論文 - 宇原　久

Neutrophilic dermatoses with acute myeloid leukemia associated with an increase of serum colony-stimulating factor

Hisashi Uhara, Toshiaki Saida, Hideyuki Nakazawa, Toshiro Ito

Journal of the American Academy of Dermatology   59 ( 2 ) S10 - S12  2008年08月  [査読有り]

　概要を見る

We report a case of acute myeloid leukemia with folliculitis, Sweet's syndrome, and neutrophilic panniculitis after remission induction chemotherapy for acute myeloid leukemia. The level of endogenous granulocyte colony-stimulating factor was closely associated with disease activity. © 2008 American Academy of Dermatology, Inc.

DOI PubMed

A case of primary Epstein-Barr virus-associated cutaneous diffuse large B-cell lymphoma unassociated with iatrogenic or endogenous immune dysregulation

Yasutaka Tokuda, Mana Fukushima, Koh Nakazawa, Shinji Oguchi, Yoko Koganehira, Maki Yamaura, Miwako Iijima, Hiroshi Murata, Hisashi Uhara, Minoru Takata, Toshiaki Saida, Tsutomu Katsuyama, Sigeo Nakamura

Journal of Cutaneous Pathology   35 ( 7 ) 666 - 671  2008年07月  [査読有り]

　概要を見る

Cutaneous Epstein-Barr virus (EBV)-associated B-cell lymphoma (EBVBL) in non-immunocompromised patients is very rare. Here, we report a case of cutaneous EBVBL in a 72-year-old Japanese woman without any signs of immunosuppression. She showed repeated high fever and skin eruptions on the face, limbs and palms. Histological diagnosis was diffuse large B-cell lymphoma. EBV infection was detected by in situ hybridization and Southern blotting. Immunostaining for viral proteins showed the patient to be positive for latent membrane protein 1 (LMP-1) and negative for Epstein-Barr virus nuclear antigen-1 (EBNA-2), indicating that a type II latency EBV infection pattern. © Blackwell Munksgaard 2008.

DOI PubMed

メラノーマの原発巣の厚さとセンチネルリンパ節の転移率についての検討

宇原 久, 山本 明史, 清原 祥夫, 斎田 俊明

日本皮膚科学会雑誌 ( Japanese Dermatological Association )  118 ( 14 ) 3083 - 3088  2008年

　概要を見る

［背景］米国のNational Comprehensive Cancer Network（NCCN）やNational Cancer Center（NCI）のガイドラインは，TisあるいはT1a以外のメラノーマ症例にセンチネルリンパ節（SLN）生検（SLNB）を行うよう推奨している．しかし，日本人ではTumor Thickness（TT）とSLNの転移率との関係について，多数症例で十分検討されていない．［目的］TT，潰瘍の有無とSNの転移率との関係を明らかにする．［症例］厚生労働省がん研究助成金15-10（主任研究者：斎田俊明）構成施設中の13施設より集積された359症例．［結果］①TTと転移率（転移陽性症例数/各T分類症例数）の関係は，pTis：0%（0/36），pT1（1 mm以下）：11.3%（6/56），pT2（1.01～2 mm）：21.0%（13/63），pT3（2.01～4.0 mm）：34.0%（35/103），pT4（4.01 mm以上）：62.4%（63/101）．②T1でSLNに転移を認めた6例中2例はT1b（潰瘍あり）で，残り4例のT1a症例のTTは1.0，0.8，0.55，0.50 mmであった．③TTが4 mm超の症例におけるTTとSLN転移率は，4.01～5 mm：40.0%，5.01～6 mm：57.9%，6.01～7 mm：53.8%，7.01～8 mm：62.5%，8.01～9 mm：87.5%，9.01～10 mm：87.5%，10 mm超：72.0%であった．④T1～T4群，T1～T3群では潰瘍をともなうとSLNの転移率が高くなり，統計学的に有意差を認めた（p<0.001）．［結論］TTの厚い症例では，予測されるSLN転移率と血行性転移率，SLNの存在部位（生検の困難さ）を考慮した上でSLNBの適応を決める必要があると思われる．また，T1a症例に対するSLNBの適応条件についてはさらに検討が必要である．

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A pilot study of human interferon β gene therapy for patients with advanced melanoma by in vivo transduction using cationic liposomes

