Expression of collagen-related piRNA is dysregulated in cultured dermal fibroblasts derived from patients with scleroderma.

PIWI-interacting RNA (piRNA) is a class of recently discovered small non-coding RNAs. piRNAs derive from an initial transcript encompassing a piRNA cluster via a unique biosynthesis process, interact with PIWI proteins, bind to specific targets, and recruit chromatin modifiers to enable transcriptional repression. Abnormal expression of PIWI proteins and piRNAs has been reported in some human cancers, with participation of some PIWI/piRNAs complexes in tumorigenesis and association with cancer prognosis. Their expression in patients with systemic sclerosis (SSc) has not been widely elucidated. PIWI/piRNAs and their role in the pathogenesis of collagen accumulation in SSc was therefore investigated; no difference was found in the PIWIL1-4 levels between normal and cultured SSc dermal fibroblasts. Among piRNAs predicted to target SSc-related molecules, we first found significant piR-32364 up-regulation in SSc dermal fibroblasts, likely due to intrinsic TGF-ß signaling. Forced piR-32364 overexpression in normal fibroblasts significantly reduced COL1A1 expression both at mRNA and protein levels, but not COL1A2. Thus, piR-32364 overexpression in SSc fibroblasts may be the negative feedback against collagen up-regulation, which could suggest the potential of piRNAs as a therapeutic target.

Analysis of cytokine profiles in sera of single and multiple infantile hemangioma.

Infantile hemangiomas (IH) are benign vascular tumors that are common in infancy. They vary in growth, size, location, and depth, and although most lesions are relatively small, approximately one fifth of patients have multiple lesions. Risk factors for IH include female sex, low birth weight, multiple gestation, preterm birth, progesterone therapy, and family history, but the mechanism that causes multiple lesions is unclear. We hypothesized that blood cytokines are involved as a cause of multiple IHs, and tried to prove this using sera and membrane arrays from patients with single and multiple IHs. Serum samples were obtained from five patients with multiple lesions and four patients with a single lesion, none of which had received any treatment. Serum levels of 20 cytokines were measured using human angiogenesis antibody membrane array. Four of the 20 cytokines (bFGF, IFN-γ, IGF-I, and TGF-ß1) were higher in the patients with multiple lesions than in those with single lesion, with statistically significant difference (p < 0.05). Notably, signal for IFN-γ was evident in all cases with multiple IHs, but was absent in cases with single IH. Although not significant, there was mild correlation between IFN-γ and IGF-I (r = 0.64, p = 0.065), and between IGF-I and TGF-ß1 (r = 0.63, p = 0.066). bFGF levels were strongly and significantly correlated with the number of lesions (r = 0.88, p = 0.0020). In conclusion, blood cytokines could act as a cause of multiple IHs. This is a pilot study with a small cohort, so further large-scale studies are necessary.

Analysis of onset and clinical characteristics in Japanese patients with infantile hemangioma.

Infantile hemangioma (IH) is a common benign tumor during infancy, although the detailed mechanism behind it has not been fully elucidated. Based on previous studies, we hypothesized that formation of hemangioma might be triggered by secondary physiological events (perinatal hypoxia or mechanical stress during delivery) in patients carrying germline risk mutations. We aimed to clarify the mechanism by evaluating whether head and neck lesions were more frequent in patients in who IH appeared after birth compared with those in who it was present at birth. Clinical data of 62 lesions in 51 patients with IH were collected. All patients were analyzed for correlation of onset with gender, localization, family histories, gestational age, birth weight, and clinical subtypes. Distribution of lesions on the head and neck was slightly more frequent in the after-birth IH group, compared with those with IH present at birth, but without significant difference (47.6% vs. 40.0%, p = 0.32). On the other hand, the ratio of superficial and deep type IH at birth was significantly altered compared with that in IH after birth (19:0 vs. 26:7, p = 0.039). In addition, IHs appearing after birth tended to more commonly have multiple lesions than those with IH present at birth, with statistically significant difference (25.8% vs. 0%, p = 0.0164). There may therefore be different triggers for IHs at birth and IH after birth. Further studies with greater number of patients are necessary to validate these findings.

The clinical significance of cytokeratin 20 staining pattern in Merkel cell carcinoma.

