Conjugated Bile Acids Accelerate Progression of Pancreatic Cancer Metastasis via S1PR2 Signaling in Cholestasis.

BACKGROUND: Pancreatic cancer (PC) has an extremely high mortality rate, where obstructive jaundice due to cholestasis is a classic symptom. Conjugated bile acids (CBAs) such as taurocholic acid (TCA) have been reported to activate both the ERK1/2 and AKT signaling pathways via S1P receptor 2 (S1PR2) and promote growth of cholangiocarcinoma. Thus, we hypothesize that CBAs, which accumulate in cholestasis, accelerate PC progression via S1PR2. METHODS: Murine Panc02-luc and human AsPC-1, MIA PaCa2, and BxPC-3 cells were treated with TCA, S1PR2 agonist CYM5520, S1PR2 antagonist JTE-013, sphingosine-1-phosphate (S1P), and functional S1P receptor antagonist (except S1PR2) FTY720. Bile duct ligation (BDL) was performed on liver implantation or intraperitoneal injection of Panc02-luc cells. RESULTS: Panc02-luc and AsPC-1 cells predominantly expressed S1PR2, and their growth and migration were stimulated by TCA or CYM5520 in dose-dependent manner, which was blocked by JTE-013. This finding was not seen in PC cell lines expressing other S1P receptors than S1PR2. Panc02-luc growth stimulation by S1P was not blocked by FTY720. BDL significantly increased PC liver metastasis compared with sham. PC peritoneal carcinomatosis was significantly worsened by BDL, confirmed by number of nodules, tumor weight, bioluminescence, Ki-67 stain, ascites, and worse survival compared with sham. CYM5520 significantly worsened PC carcinomatosis, whereas treatment with anti-S1P antibody or FTY720 also worsened progression. CONCLUSIONS: CBAs accelerated growth of S1PR2 predominant PC both in vitro and in vivo. This finding implicates S1PR2 as a potential therapeutic target in metastatic S1PR2 predominant pancreatic cancer.

Vascular endothelium as a target tissue for short-term exposure to low-frequency noise that increases cutaneous blood flow.

Harmful health effects of exposure to low-frequency noise (LFN) defined as noise with frequencies at ≤100 Hz on the circulatory system have been a concern. However, there has been no study on the effects of exposure to LFN on the circulatory system with consideration of its frequencies and decibels. In this study, the effects of short-term exposure to broad-band LFNs and their pure-tone components (pure-tone LFNs) on cutaneous blood flow in the extremities including the hands were investigated. In our fieldwork study, we first sampled some kinds of common broad-band LFNs. Our human study then showed that broad-band LFN with a narrower frequency range more strongly increased cutaneous blood flow than did broad-band LFN with a wider frequency range. Pure-tone LFNs of 70-100 Hz at ≤85 dB(Z), but not pure-tone LFNs exceeding 100 Hz, further increased levels of cutaneous blood flow. Our wavelet-transform spectrum analysis of cutaneous blood flow next revealed that the nitric oxide (NO)-dependent and -independent vascular activities of the vascular endothelium were specifically increased by exposure to pure-tone LFN. Our animal study again indicated that exposure to pure-tone LFN increased cutaneous blood flow in mice with impairments of bilateral inner ears as well as cutaneous blood flow in control mice, suggesting a limited effect of inner ear function on the LFN-mediated increase in cutaneous blood flow. The NO-dependent suppressive effect of pure-tone LFN on cutaneous blood flow was confirmed by inhibition of vascular endothelial activity through intravenous injection of an NO inhibitor in wild-type mice. Taken together, the results of this study demonstrated that the vascular endothelium is a target tissue of LFN and that NO is an effector of the LFN-mediated increase in cutaneous blood flow. Since improvement of peripheral circulation could generally promote human health, short-term exposure to LFN may be beneficial for health.

Potential application of a hydrotalcite-like compound for reduction of toxicity to aquatic organisms via rapid and efficient removal of hydrogen sulfide.