Kazuhiko Matsumoto, Hitomi Kubo, Hiroshi Murata, Hisashi Uhara, Minoru Takata, Shinichi Shibata, Satoshi Yasue, Akihiro Sakakibara, Yasushi Tomita, Toshiro Kageshita, Yutaka Kawakami, Masaaki Mizuno, Jun Yoshida, Toshiaki Saida

Japanese Journal of Clinical Oncology ( Oxford University Press )  38 ( 12 ) 849 - 856  2008年  [査読有り]

　概要を見る

Background: Cationic liposomes containing the human interferon β (HuIFNβ) gene (IAB-1) was used for the clinical trial for glioma patients. HuIFNβ gene therapy showed much higher anti-tumor activity compared with the administration of HuIFNβ protein for melanoma. These results suggest that HuIFNβ gene therapy is an attractive strategy for the treatment of melanoma. Methods: Stage IV or III melanoma patients with cutaneous or subcutaneous metastatic lesions were enrolled in this pilot study. IAB-1 was dissolved by sterile PBS at a concentration of 30 μg DNA/ml and was injected into cutaneous or subcutaneous metastatic nodules three times a week for 2 weeks and the effect on the injected and non-injected metastatic lesions was evaluated. Results: Clinical responses were as follows (five patients): mixed response (MR) and no change in each one patient, and progressive disease in three patients. In the MR patient, the IAB-1 injected lesion disappeared clinically and histopathologically and one-half of IAB-1 non-injected skin metastases were transiently inflamed and mostly regressed. In the responded non-injected lesions of this patient, histopathologically, infiltration of CD4 positive T cells was observed around the melanoma cells in the dermis, which expressed the HLA-Class II antigen. Adverse events due to this gene therapy were not recognized in any of the patients. Conclusions: The efficacy of this gene therapy was generally insufficient however, some immunological responses were recognized in one patient. No adverse events were observed. HuIFNβ gene therapy could be an attractive strategy for treatment of a variety of malignancies, including melanoma, though some modifications should be required. © The Author (2008). Published by Oxford University Press. All rights reserved.

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Multiple hypersonographic spots in basal cell carcinoma

Hisashi Uhara, Koichi Hayashi, Hiroshi Koga, Toshiaki Saida

Dermatologic Surgery   33 ( 10 ) 1215 - 1219  2007年10月  [査読有り]

　概要を見る

BACKGROUND: High-frequency ultrasound is a useful method to obtain preoperative information regarding extension of basal cell carcinoma. Its contribution to diagnosis is generally limited, however. Recently, we observed hypersonographic spots in some cases of basal cell carcinoma. OBJECTIVE: The present study was performed to determine the diagnostic value of this finding in this type of tumor. MATERIALS AND METHODS: We conducted a retrospective study of archived sonographic images with a 30- or 15-MHz scanner and histology specimens of a total of 85 lesions, consisting of 29 basal cell carcinomas and 56 melanomas. RESULTS: The findings were classified into four patterns as follows: Type A, multiple (more than five spots/lesion) hypersonographic spots (14 cases, 48%) Type B, sparse (3-5 spots/lesion) hypersonographic spots (7 cases, 24%) Type C, multiple moderate sonographic spots (3 cases, 10%) and Type D, sparse moderate sonographic spots (5 cases, 17%). Three of 56 melanoma lesions examined as controls showed the Type D pattern, but none showed Type A, B, or C patterns. Histopathologically, these hypersonographic spots in BCCs seemed to correspond to calcification, horn cysts, or clusters of apoptotic cells in the centers of nests of basal cell carcinoma. CONCLUSION: Multiple hypersonographic spots might become a useful finding for differential diagnosis between basal cell carcinoma and melanoma. © 2007 by the American Society for Dermatologic Surgery, Inc.

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Eccrine porocarcinoma: Clinical and pathological studies of 12 cases

Junko Shiohara, Hiroshi Koga, Hisashi Uhara, Minoru Takata, Toshiaki Saida

Journal of Dermatology   34 ( 8 ) 516 - 522  2007年08月  [査読有り]

　概要を見る

Twelve cases of eccrine porocarcinoma have been reported at our facility in the past 10 years. All of them were Japanese half had lymph node metastases and one-third died of this disease. Lymph node metastasis was correlated with pathological lymphovascular invasion. Death was correlated with a pathological growth pattern and clinical lymph node metastasis. Sentinel lymph node biopsy was performed usefully in two patients. © 2007 Japanese Dermatological Association.