In the present study, to identify the clinical significance of the cytokeratin (CK) 20 staining pattern in Merkel cell carcinoma (MCC), we retrospectively analyzed the major clinicopathological and immunohistochemical characteristics of 12 cases of MCC. Typical dot-like pattern was seen in eight of our patients, while four patients showed peripheral staining pattern. Interestingly, all cases of MCC with dot-like CK20 tumor cells occurred in the head and neck region, while those with peripheral CK20 pattern tended to be located in other lesions (forearm, knee, or buttock): The difference of frequency in the head and neck regions was statistically significant. Dot-like CK20 staining pattern may therefore be resulted from ultraviolet exposure. Additionally, although without significance, metastasis was more frequent in those with dot-like CK20 than in peripheral CK20 staining: All patients with peripheral CK20 pattern had complete remission by surgical excision with or without radiation therapy. CK20 staining pattern may be a novel predictor of prognosis.

Change of serum cytokine profiles by propranolol treatment in patients with infantile hemangioma.

Infantile hemangioma is a benign cutaneous tumor, which sometimes rapidly enlarges, causes cosmetic problem, destroys normal tissue, and possibly threatens life. Dye lasers, steroid administration, and watchful waiting had been the treatment options for infantile hemangioma, but in recent years propranolol therapy has become available. The mechanism underlying the action of propranolol, however, is still unknown. We hypothesized that cytokines whose expressions change before and during the treatment are responsible for the efficacy of the drug. This study aims to prove the hypothesis using patients' sera and membrane array. In this study, the serum cytokine concentrations of five patients with infantile hemangioma were measured using membrane array of 20 angiogenic cytokines. We compared them before and during propranolol treatment to identify the cytokines responsible for the effect of propranolol. Signals for angiogenin, epidermal growth factor (EGF), platelet-derived growth factor-BB (PDGF-BB), regulated on activation, normal T-cell expressed and secreted chemokine (RANTES), tissue inhibitor of metalloproteinases 1 (TIMP-1), and tissue inhibitor of metalloproteinases 2 (TIMP-2) were evident in all five cases before treatment. Furthermore, PDGF-BB was the only cytokine of which concentration was decreased during treatment with statistically significant difference. This report is a pilot study with a small number of samples, and further detailed research with increased number of samples is necessary. Nonetheless, our results suggest that PDGF-BB may be involved in the action of propranolol. In addition, its serum concentration can be utilized as a potential marker of the therapeutic effect.

Difference in distribution of malignant melanoma and melanocytic nevus in the palm and finger.

We conducted a study to try to plot the lesions of melanocytic nevus and malignant melanoma on the palm and fingers, and compared them to identify the different distribution pattern of both lesions. Data on 8 patients with melanomas (4 male and 4 female) and 26 patients with melanocytic nevus (6 male and 20 female) of palm and finger pulp who visited Wakayama Medical University Hospital between 1986 and 2018 was retrospectively collected. We found that all of the 8 lesions of melanoma were located on the finger pulps and distal to the 'distal transverse crease' of the palm, and that melanomas were not present proximal to the transverse crease. On the other hand, melanocytic nevus was present in the proximal area to the distal transverse crease of the palm more frequently than melanomas (50.0% vs. 0%), and there was statistically significant difference (p = 0.011 by Fisher's exact probability test). From these observations, our findings may reveal the contribution of mechanical stress to the cause of palmar melanoma, and may facilitate clinical differentiation between malignant melanoma and melanocytic nevus by the localization. Further studies with increased number of patients are needed to validate the finding.

Distribution analysis of infantile hemangioma or capillary malformation on the head and face in Japanese patients.

Infantile hemangioma is one of the most common tumors in infancy. Delivery may be a clue for the trigger of infantile hemangioma formation in the head and face areas. In this study, we tried to plot localization of infantile hemangioma as well as capillary malformation on the head and face, and compared them to identify their characteristics and risk factors. The distribution of 104 lesions in 100 patients with infantile hemangioma was as follows: 32 lesions on the head, 12 on the forehead, 57 on the cheek and three in the jaw area. We could not find a statistically significant correlation of the distribution with three clinical subtypes (superficial, deep and mixed), sex or size of the lesions. However, the lesions in the jaw or chin areas were significantly less frequent than other areas (P = 0.0008 or 0.03, respectively). This tendency was not found in 40 patients with capillary malformation. Mechanical stress to jaw or chin areas may be less than other areas in normal cephalic delivery. Considering the emergence after birth and age-dependent involution of infantile hemangioma, we speculate that physiological events including perinatal hypoxia or mechanical stress during delivery as the trigger of hemangioma formation. Taken together, our results may reveal the contribution of mechanical stress to the trigger of infantile hemangioma, not capillary malformation, and may facilitate clinical differentiation between the two diseases by their localization. Further studies with an increased number of patients will be necessary to validate the finding.