Hydrogen sulfide (H2S) is known to have wide ranging toxicities not only as a gas but also as dissolved forms in aquatic environments. The diversity of aquatic organisms can be severely affected by hydrogen sulfide at very low concentrations, indicating the urgent necessity to develop an efficient method for removal of hydrogen sulfide in water. In this study, the removal capacity for hydrogen sulfide of our originally developed hydrotalcite-like compound composed of magnesium and iron (MF-HT) was investigated and its potential application for reduction of toxicity to aquatic organisms was evaluated. The MF-HT experimentally showed a high adsorption capacity of 146.5 mg/g with a fast adsorption equilibrium time of 45 min, both of which are top-class compared with those of other adsorbents previously reported. In fact, removal of hydrogen sulfide (1.2-152.5 mg/L) at an average rate of >97.6% was achieved in groundwater samples (n = 16) by the MF-HT within 60 min. The toxicities of groundwater, indicated by inhibition rate for microalgae (primary producers) and immobilization rate for crustaceans (secondary consumers), were reduced by 96.1% and 82.5% in 2-fold and 4-fold diluted groundwater, respectively, after treatment with the MF-HT for 60 min. These results indicate that MF-HT has an excellent safety record for aquatic organisms. After clarifying the adsorption mechanism, excellent reusability of MF-HT was also confirmed after regeneration using 1 M Na2CO3 solution. Considering the efficacy, speed, safety and cost of MF-HT, it could be a novel promising material for solving the problem of hydrogen sulfide pollution in the hydrosphere.

Decreased hearing levels at frequencies for understanding speech in tannery workers exposed to a high level of trivalent chromium in Bangladesh.

Hexavalent chromium [Cr(VI)], which has a strong corrosive effect, has been reported to cause perforation of the eardrum. Trivalent chromium [Cr(III)] also has a weak corrosive effect. However, there has been no study on the effects of exposure to Cr, either Cr(VI) or Cr(III), on hearing levels in animals or humans. In this study, the effect of Cr(III) exposure on hearing levels was determined in a human study. Then the reproducibility of the results obtained in the human study and the etiology were investigated in an animal study. The mean levels of total chromium (t-Cr) in hair and toenails from 100 Bangladeshi tannery workers were >20-fold and >360-fold higher, respectively, than those in hair and toenails from 49 Bangladeshi non-tannery workers (office workers). Multivariate analysis revealed decreases of hearing levels (DHLs) at 1 k and 4 k Hz, frequencies that are crucial for understanding language, but not at 8 k and 12 k Hz, in the tannery workers. Since >99.99% of t-Cr in the wastewater that the workers were in direct contact with in the tanneries was Cr(III), the epidemiological results suggest Cr(III)-mediated DHLs in the tannery workers. The results of animal experiments in this study further showed that treatment with eardrops but not intraperitoneal injection with the same amount of Cr(III) that tannery workers might be exposed to resulted in DHL with a damaged eardrum in mice. Previous studies suggested that Cr(III) can directly reach the eardrums of tannery workers via droplets in the air. Cr(III) could also reach the eardrum via picking an ear canal with a finger contaminated with tannery wastewater including Cr(III). Taken together, the results of both human and animal studies suggest the risk of DHLs caused by damage of the eardrum through external exposure to Cr(III) via the ear canal.

Development of an efficient remediation system with a low cost after identification of water pollutants including phenolic compounds in a tannery built-up area in Bangladesh.

Water pollution caused by tannery wastewater is an important issue in developing countries. Most studies have focused on inorganic chemicals represented by chromium as a tannery-related main pollutant. This is the first study in which pollution of water by tannery-related organic chemicals was assessed by a combination of qualitative and quantitative analyses. Our quantitative analysis showed that the maximum concentration of total phenolic compounds (phenols), consisting of phenol, bisphenol F, p-cresol and chlorocresol, in canal water in a tannery built-up area in Bangladesh was >67-fold higher than the Environmental, Health and Safety (EHS) guideline value. Mapping of our results indicated tanneries as the sources of phenols pollution. Our original depurative, a hydrotalcite-like compound consisting of magnesium and iron (MF-HT), could adsorb all kinds of phenols and exhibited the highest phenol adsorption ability (115.8 mg/g) among reported hydrotalcite-like compounds. The levels of phenols in canal water samples were reduced to levels below the guideline value by using MF-HT with assistance of a photocatalytic reaction. Moreover, the mean level of chromium (112.2 mg/L) in canal water samples was decreased by 99.7% by using the depurative. Thus, the depurative has the potential for solving the problem of tannery-related water pollution by phenols and chromium.

