotic to reversible ischemia and necrotic to viable tissue were significantly lower in the tacrolimus group as compared with controls (P = 0.003, P = 0.015). There was one incidence of wound dehiscence secondary to rodent self-removal of dressings and suture that required reoperation and reinset. Topical tacrolimus was associated with significantly less full thickness necrosis as compared with topical.

Total Nasal Tip Defect: Bilateral Lateral Nasal Artery Flaps for Lining Reconstruction

ABSTRACT Background In full-thickness nasal defects, the internal lining is perhaps the most challenging aspect of the three layers to rebuild. Nasal damage is usually more concentrated on the tip, soft triangles, alar wings, and columella, but the lateral nasal arteries are often left intact and the damage to the dorsal sidewalls are normally superficial. Methods Twelve patients who required total nasal reconstruction received a forehead flap placement as external coverage and autologous rib cartilage as structural support. Residual normal/superficial scar tissue flaps on the dorsal sidewalls with lateral nasal artery pedicles were mobilized and designed for internal lining repair without creating secondary donor site damage. The flaps were then turned 180° downward and placed between the alar medial angles and the fornix. Results No total lining flap necrosis occurred in all the patients. Partial necrosis occurred on the distal edge owing to overpressure of the nostril splint to the flaps; however, the wounds eventually healed, and the nasal structural integrity was preserved. The patients were satisfied with the aesthetic results and had no complaints of airway stenosis. Conclusions Lateral nasal artery pedicle dorsal sidewall skin flaps are appropriately thick, providing enough nostril circumferential support to improve airway stenosis. It allows sufficient blood supply and creates no extra donor site damage. Blood vessels and skin flaps are often undamaged, thereby allowing maximum application in total nasal reconstruction.

PROKSİMAL HİPOSPADİASLI VE CİDDİ KORDİLİ ÇOCUKLARIN İKİ AŞAMALI AMELİYAT SONUÇLARININ HİPOSPADİAS OBJEKTİVE PENİL SKORLAMA (HOPS) İLE DEĞERLENDİRİLMESİ

AbstractPurposeSurgical management for the severe proximal hypospadias remains controversial and it might be challenging. In this study,we evaluated the surgical outcome of patients with proximal hypospadias managed by two staged repair with dorsal prepucial flaps.Patients and MethodsForty one boys with proximal hypospadias are enrolled between January 2006 and September 2016. The location of the urethral meatus was at the penoscrotal junction (PSH), at the scrotum (SH) or at the perineum (PRH). First stage; chordee was released and the prepucial flaps were constructed. Second stage; urethroplasty was performed according to Thiersch-Duplay principle. We assessed postoperative complication rates and utilized Hypospadias Objective Penile Evaluation (HOPE) scoring to evaluate the cosmetic outcome.ResultsThere are a total of 41 boys (31 PSH(%76), 3 SH(%7) and 7 PRH(%17). The mean age at first operation was 15±5,3 months. The mean interval between the stages of the surgical procedures was 10.1±4.,9months.Sixteen patients had various enzyme deficiency or dysgenesis. In two patients, diverticulum is developed after the repair. stenosis has encountered in 10 patients and fistula in 5. Two patients had dehiscence at glanular level. Relation did not demonstrated between the severity of hypospadias and development of fistula, stricture and diverticulum (p&amp;gt;0,05). HOPE scores; 9,4 for the position of the meatus, 5,8 for shape of the meatus, 7,2 for shape of the glans penis, 9,3 for penile torsion and 9,8 penile curvature. Conclusion Incorporating the dorsal prepucial skin flaps in staged procedures has both satisfactory cosmetic and functional success rates.

The Effects of TGF-β Signaling on Cancer Cells and Cancer Stem Cells in the Bone Microenvironment.

Background: Transforming growth factor-β (TGF-β) plays a key role in bone metastasis formation; we hypothesized the possible involvement of TGF-β in the induction of cancer stem cells (CSCs) in the bone microenvironment (micro-E), which may be responsible for chemo-resistance. Methods: Mouse mammary tumor cells were implanted under the dorsal skin flap over the calvaria and into a subcutaneous (subQ) lesions in female mice, generating tumors in the bone and subQ micro-Es. After implantation of the tumor cells, mice were treated with a TGF-β R1 kinase inhibitor (R1-Ki). Results: Treatment with R1-Ki decreased tumor volume and cell proliferation in the bone micro-E, but not in the subQ micro-E. R1-Ki treatment did not affect the induction of necrosis or apoptosis in either bone or subQ micro-E. The number of cells positive for the CSC markers, SOX2, and CD166 in the bone micro-E, were significantly higher than those in the subQ micro-E. R1-Ki treatment significantly decreased the number of CSC marker positive cells in the bone micro-E but not in the subQ micro-E. TGF-β activation of the MAPK/ERK and AKT pathways was the underlying mechanism of cell proliferation in the bone micro-E. BMP signaling did not play a role in cell proliferation in either micro-E. Conclusion: Our results indicated that the bone micro-E is a key niche for CSC generation, and TGF-β signaling has important roles in generating CSCs and tumor cell proliferation in the bone micro-E. Therefore, it is critically important to evaluate responses to chemotherapeutic agents on both cancer stem cells and proliferating tumor cells in different tumor microenvironments in vivo.