Clinical and histological evaluation of a single high energy microwave treatment for primary axillary hyperhidrosis in Asians: A prospective, randomized, controlled, split-area comparative trial.

BACKGROUND AND OBJECTIVES: Microwave treatment is an effective non-invasive treatment option for primary axillary hyperhidrosis (PAH), but the treatment parameters vary and no histopathological studies have been performed to validate clinical outcomes. This study investigated its efficacy and safety and histopathological changes after a single microwave treatment at the maximum energy level for PAH in Asians. MATERIALS AND METHODS: A prospective, clinical, and histological split-area randomized controlled trial (RCT) was performed in Japan. Twenty-six subjects underwent a single microwave treatment at the maximum energy level 5 (5.8 GHz/axilla) on the randomized side of axillae. The primary outcome was the mean difference between both sides in the improvement of modified single-underarm Hyperhidrosis Disease Severity Scale (msHDSS) scores over the course of the 12-month study period from baseline. The secondary outcomes were; the percentage of responders with at least a 2-point drop in the msHDSS score of 3 or 4 group or with a 1-point drop in the msHDSS score of 2 group; the percentage of responders with at least a 75% reduction in sweat weight over 12 months; recurrence rate; and adverse effects. We also performed a histological assessment for 13 selected subjects. RESULTS: Twenty-four subjects completed the study. There were statistically significant differences in improvement of msHDSS scores between the microwave-treated and control sides (P < 0.05) from baseline at 0.5, 1, 3, 6, and 12 months. In the msHDSS score of 3 or 4 group, the percentage of responders with at least a 2-point drop on the microwave-treated side versus control side was 72.2 versus 11.1% (P < 0.05) at 1 month, 83.3 versus 5.6% (P < 0.05) at 3 months, 61.1 versus 38.9% (P = 0.317) at 6 months and 38.9 versus 16.7% (P = 0.264) at 12 months. The percentage of responders with at least a 75% reduction in sweat weight on the microwave-treated side versus control side was 75.0 versus 37.5% at 1 month, 75.0 versus 29.2% at 3 months, 83.3 versus 50.0% at 6 months and 70.8 versus 33.3% at 12 months (all P < 0.05). Recurrence on the microwave-treated side was observed in 4.2% and 12.5% of 24 subjects at 3 and 12 months, respectively. No serious side-effects were noted. Histology showed the diameter and density of secretory eccrine glands and nerve fiber lengths around eccrine glands were significantly decreased after treatment compared to baseline (P = 0.002, 0.027, 0.003, respectively). CONCLUSIONS: A single-session microwave treatment at the maximum energy level significantly improved the PAH of Japanese patients and had minimal side effects. This technique demonstrates that diminished size of secretory eccrine glands and nerve fiber degeneration could be useful markers for predicting the efficacy of the treatment. Lasers Surg. Med. 9999:1-8, 2019. © 2019 Wiley Periodicals, Inc.

Prognostic factors of daily blood examination for advanced melanoma patients treated with nivolumab.

Biomarkers to distinguish patients with advanced melanoma responsive to nivolumab are of great interest. Therefore, we examined the possibility that laboratory data of daily blood examination become novel biomarkers. Laboratory data of 16 melanoma patients who were treated with nivolumab were retrospectively analyzed. Patients were classified as responder group or non-responder group. Examined were: white blood cell count (WBC), absolute lymphocyte counts (ALC), absolute neutrophil count (ANC), absolute monocyte count (AMC), absolute eosinophil count (AEC), and absolute basophil count (ABC), as well as levels of lactate dehydrogenase (LDH), C-reactive protein (CRP), one hour value of erythrocyte sedimentation rate (ESR), and 5-S-cysteinydopa (5-S-CD). Responder group showed significantly higher baseline levels of ESR or CRP and significantly lower ALC level before nivolumab treatment. Additionally, nivolumab treatment decreased the levels of CRP, ESR, and ANC, while it increased ALC level in the responder group. CRP was the most effective in distinguishing responder group from non-responder group both before and during treatment, according to the receiver operating characteristic (ROC) curve. We firstly showed that ESR is also the baseline biomarker of the efficacy of nivolumab. Furthermore, we confirmed that CRP is useful to predict the efficacy both before and during the treatment, and suggested that CRP is the most effective biomarker among daily blood examination by using ROC curve analysis. There is a possibility that nivolumab treatment may be more effective for malignant melanoma with stronger inflammation.