Intranasal levels of lead as an exacerbation factor for allergic rhinitis in humans and mice.

BACKGROUND: Air pollutants are suspected to affect pathological conditions of allergic rhinitis (AR). OBJECTIVES: After detecting Pb (375 µg/kg) in Japanese cedar pollen, the effects of intranasal exposure to Pb on symptoms of AR were investigated. METHODS: Pollen counts, subjective symptoms, and Pb levels in nasal epithelial lining fluid (ELF) were investigated in 44 patients with Japanese cedar pollinosis and 57 controls from preseason to season. Effects of intranasal exposure to Pb on symptoms were confirmed by using a mouse model of AR. RESULTS: Pb levels in ELF from patients were >40% higher than those in ELF from control subjects during the pollen season but not before the pollen season. Pb level in ELF was positively associated with pollen counts for the latest 4 days before visiting a hospital as well as scores of subjective symptoms. Intranasal exposure to Pb exacerbated symptoms in allergic mice, suggesting Pb as an exacerbation factor. Pb levels in ELF and nasal mucosa in Pb-exposed allergic mice were higher than those in Pb-exposed nonallergic mice, despite intranasally challenging the same amount of Pb. Because the increased Pb level in the nasal mucosa of Pb-exposed allergic mice was decreased after washing the nasal cavity, Pb on the surface of but not inside the nasal mucosa may have been a source of increased Pb level in ELF of allergic mice. CONCLUSIONS: Increased nasal Pb level partially derived from pollen could exacerbate subjective symptoms of AR, indicating Pb as a novel hazardous air pollutant for AR.

The Latest Strategy for Keloid and Hypertrophic Scar Prevention and Treatment: The Nippon Medical School (NMS) Protocol.

In 2006, we established a scar/keloid-specialized unit in the Department of Plastic, Reconstructive, and Aesthetic Surgery at Nippon Medical School (NMS) in Tokyo, Japan. In the ensuing 15 years, we treated approximately 2,000 new scar/keloid patients annually. This extensive experience has greatly improved the efficacy of the treatments we offer. Therefore, we discuss here the latest NMS protocol for preventing and treating keloids and hypertrophic scars. While this protocol was optimized for Japanese patients, our experience with a growing body of non-Japanese patients suggests that it is also effective in other ethnicities. The extensive evidence-based experience underlying the NMS protocol suggests that it may be suitable as the foundation of a standard international prevention/treatment algorithm for pathological scars.

Combination Therapy Composed of Surgery, Postoperative Radiotherapy, and Wound Self-management for Umbilical Keloids.

BACKGROUND: A universally accepted therapeutic strategy for umbilical keloids has not been determined. Our team has had considerable success with combination therapy composed of surgical excision followed by postoperative radiotherapy and steroid plaster/injection. METHODS: All consecutive patients with umbilical keloids that developed from endoscopic surgical scars and underwent minimal-margin keloid excision followed by umbilicoplasty with a flap if needed, tension-reduction suturing, and postoperative radiotherapy in 2013-2017 in the keloid/scar-specialized clinic at the Department of Plastic, Reconstructive and Aesthetic Surgery of Nippon Medical School. The postsurgical radiotherapy regimen was 15 Gy administered in 2 fractions over 2 consecutive days. Radiotherapy was followed by tension-reducing wound self-management with silicone tape or, if needed, steroid plaster. The primary study focus was keloid recurrence during the 24-month follow-up period. Recurrence was defined as the growth of stiff red lesions in even small areas of the scar that was refractory to 2-6 months of steroid-plaster therapy. RESULTS: The case series consisted of 34 patients with 34 lesions. Three lesions (8.8%) recurred. One recurrence was successfully treated by concomitant steroid plaster/injection. The other 2 cases were resistant to steroid injection and underwent reoperation without radiotherapy followed by 6 months of steroid-plaster therapy. None of the 3 cases recurred within 2 years of steroid plaster/injection completion or reoperation. CONCLUSION: Umbilical keloids can be successfully treated by customized treatment plans that involve appropriate surgical modalities (including umbilicoplasty, if required), postoperative radiotherapy (15 Gy/2 fractions/2 days), and wound/scar self-management with silicone tape and steroid plaster.