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Estrogen-receptor-alpha-positive extramammary Paget's disease treated with hormonal therapy

M. Iijima, H. Uhara, Y. Ide, S. Sakai, H. Onuma, M. Muto, K. Hayashi, F. Mitsura, S. Kobayashi, A. Yoshizawa, T. Saida

Dermatology   213 ( 2 ) 144 - 146  2006年08月  [査読有り]

　概要を見る

The patient was an 80-year-old man with scrotal and penile extramammary Paget's disease and prostate cancer. Both diseases were in advanced stages. Tumor cells of extramammary Paget's disease strongly expressed estrogen receptor α. The patient was concurrently treated with two kinds of hormonal therapy: the anti-estrogen tamoxifen (20 mg/day orally) for extramammary Paget's disease and the anti-androgen bicalutamide (80 mg/day orally) for prostate cancer. The toxicity of the therapy was mild. All of the metastatic lesions remained stable for 2 months after initiation of dual hormonal therapy. During a follow-up period of 22 months, performance status was well maintained for 17 months. Hormonal therapy may be an alternative for selected cases of advanced extramammary Paget's disease. Copyright © 2006 S. Karger AG.

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【透析と皮膚】臨床例 血栓性微小血管症を伴う高血圧性腎クリーゼを発症した全身性強皮症

古賀 弘志, 宇原 久, 斎田 俊明

皮膚病診療 ( (株)協和企画 )  25 ( 5 ) 533 - 536  2003年05月

　概要を見る

66歳男性.血栓性微小血管症を伴う高血圧性腎クリーゼを発症した全身性強皮症の1例を経験した.高血圧症でカルシウム拮抗剤内服中.両手足のむくみで受診した.両手首,両足首から末梢にび漫性の硬化性浮腫と舌小帯の短縮を認めた.病理組織所見は手背や前腕では汗腺分泌部以下にまで膠原線維が増生し,血管および付属器周囲にリンパ球主体の炎症性細胞浸潤認めた.自己抗体のプロフィールならびにKL-6値の上昇から全身性強皮症と診断し,D-ペニシラミン内服を開始したが,KL-6はさらに上昇し,胸部CTでは右下肺に間質性肺炎像が認められ,皮膚硬化も進行した.その後,クレアチニン値の上昇や腎生検より高血圧性腎クリーゼと診断され,あわせて種々検査から高血圧性腎クリーゼに合併した血栓性微小血管症と診断された.ACE阻害剤による降圧と血液透析,濃厚赤血球輸血とアルブミン,新鮮凍結血漿の輸注で症状は改善した

CD30陽性cutaneous large T cell lymphoma

吉澤 さえ子, 太田 桂子, 宮嵜 敦, 芦田 敦子, 六波羅 詩穂, 宇原 久, 斎田 俊明

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 )  113 ( 5 ) 815 - 815  2003年04月

Lymphangitis of the foot demonstrating lymphatic drainage pathways from the sole

Hisashi Uhara, Toshiaki Saida, Tomomi Watanabe, Yoshihiro Takizawa

Journal of the American Academy of Dermatology ( Mosby Inc. )  47 ( 4 ) 502 - 504  2002年10月  [査読有り]

　概要を見る

Background: There are two main lymphatic routes from the lower extremity: the fibular route to the popliteal node and the tibial route to the distant groin node. However, little is known about lymphatics from the sole. Objective: We attempted to obtain detailed knowledge of the lymphatics from the sole. Methods: Eight patients with lymphangitis were examined and compared with the drainage patterns visualized by blue-dye injection in 7 cases of melanoma. Results: Six lymphangitic streaks started from the lateral edge of the plantar surface, 2 from the heel, and 1 each from the center of the sole and the little toe. All streaks ran to the tibial side and went up along the foot branch of the great saphenous vein. These findings were similar to those of the dye-injected melanoma cases. Conclusion: Lymphangitis makes visualization of lymphatic routes possible and may provide useful information about drainage.