The Clinical and Histological Effect of a Low-Fluence Q-Switched 1,064-nm Neodymium: Yttrium-Aluminum-Garnet Laser for the Treatment of Melasma and Solar Lentigenes in Asians: Prospective, Randomized, and Split-Face Comparative Study.

BACKGROUND: The low-fluence Q-switched 1,064-nm neodymium:yttrium-aluminum-garnet laser (QSNYL) is popular for melasma treatment among Asians. OBJECTIVE: This study was to evaluate the clinical and histological effects of the low-fluence QSNYL for treatment of melasma and solar lentigenes. MATERIALS AND METHODS: In this randomized split-face clinical study, 22 patients with melasma or solar lentigo received low-fluence QSNYL weekly for 10 sessions on one cheek. The treatment efficacy was determined by Mexameter skin colorimetry, physician and patient assessment, and by evaluating histological changes. RESULTS: The treated sides had statistically significant reductions in the melanin and erythema indices (EI); 50.0% of melasma and 62.5% of solar lentigo patients had >50% clearance after the final treatment. The increased EI, vascularity, and mast cell activity in patients with melasma and large-sized solar lentigo showed no improvement. The recurrence rates were 16.7% and 12.7% for melasma and solar lentigo, respectively. Postinflammatory hyperpigmentation developed in 1 patient, but no serious side effects were noted. CONCLUSION: Low-fluence QSNYL is effective in treating melasma and small type solar lentigo in Asians. The authors' study also demonstrated that lesion thickness, vascularity, and mast cell activity can be used to predict the efficacy of the treatment of these lesions.

Long-Term Clinical and Histological Effects of a Bipolar Fractional Radiofrequency System in the Treatment of Facial Atrophic Acne Scars and Acne Vulgaris in Japanese Patients: A Series of Eight Cases.

OBJECTIVE: This retrospective case series was designed to compare the long-term safety and efficacy of bipolar fractional radiofrequency (FRF) therapy as a treatment for atrophic acne scars (ASs) and acne vulgaris. BACKGROUND DATA: Few clinical and histological studies have examined the long-term utility of bipolar FRF therapy as a treatment for ASs and acne in people with darker skin. MATERIALS AND METHODS: Eight Japanese patients with ASs and mild-to-severe acne on both cheeks were treated with a bipolar FRF system (eMatrix; Syneron). Five treatment sessions with the same settings (coverage rate: 10%; peak energy: 62 mJ/pin; two passes) were carried out at 1-month intervals, and the patients were followed up for at least 1 year after the final treatment. Assessments of ASs and acne severity were performed and samples were removed for histological examination. RESULTS: We demonstrated that mild ASs responded better than moderate and severe ASs, and at least 50% improvement in scar severity was seen in 50% of patients after the final treatment. Six patients remained disease free at 1.5 years without the use of any additional therapies. The biopsy specimens showed a marked improvement characterized by a decrease in dermal pilosebaceous units and perivascular inflammatory cell infiltrates with an increase in elastin content and collagen deposition in the upper dermis. CONCLUSIONS: Bipolar FRF treatment showed long-term effectiveness against mild ASs and acne in Asian patients and had minimal side effects.

Clinical studies of the treatment of facial atrophic acne scars and acne with a bipolar fractional radiofrequency system.