Direct Delivery of Apatite Nanoparticle-Encapsulated siRNA Targeting TIMP-1 for Intractable Abnormal Scars.

Hypertrophic scars (HSs) and keloids are histologically characterized by excessive extracellular matrix (ECM) deposition. ECM deposition depends on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteases (TIMPs). TIMP-1 has been linked to ECM degradation and is therefore a promising therapeutic strategy. In this study, we generated super carbonate apatite (sCA) nanoparticle-encapsulated TIMP-1 small interfering RNA (siRNA) (siTIMP1) preparations and examined the effect of local injections on mouse HSs and on ex vivo-cultured keloids. The sCA-siTIMP1 injections significantly reduced scar formation, scar cross-sectional areas, collagen densities, and collagen types I and III levels in the lesions. None of the mice died or exhibited abnormal endpoints. Apatite accumulation was not detected in the other organs. In an ex vivo keloid tissue culture system, sCA-siTIMP1 injections reduced the thickness and complexity of collagen bundles. Our results showed that topical sCA-siTIMP1 injections during mechanical stress-induced HS development reduced scar size. When keloids were injected three times with sCA-siTIMP1 during 6 days, keloidal collagen levels decreased substantially. Accordingly, sCA-siRNA delivery may be an effective approach for keloid treatment, and further investigations are needed to enable its practical use.

Gene Expression Profile of Isolated Dermal Vascular Endothelial Cells in Keloids.

Wound healing is a complex biological process, and imbalances of various substances in the wound environment may prolong healing and lead to excessive scarring. Keloid is abnormal proliferation of scar tissue beyond the original wound margins with excessive deposition of extracellular matrix (ECM) and chronic inflammation. Despite numerous previous research efforts, the pathogenesis of keloid remains unknown. Vascular endothelial cells (VECs) are a major type of inductive cell in inflammation and fibrosis. Despite several studies on vascular morphology in keloid formation, there has been no functional analysis of the role of VECs. In the present study, we isolated living VECs from keloid tissues and investigated gene expression patterns using microarray analysis. We obtained 5 keloid tissue samples and 6 normal skin samples from patients without keloid. Immediately after excision, tissue samples were gently minced and living cells were isolated. Magnetic-activated cell sorting of VECs was performed by negative selection of fibroblasts and CD45+ cells and by positive selection of CD31+cells. After RNA extraction, gene expression analysis was performed to compare VECs isolated from keloid tissue (KVECs) with VECs from normal skin (NVECs). After cell isolation, the percentage of CD31+ cells as measured by flow cytometry ranged from 81.8%-98.6%. Principal component analysis was used to identify distinct molecular phenotypes in KVECs versus NVECs and these were divided into two subgroups. In total, 15 genes were upregulated, and 3 genes were downregulated in KVECs compared with NVECs using the t-test (< 0.05). Quantitative RT-PCR and immunohistochemistry showed 16-fold and 11-fold overexpression of SERPINA3 and LAMC2, respectively. SERPINA3 encodes the serine protease inhibitor, α1-antichymotripsin. Laminin γ2-Chain (LAMC2) is a subunit of laminin-5 that induces retraction of vascular endothelial cells and enhances vascular permeability. This is the first report of VEC isolation and gene expression analysis in keloid tissue. Our data suggest that SERPINA3 and LAMC2 upregulation in KVECs may contribute to the development of fibrosis and prolonged inflammation in keloid. Further functional investigation of these genes will help clarify the mechanisms of abnormal scar tissue proliferation.

The Immunosuppressant Fingolimod (FTY720) for the Treatment of Mechanical Force-Induced Abnormal Scars.