DOI

Evaluation of 5-S-cysteinyldopa as a marker of melanoma progression: 10 years’ experience

Wakamatsu, K, Kageshita, T, Furue, M, Hatta, N, Kiyohara, Y, Nakayama, J, Ono, T, Saida, T, Takata, M, Tsuchida, T, Uhara, H, Yamamoto, A, Yamazaki, N, Naito, A, Ito, S

Melanoma Res. ( LIPPINCOTT WILLIAMS & WILKINS )  12 ( 3 ) 245 - 253  2002年06月  [査読有り]

　概要を見る

5-S-Cysteinyldopa (5-S-CD) has been used as a biochemical marker of melanoma progression. In this study, we measured serum levels of 5-S-CD in 2648 samples taken from 218 patients in order to evaluate the usefulness of this parameter in following melanoma progression and prognosis. 5-S-CD levels were significantly elevated above the upper limit of the normal range (10 nmol/l) in stage IV melanoma patients. The sensitivity of elevated serum 5-S-CD levels in detecting distant metastasis was 73%, while the specificity was 98% and the positive predictive value 94%. The sensitivity was improved to 77% when cases of amelanotic melanoma were excluded. Patients without metastases had elevated 5-S-CD values in 5% of the 1480 serum samples. Changes in serum 5-S-CD levels were followed during disease progression until the end stage in 49 patients. In 33% of the patients, elevation of serum 5-S-CD levels preceded clinical detection of visceral metastases, and in 37% elevation of 5-S-CD levels occurred at the same time as visceral metastasis. Patients with elevated 5-S-CD levels before or after surgical treatment had significantly shorter survival times than those with normal levels. These results show that the level of 5-S-CD in the serum is a sensitive and specific marker in predicting distant metastases. Elevated serum levels of 5-S-CD, before or after surgical treatment, is associated with a poor prognosis. (C) 2002 Lippincott Williams Wilkins.

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Docetaxel induced durable response in advanced extramammary Paget's disease: A case report

S Oguchi, M Kaneko, H Uhara, T Saida

JOURNAL OF DERMATOLOGY ( JAPANESE DERMATOLGICAL ASSOC )  29 ( 1 ) 33 - 37  2002年01月  [査読有り]

　概要を見る

The patient was a 54-year-old Japanese man with a seven-month history of an eroded lesion on the scrotum. Skin biopsy confirmed the diagnosis of extramammary Paget's disease, and a CT scan revealed multiple metastases to the lymph nodes along the iliac artery and aorta. The patient underwent combination chemotherapy with mitomycin C, epirubicin, vincristine, cisplatin, and 5-fluorouracil. After two courses of the regimen, the primary lesions on the scrotum regressed, however, the lymph node metastases did not respond. A regimen of continuous administration of low-dose cisplatin and 5-fluorouracil was not effective for the metastases either. Hence, administration of docetaxel at a dose of 60 mg/m(2)/every four weeks was started. After two courses, the lymph node metastases decreased by 75% compared to the pre-treatment size, and the effect was judged a partial response. The major toxicities were neutropenia, alopecia, pitting edema, and facial erythema, but these were tolerable. Five courses of this regimen were followed by four courses of weekly administration of 25 mg/m(2) docetaxel. The partial response persisted for more than 12 months and the patient was able to enjoy daily life. Docetaxel may be an effective drug for patients with advanced extramammary Paget's disease.

Chemotherapy and chemoimmunotherapy for advanced malignant melanoma

Hisashi Uhara, Toshiaki Saida

Biotherapy   16 ( 3 ) 227 - 232  2002年

　概要を見る

Metastatic melanoma (MM) is resistant to chemotherapeutic agents. Only 10-20% of patients respond to single-drug chemotherapy. Although multi-drug combination chemotherapy increased the response rate to 30-40%, none of these regimens have improved survival compared with dacarbazine alone. Recently, two regimens, the combination of dacarbazine, carmustine, cisplatin and tamoxifen (Dartmouth regimen), and cisplatin/IL-2/interferon alfa-based chemoimmunotherapy, have shown evidence of activity against MM. The response rates were in the range of 40-50% with 10% complete responses. However, randomized studies of these regimens did not show improvement in survival. Recent evaluations of therapeutic regimens for MM are reviewed here.

