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Background The American Joint Committee on Cancer (AJCC) 8th Edition Cancer Staging System was implemented in 2018; however, it has not been validated in an Asian melanoma population. Objective The purpose of this study was to validate the new system using a cohort of Japanese melanoma patients. Methods The AJCC 7th and 8th Editions were used for TNM classification of patients in a database established by the Japanese Melanoma Study Group. Patient data with sufficient information to be applicable to the AJCC 8th staging were selected. The Kaplan–Meier method was used to estimate disease-specific survival and relapse-free survival. Results In total, data for 3097 patients were analyzed. The 5-year disease-specific survival according to the 7th and 8th Edition staging system were as follows: IA = 98.5%/97.9%; IB = 95.4%/96.2%; IIA = 94.2%/94.1%; IIB = 84.6%/84.4%; IIC = 72.2%/72.2%; IIIA = 76.2%/87.5%; IIIB = 60.7%/72.6%; IIIC = 42.0%/55.3% and IIID = none/26.0%. The 5-year relapse-free survival according to the 7th and 8th Edition staging was as follows: IA = 94.5%/92.7%; IB = 85.4%/85.3%; IIA = 80.1%/79.4%; IIB = 71.4%/70.6%; IIC = 56.8%/55.7%; IIIA = 56.8%/69.4%; IIIB = 42.6%/56.8%; IIIC = 20.0%/33.3% and IIID = none/6.5%. Conclusion The results show that new staging system could efficiently classify our Japanese melanoma cohort. Although there was no difference in Stage I and II disease between the 7th and 8th Edition systems, we should be careful in managing Stage III disease since the survival curves of the 8th Edition staging were completely different from the 7th Edition. Moreover, our results indicate that adjuvant therapies for Stage IIB and IIC should be developed, since the relapse-free survival for these stages were equivalent to Stage IIIA and IIIB, respectively.

Background The incidence of melanoma among those of an Asian ethnicity is lower than in Caucasians; few large-scale Asian studies that include follow-up data have been reported. Objectives To investigate the clinical characteristics of Japanese patients with melanoma and to evaluate the prognostic factors. Methods Detailed patient information was collected from the database of Japanese Melanoma Study Group of the Japanese Skin Cancer Society. The American Joint Committee on Cancer seventh Edition system was used for TNM classification. The Kaplan-Meier method and Cox proportional hazards model were used to estimate the impact of clinical and histological parameters on disease-specific survival in patients with invasive melanoma. Results In total, 4594 patients were included in this analysis. The most common clinical type was acral lentiginous melanoma (40.4%) followed by superficial spreading melanoma (20.5%), nodular melanoma (10.0%), mucosal melanoma (9.5%), and lentigo maligna melanoma (8.1%). The 5-year disease-specific survival for each stage was as follows: IA = 98.0%, IB = 93.9%, IIA = 94.8%, IIB = 82.4%, IIC = 71.8%, IIIA = 75.0%, IIIB = 61.3%, IIIC = 41.7%, and IV = 17.7%. Although multivariate analysis showed that clinical classifications were not associated with survival across all stages, acral type was an independent poor prognostic factor in stage IIIA. Conclusions Our study revealed the characteristics of melanoma in the Japanese population. The 5-year disease-specific survival of each stage showed a similar trend to that of Caucasians. While clinical classification was not associated with survival in any stages, acral type was associated with poor survival in stage IIIA. Our result might indicate the aggressiveness of acral type in certain populations.

LETTER TO THE EDITOR

Accumulating evidence suggests that psoriasis is frequently accompanied by metabolic disorders, such as obesity and diabetes. However, the mechanisms underlying the association between increased psoriasis severity and concomitant metabolic syndrome have not been fully clarified. Herein, we show that imiquimod-induced psoriasiform inflammation was exacerbated and prolonged in diabetic obese mice compared to that in control mice, accompanied by remarkably increased lesional expressions of Cxcl5 and Il-1b. Notably, a large number of CXCL5+ Ly6G+ cells infiltrated the dermis and subcutaneous fat tissue of the diabetic obese mice. Most macrophages in the subcutaneous fat tissues of the diabetic obese mice were positive for expression of IL-1β and GRP78/Bip, an endoplasmic reticulum stress marker. Depletion of Ly6G+ cells and macrophages diminished the imiquimod-induced psoriasiform inflammation. Further, CXCL5 potentiated the secretion of IL-1β from macrophages and palmitic acid, a fatty acid released from subcutaneous adipocytes, further enhanced IL-1β secretion via endoplasmic reticulum stress induction. Combined with the fact that the serum levels of both CXCL5 and palmitic acid are significantly elevated in patients with metabolic syndrome, our results suggest a role for CXCL5 and endoplasmic reticulum stress in the increase of psoriasis severity of patients with concomitant metabolic syndrome.