AIM: Abnormal scars such as hypertrophic scars (HSs) and keloids are excessively growing scars that exhibit chronic inflammation and capillary vasculogenesis. The lipid mediator sphingosine-1-phosphate (S1P) is important in inflammatory cell recruitment and angiogenesis. Fingolimod (FTY720) is an analog of S1P and thus functionally antagonizes S1P receptors and inhibits the enzyme that produces S1P. We examined the effects of topical FTY720 injections on mechanical force-induced HS progression. METHODS: Mechanical force-induced HSs were generated in C57BL6/J mice by suturing a dorsal incision and applying a stretching device on Days 6, 8, 10, and 12. On Days 8, 10, and 12, intracutaneous FTY720 (10 µM) or control vehicle injections were performed. On Day 14, scar tissues and blood were procured and subjected to histology and flow cytometry. RESULTS: Flow cytometry showed that FTY720 decreased the frequencies of macrophages with M2 predominance in the scars but had no effect on total, CD4+, or CD8a+ T cell frequencies. FTY720 also decreased the vascular endothelial cell frequencies in the scar along with the microvessels, as determined by immunohistochemistry. Compared to the vehicles, FTY720 treatment significantly reduced the gross scar area and the cross-sectional scar area on histology. On the other hand, FTY720 tended to reduce white blood cells and significantly reduced the lymphocyte frequencies in the blood. CONCLUSION: Topical FTY720 induces M2 predominance and impairs angiogenesis. Therefore, its local immunosuppressive mechanisms differ from those of conventional immunosuppressive agents. Topical FTY720 can be a novel therapeutic option for abnormal scars that are difficult to control with corticosteroids. Its lymphocytopenic effects may be limited by careful optimization of the treatment regimen.

Geometric modeling and a retrospective cohort study on the usefulness of fascial tensile reductions in severe keloid surgery.

BACKGROUND: Severe keloids are currently treated with surgical resection followed by radiation. Radiotherapy is essential for preventing recurrences. Fascia tensile reduction suturing may also prevent recurrence. We asked whether superficial fascia tensile reduction with or without deep fascia tensile reduction reduced skin mechanical tension and yielded good outcomes. METHODS: Geometric modeling on 3-dimensional anatomic shapes assessed the effect of superficial fascia tensile reduction with or without deep fascia tensile reduction on skin tension. A retrospective cohort study was performed on patients with severe anterior-chest keloids with Japan Scar Workshop-scar scale classification score ≥ 16 who underwent resection plus fascia tensile reduction plus radiotherapy between 2011 and 2016 and were followed for >18 months. Patient characteristics and 18-month postoperative outcomes were examined. Postoperative outcome was defined as rates of keloid disappearance, improvement, and obvious recurrence. RESULTS: Maximal mechanical forces placed on the dermis by dermal sutures, dermal sutures plus superficial fascia tensile reduction, and dermal sutures plus superficial fascia tensile reduction plus deep fascia tensile reduction were 4,700, 573, and 697 Pa, respectively. Adding deep fascia tensile reduction to superficial fascia tensile reduction decreased the force on the superficial fascia. Of 77 cohort patients, 27 and 50 underwent superficial fascia tensile reduction and superficial fascia tensile reduction plus deep fascia tensile reduction, respectively. Superficial fascia tensile reduction plus deep fascia tensile reduction patients underwent complete excision more often (60.0% vs 37.0%, P = .046). The groups did not differ in 18-month surgical outcome, including recurrence rate (P = .670). CONCLUSION: Our 2003 study showed that in anterior-chest keloids, resection plus non-fascial suturing plus radiotherapy led to a 43.1% recurrence. Thus, fascia tensile reduction suturing helps reduce anterior-chest keloid recurrence to ∼5.2%. Superficial fascia tensile reduction plus deep fascia tensile reduction is suitable for relatively large keloids that require total resection. Deep fascia tensile reduction may facilitate superficial fascia tensile reduction but may only be useful when it is technically difficult to achieve reduction with superficial fascia tensile reduction alone.

Sphingosine-1-Phosphate Facilitates Skin Wound Healing by Increasing Angiogenesis and Inflammatory Cell Recruitment with Less Scar Formation.

