Masaki Otsuka

Survival rates and prognostic factors of Epstein-Barr virus-associated hydroa vacciniforme and hypersensitivity to mosquito bites.

Epstein‐Barr virus (EBV)‐associated T/natural‐killer lymphoproliferative disorders form a group of diseases that includes classical and systemic hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). Patients with systemic HV (sHV) and HMB often have a poor prognosis, although little is known about the prognostic factors.

Efficacy and safety of nivolumab in Japanese patients with previously untreated advanced melanoma: A phase II study

Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T‐cell activation through overexpression of the inhibitory receptor programmed death 1 (PD‐1) ligands. The PD‐1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has shown promising anticancer activity in various cancers. We carried out a single‐arm, open‐label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma. Twenty‐four patients with stage III/IV or recurrent melanoma were enrolled and received i.v. nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was overall response rate evaluated by an independent radiology review committee. The independent radiology review committee‐assessed overall response rate was 34.8% (90% confidence interval, 20.8–51.9), and the overall survival rate at 18 months was 56.5% (90% confidence interval, 38.0–71.4). Treatment‐related adverse events (AEs) of grade 3 or 4 only occurred in three patients (12.5%). Two patients discontinued nivolumab because of AEs, but all AEs were considered manageable by early diagnosis and appropriate treatment. Subgroup analyses showed that nivolumab was clinically beneficial and tolerable regardless of BRAF genotype, and that patients with treatment‐related select AEs and with vitiligo showed tendency for better survival. In conclusion, nivolumab showed favorable efficacy and safety profiles in Japanese patients with advanced or recurrent melanoma, with or without BRAF mutations. (Trial registration no. JapicCTI‐142533.)

Increase of DC-LAMP+ mature dendritic cell subsets in dermatopathic lymphadenitis of mycosis fungoides

BackgroundLittle is known about the immunological milieu of the skin-draining lymph nodes (LNs) in mycosis fungoides (MF).ObjectivesWe studied dendritic cell (DC) subsets in the dermatopathic lymphadenitis of MF patients.MethodsWe immunohistochemically examined DC subsets and their distribution in 16 LN samples from 14 patients with MF (N1 LN, eight patients; N2, four; and N3, four), and we compared them with non-metastatic sentinel LNs from eight patients with melanoma.ResultsThe number of S-100 protein+ DCs was markedly increased in the LNs from the MF patients and the major component was DC-LAMP+ mature DCs in the outer and paracortex areas, where DC-SIGN+ immature DCs were relatively decreased in proportion. In contrast, DC-SIGN+ cells were relatively increased in proportion compared to DC-LAMP+ cells in the medulla. Although no significant difference was observed in the proportions of CD1a+ or Langerin+ DCs among the N1, N2, and N3 nodes, CD163+ M2-type macrophages were increased in number in the N2 and N3 nodes.ConclusionsOur observations indicate that mature DCs accumulate in the outer and paracortex areas in dermatopathic lymphadenitis and M2-type macrophages might increase in number during disease progression.

Primary signet‐ring cell/histiocytoid carcinoma of the axilla expressing human epidermal growth factor receptor 2

residues and sugar chain structures. Besides “natural’’ IFN-b, local injections of “recombinant’’ IFN-b (rIFN-b) are currently used to treat multiple sclerosis (MS). rIFN-b has structural variants, 1a and 1b. The differences in these IFN variants are shown in Table 1. rIFN-b sometimes induces local reactions including redness, pain, and occasionally, skin ulcers. Further, it has been reported that s.c. injections of IFN-a used to treat MM can also cause skin ulcers at the injection sites. The pathogenic mechanisms underlying skin ulcers induced by IFN injections remain unclear. Previous published work has indicated that some forms of IFN, including rIFN-b, produced direct vasospastic effects on acral skin. This, in combination with the susceptibility of the amputation wound of the toe to skin necrosis, further aided by the site of the injections, could have contributed to skin ulcer development. We could not find any prior reports either in Japanese or English of skin ulcers following nIFN-b injections. According to Daiichi Sankyo (Tokyo, Japan), 300–400 MM patients begin treatment with nIFN-b yearly. In contrast, official patient data from the past 16 years indicate that some 20 000 MS patients annually began treatment with rIFN-B-1a worldwide. The relative scarcity of nIFN-b use in comparison with rIFN-b use may account for the absence of reports concerning nIFN-b-induced skin ulcers. The present paper may be the first report of skin ulcers following local injections of nIFN-b. However, such cases may in fact have hitherto simply been unreported.

Surgical management of axillary necrotizing fasciitis: a case report.

Axillary necrotizing fasciitis (NF) is quite rare and requires special management with respect to debridement and delayed surgical reconstruction. A 76‐year‐old man presented to our emergency department with a 2‐day history of high fever, severe left axillary pain and redness. A few hours later, he developed discoloration and hemorrhagic bulla in the axilla, and the redness enlarged on the trunk. Emergency surgical debridement was performed. The blackish necrosis in the axilla was completely excised and the erythematous areas in the chest wall were cut down to the level of the fascia. Split‐thickness skin grafts were applied during the second debridement on the 30th day of hospitalization and negative pressure wound therapy was used. Although the grafts took partially, full thickness axillary defects remained. We performed reconstruction with a pedicled latissimus dorsi flap on day 78. This case highlights some of the important surgical considerations in the management of axillary NF.