Few clinical studies have examined the utility of bipolar fractional radiofrequency (FRF) therapy as a treatment for atrophic acne scars and active acne in people with darker skin. This study was designed to compare the safety and efficacy of bipolar FRF therapy as a treatment for atrophic acne scars and acne vulgaris. Twenty-three Japanese patients with atrophic acne scars and mild to severe acne on both cheeks were treated with a bipolar FRF system (eMatrix; Syneron, Yokneam Illit, Israel). Five treatment sessions were carried out at 1-month intervals, and the patients were followed up for 3 months after the final treatment. Assessments of scar severity and the number of acne lesions and 3-D in vivo imaging analysis were performed. Evaluations of the treatment outcomes and their effects on the patients' quality of life (QOL) were also carried out. We demonstrated that the improvement in scar volume was marked in the patients with mild scars and was at least moderate in 23 (57.5%) of the treated areas. With regard to the number of acne lesions, the treated areas exhibited significantly fewer lesions compared with the baseline at each time point (P < 0.05). The patients' assessments of the treatment outcomes and their QOL indicated that both had improved significantly by the end of the study. Furthermore, significant reductions in the patients' sebum levels, skin roughness and scar depth were observed. Bipolar FRF treatment significantly improved the atrophic acne scars and acne of Japanese patients and had minimal side-effects.

Disseminated cryptococcosis-induced skin ulcers in a patient with autoimmune hepatitis.

We report the case of a 68-year-old woman with autoimmune hepatitis (AIH) who had leg ulcers induced by disseminated cryptococcosis. She had received prednisolone for her AIH at 20 mg/day for maintenance. On the initial visit, she complained of a painful ulcer that had round, shallow pockets with erythema and erythematous subcutaneous indurations on the right thigh. Several metacarpophalangeal joints and wrist joints were swollen, with tenderness and stiffness in the morning for over 3 h. Her serum rheumatoid factor was high. Since other autoimmune disorders such as rheumatoid arthritis can present with AIH, it was necessary to distinguish it from ulcers due to rheumatoid arthritis, although the characteristic features of these ulcers seemed to be different. A biopsy specimen from the erythematous skin showed globe-shaped organisms in the dermis and subcutaneous tissues; vasculitis and phlebostasis were not observed. The results from computed tomography scans and sputum culture led to the diagnosis of disseminated cryptococcosis. The administration of fluconazole, fosfluconazole, and voriconazole for about 2 months improved the cryptococcal pneumonia, but the size of the skin ulcer enlarged. The administration was changed to itraconazole, which reduced the size. Cryptococcal infections occur more commonly in immunocompromised hosts, including patients under immunosuppressive therapies such as corticosteroids. The possibility that the skin ulcers in immunocompromised hosts may be caused by cryptococcosis should be considered.

Clinical evaluation of glycolic acid chemical peeling in patients with acne vulgaris: a randomized, double-blind, placebo-controlled, split-face comparative study.

BACKGROUND: Glycolic acid (GA) peels are frequently performed as adjuvants to the treatment of facial acne. There have been few clinical trials reported of GA peels for acne in people with darker skin. OBJECTIVES: To determine the safety and efficacy of GA peels in the treatment of moderate acne vulgaris in Asian skin. METHODS: In this prospective, randomized, double-blind, placebo-controlled, split-face clinical trial, 26 patients with moderate acne were treated with 40% GA (pH 2.0) on half of the face and placebo on the other half. The procedure was performed five times at 2-week intervals. RESULTS: The GA sides had statistically significant reductions in acne lesions at each time point from baseline values. There were statistically significant differences between the GA and placebo sides. The GA sides had better responses for noninflammatory lesions than for inflammatory lesions. In bioengineering measurements, sebum levels were statistically significantly reduced after the initiation of therapy on both sides at weeks 8 and 10, but there were no statistically significant differences between the two sides. CONCLUSION: Forty percent GA peels significantly improved moderate acne in this study. It is effective and safe in Asians.

Chemokine receptor CXCR4 is a novel marker for the progression of cutaneous malignant melanomas.

The CXCR4/CXCL12 pathway has recently been reported to be involved in stimulating the metastasis of many different neoplasms, in which CXCR4 activates various phenomena such as chemotaxis, invasion, angiogenesis and proliferation. The purpose of this study was to analyze a possible association between the expression of chemokine receptors CXCR4, CCR6 and CCR7 with the clinicopathological features of cutaneous malignant melanoma, and to assess the usefulness of these chemokine receptors for diagnosis and prognosis. In our study, a percentage of immunoexpression of both CXCR4 and its ligands CXCL12 was associated with high clinical risk. In contrast, the patients with a low immunoexpression of CXCR4 and CXCL12 had low clinical risk. CCR6 and CCR7 immunoexpressions were also correlated with some clinical parameters, but seemed no more useful than CXCR4. These data suggest that the assessment of CXCR4 immunoexpression is a novel tool for predicting tumor aggressiveness in malignant melanomas, and in particular, a high immunoexpression percentage of CXCR4 and CXCL12 might be a sign of a poor prognosis.