Wound healing starts with the recruitment of inflammatory cells that secrete wound-related factors. This step is followed by fibroblast activation and tissue construction. Sphingosine-1-phosphate (S1P) is a lipid mediator that promotes angiogenesis, cell proliferation, and attracts immune cells. We investigated the roles of S1P in skin wound healing by altering the expression of its biogenic enzyme, sphingosine kinase-1 (SphK1). The murine excisional wound splinting model was used. Sphingosine kinase-1 (SphK1) was highly expressed in murine wounds and that SphK1-/- mice exhibit delayed wound closure along with less angiogenesis and inflammatory cell recruitment. Nanoparticle-mediated topical SphK1 overexpression accelerated wound closure, which associated with increased angiogenesis, inflammatory cell recruitment, and various wound-related factors. The SphK1 overexpression also led to less scarring, and the interaction between transforming growth factor (TGF)-ß1 and S1P receptor-2 (S1PR2) signaling is likely to play a key role. In summary, SphK1 play important roles to strengthen immunity, and contributes early wound healing with suppressed scarring. S1P can be a novel therapeutic molecule with anti-scarring effect in surgical, trauma, and chronic wound management.

Z-plasty and Postoperative Radiotherapy for Upper-arm Keloids: An Analysis of 38 Patients.

Therapies for upper arm keloids include surgical excision followed by postoperative radiotherapy, silicone tape stabilization, and steroid plaster. However, a universally accepted therapeutic strategy for upper-arm keloids is lacking. METHODS: All consecutive patients with single upper-arm keloids who underwent keloid excision followed by tension-reducing suturing, multiple z-plasties, and postoperative radiotherapy in 2013-2016 in the keloid/scar specialist clinic at the Department of Plastic, Reconstructive and Aesthetic Surgery of Nippon Medical School, were included in this case series study. Only keloids that arose from the small injury produced during Bacillus Calmette-Guérin vaccination were selected. The postsurgical radiotherapy regimen was 18 Gy administered in 3 fractions over 3 days. Radiotherapy was followed by tension-reducing wound self-management with silicone tape and, if needed, steroid plaster. The primary study objective was keloid recurrence during the 24-month follow-up period. Recurrence was defined as the growth of stiff red lesions in even small areas of the scar that was refractory to at least 2 months of steroid plaster therapy. RESULTS: In total, 38 patients with 38 lesions were enrolled. Two lesions (5.3%) recurred. Both recurrences were successfully treated by concomitant steroid plaster and steroid injection. The recurrence patients were significantly more likely than the nonrecurrence patients to have multiple keloids. The 2 groups did not differ in terms of original keloid size. CONCLUSIONS: Upper-arm keloids can be successfully treated by customized plans that involve appropriate surgical modalities (including multiple z-plasties), postoperative radiotherapy (18 Gy/3 fractions/3 d), and postoperative wound/scar self-management with silicone tape and steroid plaster.

Cytochrome P450 genes play central roles in transcriptional response by keratinocytes to a high-voltage alternating current electric field.

The endogenous electric field (EF) of skin wounds plays an important role in the biological processes that underlie wound healing. Treatments that modulate wound-EFs promote healing. However, the mechanism(s) that underlie this effect remain unclear. Agilent-based microarrays were used to determine the transcriptomes of the keratinocyte line HaCaT, normal human dermal fibroblasts, and the human dermal endothelial cell line HMEC-1 before and after high-voltage alternating current (AC)-EF (14,000 V, 90 Hz) treatment. The keratinocytes had the most genes whose transcription was altered by EF. They included the cytochrome P450 (CYP) genes CYP1A1 and CYP1B1, HMOX1, EREG, DUSP5, and SLC7A11 (all upregulated), and DOCK8, ABCC6, and CYP26A1 (all downregulated). As shown by transcriptional-network analysis, all three CYP genes played central roles in the EF-induced changes in keratinocyte transcriptome. To the best of our knowledge, this is the first study that demonstrates that CYP genes play a key role in the transcriptional responses of human keratinocytes to EF treatment. Further investigations into the effects of EF on wound healing, aging, and regenerative medicine are likely to yield promising results.

Periauricular Keloids on Face-Lift Scars in a Patient with Facial Nerve Paralysis.