Usefulness of serum 5-S-cysteinyl-dopa as a biomarker for predicting prognosis and detecting relapse in patients with advanced stage malignant melanoma.

With the recent development of novel molecular targeted drugs for advanced stage malignant melanoma (MM), including RAF and mitogen‐activated protein kinase kinase inhibitors and immune checkpoint blockers, the early detection of relapse is important for managing patients with MM. In this study, we retrospectively analyzed two conventional serum biomarkers, 5‐S‐cysteinyl‐dopa and lactate dehydrogenase, in patients with MM (n = 140) who were treated at a single Japanese institute from June 2007 to June 2015. At the initial hospital visit, serum 5‐S‐cysteinyl‐dopa levels were significantly increased in patients with stages III (n = 38) and IV (n = 20) MM compared with patients with stages 0–II (n = 62) MM. In addition, in patients with stages III and IV MM, serum 5‐S‐cysteinyl‐dopa levels of more than 15.0 nmol/L at initial hospital visit correlated with a poor prognosis. In 11 of 14 patients whose disease progressed during follow up (mostly from stages III–IV), serum 5‐S‐cysteinyl‐dopa levels exceeded the normal limit of 10.0 nmol/L during the clinical detection of distant metastases. These results indicate the usefulness of measuring serum 5‐S‐cysteinyl‐dopa levels at initial hospital visit and during follow up for early and effective therapeutic interventions using newly developed molecular targeted drugs.

Comparative study on driver mutations in primary and metastatic melanomas at a single Japanese institute: A clue for intra- and inter-tumor heterogeneity

BACKGROUND Searching for driver mutations in melanoma is critical to understanding melanoma genesis, progression and response to therapy. OBJECTIVES We aimed to investigate the frequency and pattern of driver mutations in Japanese primary and metastatic melanomas including cases of unknown primary origin, in relation to their clinicopathologic manifestations. METHODS Seventy-seven samples from 60 patients with melanoma were screened for 70 driver mutations of 20 oncogenes by Sequenom MelaCarta MassARRAY, and the results for primary and metastatic melanomas were compared. RESULTS Of 77 tissue samples, BRAF V600E was detected in 21 samples (27%), CDK4 R24C in 7, EPHB6 G404S in 6, BRAF V600K in 2, NEK10 E379K in 2, and CDK4 R24H, NRAS Q61K, NRAS Q61R, KRAS G12A, KIT L576P, KIT V559A, ERBB4 E452K, and PDGFRA E996K in one sample each. No driver mutations related to the MAPK cascade including RAS and BRAF were detected in the chronically sun-damaged (CSD) group of melanoma. Dual or triple driver mutations were found in four of 40 (10%) samples from the primary melanomas, and three of 37 (8%) of the metastatic melanomas. Fourteen of 26 (54%) samples of non-CSD melanoma, and 3 of 6 (50%) melanomas of unknown primary origin had the BRAF V600E mutation. Mutations in membrane-bound receptors including KIT, ERBB4 and EPHB6 were detected in 8 of 77 (10%) samples. Of 17 pairs of primary and metastatic melanomas from the same patient, the primary mutation pattern was changed to a novel one in three cases, and only one of the plural mutations in the primary melanoma was found in the metastatic lesions in two cases. CONCLUSIONS BRAF V600E is a predominant mutation in non-CSD melanoma and melanomas of unknown primary origin. Mutational heterogeneity may exist in the primary melanoma (intra-tumor heterogeneity), and between the primary and metastatic lesions (inter-tumor heterogeneity).

Beneficial effects of neutrophil-targeted therapy for pyoderma gangrenosum associated with ulcerative colitis

ejd.2011.1461 Auteur(s) : Kazuko Ikeda, Toshihisa Hamada t-hamada@cc.okayama-u.ac.jp, Masaki Otsuka, Keiji Iwatsuki Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho 2-5-1, 700-8558 Okayama, Japan Pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterized by aseptic ulcers with raised inflammatory borders and dense neutrophilic infiltration throughout the dermis [1]. PG is occasionally associated with ulcerative colitis (UC), rheumatoid arthritis, [...]

Retrospective evaluation of factors influencing successful skin grafting for patients with skin cancer of the foot

Skin grafting is a simple method for reconstruction of a large defect on the foot. Although skin grafting on the foot sometimes fails, it is not clear what factors influence the success rate of skin grafting. We analyzed data for 71 patients with skin cancer of the foot who underwent reconstruction of defects with skin grafting. The factors we evaluated were success rate of skin grafting, weight‐bearing or non‐weight‐bearing area, immediate or delayed reconstruction, and whether a tie‐over bolster was used or not. The success rates were higher in patients with lesions in non‐weight‐bearing areas than in patients with lesions in weight‐bearing areas and in patients who underwent delayed reconstruction than in patients who received immediate reconstruction. On the other hand, the use of a tie‐over bolster did not improve the success rate. In conclusion, delayed reconstruction is desirable if the lesion is located in a weight‐bearing area.

Infectious complications and managements for surgical site infections in genital Paget's disease.

Background  Extramammary Pagets disease is an intra‐epidermal carcinoma that occurs preferentially in genital areas. Patients with genital Pagets disease (GPD) sometimes develop severe post‐surgical infections because of this anatomical disadvantage.