Severe ulceration with impaired induction of growth factors and cytokines in keratinocytes after trichloroacetic acid application on TRPV1-deficient mice.

Transient receptor potential vanilloid 1 (TRPV1) is a highly polymodal TRP channel activated by various stimuli, including capsaicin, heat and acids. TRPV1 expression can be detected widely but is highest in sensory neurons and its activation alerts the body to noxious signals via neurogenic pain. Although TRPV1 is reportedly localized in the epidermis, it remains unclear how TRPV1 is involved in the chemical peeling processes with cytotoxic acids. Therefore, in this study, the role of TRPV1 on the effects of trichloroacetic acid (TCA) peeling was assessed using TRPV1-deficient mice. Following the confirmation of TRPV1 expression in murine keratinocytes with reverse transcription-polymerase chain reaction and immunohistochemistry, the effects of TCA on TRPV1-deficient mouse skin were compared with those on wild-type mouse skin. Our results indicated that TRPV1 expression was not required for TCA-induced DNA damage, as shown by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, but was indispensable for the TCA-induced production of distinct growth factors and cytokines by keratinocytes. Ulceration after TCA peeling was actually more severe in the absence of TRPV1, suggesting that the TRPV1-mediated epidermal production of growth factors and cytokines affected the damaging and healing processes of TCA-peeled skin to induce rejuvenation.

Two patterns of solar lentigines: a histopathological analysis of 40 Japanese women.

Solar lentigines are common acquired pigmented lesions on sun-exposed skin. Their histopathological features have been reported as large numbers of melanocytes at the base of clubbed and budding rete ridges. In this study, biopsies were taken from facial solar lentigines in 40 Japanese women, and the sections were stained using hematoxylin-eosin, Fontana-Masson, and immunostained for melanocytes and Langerhans cells in order to verify the histological patterns of Japanese patients. We characterized the histopathological features of solar lentigines on the face and identified two patterns: one pattern (20/40 cases) demonstrated a flattened epidermis with basal melanosis, and the other pattern (20/40 cases) showed epidermal hyperplasia with elongated rete ridges composed of deeply pigmented basaloid cells. We termed the former pattern the "flattened epidermis" group, and the latter the "budding" group, respectively. The flattened epidermis group showed a significantly thinner epidermis, more severe solar elastosis and fewer Langerhans cells in the epidermis as compared with the budding group. We concluded that more severely sun-damaged solar lentigines might show the changes observed in the flattened epidermis group. Langerhans cells in the epidermis of solar lentigines might play a role in the remission of postinflammatory pigmentation due to aesthetic treatment.

Phenol application to angiosarcomas: implications and histologic studies.

BACKGROUND: Cutaneous angiosarcoma (AS) is an aggressive endothelial sarcoma that arises in elderly people. Effective treatment options are limited. Phenol application has been reported to be effective and economical. AIMS: To evaluate the efficacy of phenol application for the treatment of AS, and to examine the histologic changes in three cases of cutaneous AS with phenol application. METHODS: After phenol application, biopsy specimens were collected from three patients with cutaneous AS. Paraffin-embedded sections of the skin specimens were then stained with hematoxylin and eosin. The detection of apoptosis was performed using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL) method, and the depth of TUNEL-positive cell staining was examined. RESULTS: Phenol treatment induced a strong degeneration of tumor cells and endothelial cells in the dermis, when compared with nontreated areas. Positive staining of tumor cells and/or endothelial cells by the TUNEL method was found in phenol-treated lesions, but not in nontreated lesions. The injurious effects on these tumor cells persisted for as long as 6 h after phenol application. CONCLUSION: From a comparison of noninvasive therapy with standard surgical therapy, it is obvious that phenol peeling has several advantages with regard to the ease of the procedure, time efficiency, no need for special equipment, low therapeutic costs, good pain control, and post-treatment follow-up. This study suggests that phenol application can be a supportive treatment for AS.