The interleukin (IL)-23/IL-17 axis is strongly implicated in the pathogenesis of psoriasis. Previous studies showed that IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index. However, the mechanism whereby IL-18 affects disease severity remains unknown. In this study, we investigated the effects of IL-18 on a psoriasis-like skin inflammation model induced by recombinant mouse IL-23. We found that IL-18, cooperatively with IL-23, induced prominent inflammation and enhanced psoriasis-like epidermal hyperplasia. In the skin of mice treated with IL-23 plus IL-18, the expression of interferon-γ was significantly upregulated and that of chemokine (C-X-C motif) ligand 9 (CXCL9) was synergistically increased. Histologically, strong positive signals of CXCL9 were observed around the infiltrating inflammatory cells. The current results suggest that IL-18 might synergize with IL-23 to induce a T helper 1 immune reaction, without inhibiting the IL-23/IL-17 axis, and thus may aggravate psoriatic inflammation.

Fibroblastic connective tissue nevus (FCTN) is a benign cutaneous mesenchymal lesion characterized by proliferation of CD34-positive fibroblastic/myofibroblastic spindle-shaped cells. We report a case of agminated FCTN on the right lower abdomen of a 1-year-old boy.

Dipeptidyl peptidase-4 inhibitors are a new class of antidiabetic agents also shown to possess immunomodulatory functions. Although various dipeptidyl peptidase-4 inhibitors have been widely used and assumed to be administrated in many patients with psoriasis accompanied by type 2 diabetic mellitus, only two studies have shown that sitagliptin, a dipeptidyl peptidase-4 inhibitor, improved the cutaneous symptom of psoriasis independently of its antihyperglycemic effect. We report two cases of psoriatic skin lesions that obviously ameliorated after initiation of therapy with teneligliptin, a novel dipeptidyl peptidase-4 inhibitor. This report strengthens the notion that dipeptidyl peptidase-4 inhibitors clinically exert an ameliorating effect on psoriatic lesions. Considering the pharmacokinetic data that indicate the high penetrative ability of teneligliptin into skin tissue, teneligliptin may be considered an effective agent for improving skin lesions of psoriasis.

Skin cancer incidence rates are continuing to rise; however, if detected at an early stage, they can be cured with minimally invasive treatment. Therefore, the identification of novel and robust biomarkers for the early detection of skin cancer is required to improve the quality of life of the patient after treatment. In the present study, we aimed to identify novel biomarkers of skin cancers. We carried out serum metabolomics using gas chromatography/triple quadrupole mass spectrometry for two types of skin cancer: squamous cell carcinoma and melanoma. The changes in the expression of metabolites compared with healthy volunteers were analyzed by principal component analysis. Among all 118 metabolites, 27 in patients with squamous cell carcinoma and 33 in patients with melanoma showed significant changes in comparison with healthy volunteers. Principal component analysis showed that both skin cancer groups could be distinguished from the healthy volunteers group. We further investigated the specific metabolites most useful for these distinctions. In the squamous cell carcinoma group, these metabolites were glycerol, 4-hydroxybenzoic acid, sebacic acid, fucose and suberic acid. In the melanoma group, these metabolites were glutamic acid, sebacic acid, suberic acid, 4-hydroxybenzoic acid and phenylalanine. The present study identified several metabolites that were distinct for certain skin cancer types, which could potentially be used as diagnostic biomarkers leading to novel clinical management strategies.

Cytomegalovirus (CMV) is a DNA virus belonging to the Herpesviridae family, which causes various diseases with diverse symptoms, such as pneumonia, hepatitis, meningitis, retinitis, gastrointestinal ulcers, and cutaneous ulcers, especially in immunocompromised patients. CMV-related cutaneous ulcers often develop in the anogenital region and occasionally cause life-threatening complications. We report two patients with CMV-related cutaneous ulcers indicating an ominous clinical prognosis and severe [...]

Cutaneous angiosarcoma is an aggressive neoplasm that frequently metastasizes to the lungs, a characteristic closely associated with high mortality [1]. Although several chemotherapeutic regimens have been tried, lung metastasis is uncontrollable in almost all cases [2]. We present a case of cutaneous angiosarcoma in which the pulmonary metastasis showed a complete response (CR) to pazopanib treatment. The tumor had a mutation in the transmembrane domain of KIT.A 77-year-old man presented with a [...]