Penile skin flap: a versatile substitute for anterior urethral stricture.

ABSTRACTPurpose Penile skin flap uretroplasty is a useful technique for a long urethral stricture due to the ample length and surgical handling characteristics. We investigated the surgical technique and initial results of uretroplasty for anterior urethral strictures using a dorsal penile skin flap.Patients and methods From January 2003 to January 2018, a total of 77 patients underwent substitution urethroplasty using dorsal penile skin flap for bulbar urethral strictures in our institution. All patients were assessed preoperatively, and followed postoperatively by physical examination, urinalysis, retrograde and voiding urethrography, uroflowmetry and post-void residual urine measurement. Success was defined as no requirement of additional urethral instrumentation.Results The mean age was 45 years (10-87). The mean stricture length was 5cm (3-10cm). The mean flap length was 6cm. Urinary fistula was the most common postoperative complication. The mean follow-up was 60 months (6-120). The overall success rate was 88%. Recurrent strictures were found in 4 patients (5%) at 1 year. At 3 year follow-up, 5 (7%) more patients had recurrences. All recurrences were managed by internal urethrotomy.Conclusions Substitution urethroplasty using penile skin flap appear to be a safe and efficient technique for the treatment of a long and complex anterior urethral stricture. It provides encouraging cosmetic and functional results.

Penile urethroplasty using Orandi's dorsal skin flap: a new technique.

To describe, step by step, a new one-stage dorsal skin flap urethroplasty for penile stricture repair. The surgery was accomplished through a midline incision on the ventral penile surface, the urethra was fully dissected from the corpora cavernosa and longitudinally opened along its dorsal surface. A penile skin island, based on the dartos fascia flap, was dissected and moved over the corpora cavernosa, and the urethra was moved and sutured over the penile skin flap. Out of the 12 cases, 10 were classified successful and there were two failures. The operating time was 60min. There was no postoperative fistula or urethral diverticulum. Our modified Orandi's technique was easy and feasible, and avoided fistula and diverticulum formation after repair.

Sumatriptan Increases Skin Flap Survival through Activation of 5-Hydroxytryptamine 1b/1d Receptors in Rats: The Mediating Role of the Nitric Oxide Pathway.

Random pattern skin flaps are applicable for reconstructing any defect in plastic surgery. However, they are difficult to apply because of necrosis. Sumatriptan, a selective 5-hydroxytryptamine 1b/1d agonist, is routinely used to offset acute migraine attacks. Recent studies have suggested that sumatriptan may induce vasodilation at lower concentrations. The authors' aim is to investigate the effect of sumatriptan on skin flap survival and the role of nitric oxide in this phenomenon. Seventy-two male Sprague-Dawley rats were divided into eight groups. Increasing doses of sumatriptan (0.1, 0.3, and 1 mg/kg) were given intraperitoneally to three different groups after dorsal random pattern skin flaps were performed. To assess the exact role of 5-hydroxytryptamine 1b/1d receptors, GR-127935 was administered solely and with sumatriptan. N-ω-nitro-L-arginine methyl ester (L-NAME, a nonselective nitric oxide synthase inhibitor) was used to evaluate any possible involvement of nitric oxide in this study. All rats were examined 7 days later. The authors' results demonstrated that flap survival was increased by lower doses of sumatriptan compared to a control group for both 0.3 mg/kg (p = 0.03, mean difference = 32, SE = 8) and 0.1 mg/kg (p = 0.02, mean difference = 26, SE = 8). This protective effect was eliminated by coadministration of GR-127935 or N-ω-nitro-L-arginine methyl ester with sumatriptan. Histopathologic studies revealed a significant increase in capillary count and collagen deposition and a decreased amount of edema, inflammation, and degeneration. Sumatriptan in lower concentration increases skin flap survival by means of activation of 5-hydroxytryptamine 1b/1d receptors. This effect is mediated through the nitric oxide synthase pathway.