Keloids are caused by excessive scar formation that leads to scar growth beyond the initial scar boundaries. Keloid formation and progression is promoted by mechanical stress such as skin stretch force. Consequently, keloids rarely occur in paralyzed areas and areas with little skin tension, such as the periauricular region. Therefore, periauricular incision is commonly performed for face lifts. We report a rare case of keloids that arose from face-lift scars in a patient with bilateral facial nerve paralysis. A 51-year-old Japanese man presented with abnormal proliferative skin masses in bilateral periauricular scars. Seventeen years before, he had a cerebral infarction that resulted in permanent bilateral facial nerve paralysis. Three years before presentation, the patient underwent face-lift surgery with periauricular incisions. We diagnosed multiple keloids. We removed the masses surgically, closed the wounds with sutures in the superficial musculoaponeurotic system layer to reduce tension on the wound edges, reconstructed the earlobes with local skin flaps, and provided 2 consecutive days of radiotherapy. The wounds/scars were managed with steroid plasters and injections. Histology confirmed that the lesions were keloids. Ten months after surgery, the lesions did not exhibit marked regrowth. The keloids appeared to be caused by the patient's helmet, worn during his 3-hour daily motorcycle rides, which placed repeated tension on the periauricular area. This rare case illustrates how physical force contributes to auricular and periauricular keloid development and progression. It also shows that when performing surgery with periauricular incisions, care should be taken to eliminate wound/scar stretching.

Histological analysis of hyalinised keloidal collagen formation in earlobe keloids over time: collagen hyalinisation starts in the perivascular area.

Keloids grow and do not regress. They are characterised histologically by hyalinised keloidal collagen (HKC). HKC amounts vary, and the mechanism by which they form is unclear. To clarify how HKCs form and whether their formation associates with specific clinical features, we studied the histological findings of earlobe keloids and compared them with respective clinical features. A total of 50 earlobe keloids from 43 patients were used for histological analysis of keloid size (mm2 ), HKC area (mm2 ) and HKC area ratio (%). As a result, keloid durations ranged from 3 months to >13 years. Early-stage keloids exhibited little HKC and a tendency for the HKCs to locate in perivascular regions. In later-stage keloids, the HKCs were extremely interconnected and formed a thick bitten donut-shaped region. HKC area ratios correlated positively with keloid duration (r2 = 0·58, P<0·05). HKC area ratios and keloid durations did not correlate with keloid sizes. These patterns of HKC formation and growth may explain why local therapies, which effectively remove fibroblasts and accumulated collagen but not HKCs, are ineffective in older keloids. Keloids should be promptly treated after diagnosis, and older keloids with extensive HKCs may require surgical excision followed by radiotherapy.

Experimental Rat Skin Flap Model That Distinguishes between Venous Congestion and Arterial Ischemia: The Reverse U-Shaped Bipedicled Superficial Inferior Epigastric Artery and Venous System Flap.

BACKGROUND: The commonly used flap models have drawbacks that limit their usefulness. In the random skin flap model, flap necrosis is caused by both arterial and venous insufficiency. In the axial skin flap model, flap viability is easily affected by the pedicle blood flow and can result in complete necrosis. This study aimed to establish a new rat skin flap model that has a consistent flap survival rate and in which venous congestion and arterial ischemia can be readily distinguished macroscopically. METHODS: Rats underwent reverse U-shaped bipedicled superficial epigastric artery flap elevation. The right superficial epigastric vessels formed the pedicle. In the control rats (n = 3), the left superficial epigastric vessels were left intact. In the ischemia group (n = 10), the left superficial epigastric artery was ligated. In the congestion group (n = 10), the left superficial epigastric vein was ligated. The flap was returned to the original site and sutured. The surrounding neovascularization was blocked by polyurethane film. Flap survival rates were evaluated on postoperative day 3. RESULTS: The flaps in the ischemia and congestion groups were noticeably pale and violet, respectively. Flap necrosis was noted in the contralateral distal zone only. It started on postoperative day 2 in the ischemia and congestion groups. The mean flap survival rates of the control, ischemia, and congestion groups were 100 percent, 61.8 percent (range, 56.9 to 67.1 percent), and 42.3 percent (35.7 to 48.7 percent), respectively (all p < 0.001). CONCLUSIONS: The flap facilitated discrimination of the effects of ischemia and congestion. This new rat skin flap model is simple and easy to construct, and has a consistent flap survival rate.