The therapeutic strategies for metastatic melanoma have dramatically changed. Nivolumab, a human monoclonal antibody against programmed cell death 1 (PD-1) and vemurafenib, a selective BRAF inhibitor, have shown clinical efficacy [1, 2]. Although new therapies exist, no consensus on their optimal combination yet exists. Brain metastasis is frequent in patients with advanced melanoma, resulting in poor prognosis, and the median overall survival of these patients is approximately four months [3]. [...]

Malignant melanoma has been considered a prototypical ‘immunogenic’ tumor through clinical observations, such as the spontaneous regression of primary lesions, their higher incidence in immune-suppressed individuals, and the development of vitiligo after immunotherapy. Among many cytokines, IL-12 is one of the best characterized and the most potent anti-tumor cytokines. Although the systemic application of IL-12 resulted in disappointing results owing to its considerable toxicity, IL-12 is not entirely unusable in the clinical setting. IL-12-related cytokines, IL-23 and IL-27, have also been shown to possess anti-tumor activities in preclinical models. Although belonging to the same cytokine family, IL-12, IL-23 and IL-27 were found to have different anti-tumor mechanisms, adjuvant activity for tumor vaccines and adverse effects in a poorly immunogeneic melanoma model. In addition, their novel activities on melanoma have been clarified. We briefly review the key features of these members of the IL-12 cytokine family and discuss their potential relevance to melanoma immunity and antimelanoma immunotherapy.

68歳男性。2003年5月中旬より右腎部に腫瘤を自覚し, 右鼠径部にリンパ節が腫脹してきたので2003年6月23日当科を受診した。初診時3.4×3.7cm大で弾性硬の紅褐色皮下腫瘤を呈し, 生検にてメルケル細胞癌と診断した。2003年7月30日広範囲切除, 右鼠径・外腸骨リンパ節郭清術を施行し, 右鼠径部リンパ節転移を認めたため, 術後放射線療法を追加した。その後再発転移なく経過したが, 2005年4月血清NSE値が上昇し, CT上で多発肝転移像を認めた。エトポシド・シスプラチン療法は効果なく, シクロフォスファミド・ドキソルビシン・ビンクリスチン療法が著効し, 一旦CRとなった。しかし, 10月に肝転移が再発し, 胸腔内転移も認め, アムルビシンを投与するも効果なく, 2005年12月永眠された。多発肝転移を来した症例で, 化学療法の選択に難渋した。

The purpose of the current study is to establish the dynamic close-mouth view radiograph method. Seven healthy volunteers were enrolled. Dynamic open-mouth and close-mouth view radiographs were obtained. The odontoid lateral mass interval and the dynamic atlantodental lateral shift (ADLS) were measured. The ADLS was 9.4+/-5.3% by the close-mouth view, showing a significantly greater percentage than that of 5.3+/-4.0% by the open-mouth view. The dynamic close-mouth view can be useful for diagnosis of atlantoaxial lateral instability.

A method for the selection of appropriate test case, an important issue for conformance testing of protocol implementations as well as software engineering, is presented. Called the partial W-method, it is shown to have general applicability, full fault-detection power, and yields shorter test suites than the W-method. Various other issues that have an impact on the selection of a suitable test suite including the consideration of interaction parameters, various test architectures for protocol testing and the fact that many specifications do not satisfy the assumptions made by most test selection methods (such as complete definition, a correctly implemented reset function, a limited number of states in the implementation, and determinism), are discussed. >

The purpose of this study is to calculate the relationship between the circular shape of a corrugated waveguide and its electrical transfer characteristics by the finite-difference time-domain (FDTD) method. To improve the waveguide to transport with a lower loss of energy than the previous design, we optimize the waveguide structure by the time evolution of the electromagnetic fields in the waveguide. However, the calculation in a 3D model is difficult because of the large data size and the long calculation run time. Therefore, we used a cylindrical symmetry model. As a result of this simulation, a correlation of the electromagnetic field in the input source position and the output position has been calculated.

When we design and construct a large-scale device, it is very important to confirm the interference among its parts. We might need to confirm not only the interference among the parts that are designed at the start but also the interference with some parts that are added after construction. However, sometimes even on using 3D CAD, we cannot detect the interference or the collision among parts, particularly when these parts form a complex 3D shape. On the other hand, virtual reality devices have been used in various fields such as design support systems; however, real-time collision detection among complex parts has been difficult to achieve. We constructed a system that can detect collision and interference in real time in a virtual reality system. This engine can detect interference between polygons. This enables to calculate more accurately than voxel-based detection engine. Moreover, we propose a dynamic interference vector for removing interference. This vector is defined as a local minimum vector which removes the interference from the same edge where the contact starts. This method enables to prevent an object moves discontinuously, when the interference is removed. Finally, we introduced an example of using this system for assembling parts.