Objective Scoring Outcome Analysis of Redo Urethroplasty for Failed Hypospadias

Background: Failed hypospadias refers to any hypospadias repair that leads to complicationsor causes patient dissatisfaction. One of the commonest major complications of hypospadias surgery is urethrocutaneous fistula.&#x0D; Objectives: Present study aimed to determine a better procedure of salvage urethroplasty for failed hypospadias, caused by persistentlarge (&gt;4mm) or multiple -small (&lt;4mm) fistulae, by a randomized comparison.&#x0D; Patients and Methods. This interventional study was performed in the department of Paediatric Surgery, Rajshahi Medical College Hospital, Rajshahi, Bangladesh, over a period of five years (from July 2011 to June, 2016). A total of 189 patients were included in present study and randomized in the three groups under study. Comparisons were made among three procedures of salvage urethroplasty of failed hypospadias caused by urethrocutaneous fistula using substitution of dorsal skin flap, Flip flap, or buccal mucosal graft in a controlled situation. Outcomes were assessed by means of objective scoring system.&#x0D; Results: Refistula rate, devascularization of flap and grafts and wound dehiscence rate were significantly less in Buccal mucosal graft (group A) than flip flap(group C) and dorsal transposition flap (group B ). This led to a higher success rate and better patient compliance in buccal mucosal graft. The objective scoring evaluation revealed that score gain of BM group (182) was significantly higher than that of dorsal transposition flap (112) and flip flap (89) at P value &lt;0.05 .&#x0D; Conclusion: Staged redo urethroplasty for large or multiple-small fistulae using substitution of buccal mucosal graft revealed as an better option for urethral reconstruction than dorsal transposition flap and flip flap procedures (group A˃ group B ˃group C).&#x0D; TAJ 2018; 31(1): 38-45

Preventing nasal airway collapse with irradiated homologous costal cartilage versus expanded\xa0polytetrafluoroethylene: a novel animal model for nasal airway reconstruction

Airway collapse can occur when the forces of inhalation overpower the strength of the nasal lining flap. The authors established an animal model of the reconstructed nasal airway, and examined mechanical properties of tissue composites based on various materials. Twenty-three Sprague-Dawley rats were divided into three experimental groups: control (n = 5), irradiated homologous costal cartilage (IHCC, n = 10), and expanded polytetrafluoroethylene (ePTFE, n = 8). Two dorsal skin flaps represented nasal lining and skin envelope. No framework, an IHCC or ePTFE rim graft was used as framework. At three weeks, changes in the cross-sectional area of the lining flap were measured when negative pressure was applied. En-bloc specimens containing the graft and soft tissue were examined for histological change and tissue ingrowth. Reduction of cross-sectional area with simulated inhalation was 87.74% in the control group, 82.76% (IHCC), and 67.29% (ePTFE). Cross-sectional reduction was significantly less in ePTFE group than control group (p = 0.004) and IHCC group (p = 0.001). The difference was not significant in the control and IHCC groups. There was histologic evidence of tissue ingrowth in the ePTFE group. This novel animal model of nasal airway reconstruction supports the use and potential benefit of using ePTFE for prevention of airway collapse.

Perioperative Treatment with a Prolyl Hydroxylase Inhibitor Reduces Necrosis in a Rat Ischemic Skin Flap Model.

The hypoxia-inducible factor (HIF) pathway, regulated by prolyl hydroxylase, is central to tissue adaptation to ischemia. The authors tested whether the prolyl hydroxylase inhibitor dimethyloxalylglycine reduces skin flap necrosis. Dorsal skin flaps were raised on hairless rats, with dimethyloxalylglycine delivered intraperitoneally and/or topically for 7 days before and after surgery. After 14 treatment days, percentage of flap necrosis was compared grossly and tissue perfusion compared with an in vivo imaging system. Angiogenesis was compared using immunohistochemical CD31 staining and enzyme-linked immunosorbent assay for tissue vascular endothelial growth factor. Expression levels of HIF-1α and terminal deoxynucleotidyl transferase-mediated dUDP end-labeling were compared using immunohistochemical staining. Complete blood counts and gross necropsy specimens were obtained to assess systemic toxicity. Dimethyloxalylglycine administration significantly improved postoperative flap viability, with combined topical and intraperitoneal dimethyloxalylglycine administration leading to reduced necrosis on postsurgical day 7 at 6 mg/kg/day, 12 mg/kg/day, 24 mg/kg/day, and 48 mg/kg/day versus controls (all p < 0.05). Compared with controls (unperfused, 39.9 ± 3.8 percent), dimethyloxalylglycine treatment led to a dose-dependent decrease in unperfused tissue at 6 mg/kg/day (11.4 ± 1.7 percent), 12 mg/kg/day (9.4 ± 4.2 percent), 24 mg/kg/day (4.7 ± 2.6 percent), and 48 mg/kg/day (1.4 ± 0.9 percent) (all p < 0.001). Topical dimethyloxalylglycine application alone administered at 48 mg/kg/day was sufficient to improve flap viability (p = 0.005). Dimethyloxalylglycine-treated flaps exhibited higher CD31 staining (p = 0.004), tissue vascular endothelial growth factor (p = 0.007), HIF-1α staining (p < 0.001), and reduced terminal deoxynucleotidyl transferase-mediated dUDP end-labeling staining (p = 0.045). There were no differences in hematocrit or macroscopic organ changes on gross necropsy. Topical and systemic targeting of the HIF-1 pathway may be a promising therapeutic approach to improve flap resistance to ischemia.