悪性黒色腫に対する抗がん剤の適正使用ガイドライン(試案)

斎田 俊明, 宇原 久

Skin cancer : official organ of the Japanese Society for Skin Cancer = 皮膚悪性腫瘍研究会機関誌 ( The Japanese Skin Cancer Society )  16 ( 2 ) 158 - 169  2001年10月

　概要を見る

As members of the expert committee of the Japan Society of Clinical Oncology for the proposition of guidelines for cancer chemotherapy, we collected and evaluated relevant literatures of chemotherapy of malignant melanoma. Each literature was critically evaluated using an evaluation form and quality of evidence of each study was classified into 4 grades. Summing up all the available information, recommendation statements were described on several issues concerning chemotherapy of malignant melanoma, and strength of each recommendation was evaluated using standardized criteria. Critical response from readers to this paper is welcomed. [Skin Cancer (Japan) 2001; 16: 158-169]

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進行期悪性黒色腫に対する cisplatin, interleukin-2, interferon β あるいはα併用療法

宇原 久, 斎田 俊明

Skin cancer : official organ of the Japanese Society for Skin Cancer = 皮膚悪性腫瘍研究会機関誌 ( The Japanese Skin Cancer Society )  15 ( 3 ) 309 - 314  2000年12月

　概要を見る

We evaluated efficacy and toxicity of the combination of cisplatin, interleulin-2 (IL-2) and interferon (IFN) α or β in patients with metastatic melanoma. Ten patients received cisplatin, 50 or 80 mg/m² intravenously on day 1, IL-2, 70×10⁴ IU intravenously on days 4-7, 18-22 and IFN β, 300×10⁴ IU subcutaneously or intravenously on every second days (regimen A). Six patients received cisplatin 80 mg/m² intravenously on day 1, IL-2, 140×10⁴ IU subcutaneously on days 2-8 and IFNα, 500×10⁴ IU subcutaneously on days 2, 4, 6, 8 (regimen B). The induction cycle was repeated on day 29 in both regimens. There was no responder in 6 patients (A) and 4 patients (B) assessed for clinical response. Main toxisities were thrombocytopenia, neutropenia, anemia and nausea. Vitiligo-like depigmentation was seen in one patient, whose disease progressed during the therapy. There were no treatment-related death. These regimens had low activities in the treatment of advanced malignant melanoma. [Skin Cancer (Japan) 2000; 15: 309-314]

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Solid facial edema in a patient with rosacea

Hisashi Uhara, Shigeo Kawachi, Toshiaki Saida

Journal of Dermatology ( Japanese Dermatological Association )  27 ( 3 ) 214 - 216  2000年  [査読有り]

　概要を見る

We report a 53-year old man with symmetrical nonpitting edema, conjunctivitis, and acneiform eruptions on the face. Histopathological examination showed perifollicular lymphohistiocytic infiltration and telangiectasias in the upper dermis. Loosely aggregated non-caseating granulomas were scattered through the dermis some of them were seen in the perifollicular regions. The patient was treated with fleroxacin (100 mg/day, orally) for two weeks with a marked reduction of both solid facial edema and periorbital edema.

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進行期悪性黒色腫に対する化学療法・免疫化学療法の最新知見

宇原 久, 斎田 俊明

Skin Cancer ( The Japanese Skin Cancer Society )  14 ( 1 ) 15 - 23  1999年

　概要を見る

Recently developed regimens for the treatment of patients with advanced malignant melanoma were reviewed. Combination chemotherapy of CDDP/BCNU/DTIC/tamoxifen (Dartmouth regimen) and sequential (concurrent) chemoimmunotherapy composed of CDDP based chemotherapy associated with IL-2 and IFN α have been reported to increase overall response rates and CR rates. However, they are still in the clinical trial setting. Temozolomide is an analogue of DTIC that has the advantage of being orally absorbed and crossing into the central nervous system (CNS). Fotemustine, a new nitrosourea, is also active in CNS metastasis. Results of the following two clinical trials of our study group were also described: DAC-Tam therapy using DTIC, ACNU, CDDP and tamoxifen, and sequential biochemotherapy using CDDP, IL-2 and IFN β.

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Immunohistochemical detection of CDK4 and p16(INK4) proteins in cutaneous malignant melanoma

YL Wang, H Uhara, Y Yamazaki, T Nikaido, T Saida

BRITISH JOURNAL OF DERMATOLOGY ( BLACKWELL SCIENCE LTD )  134 ( 2 ) 269 - 275  1996年02月  [査読有り]

　概要を見る

p16(INK4) gene, which encodes a specific inhibitor of cyclin-dependent kinase 4 (CDK4), has been recently reported as an important tumour suppressor gene. It is mapped to chromosome 9p21, which is frequently deleted or mutated in many tumour cell lines including malignant melanoma. Since the CDK4/cyclin D complex propels a cell to go through the G(1) check point of the cell cycle, a critical phase of cell division, alteration of the p16(INK4) gene could lead a cell to uncontrolled proliferation and malignant transformation. To clarify any role for p16(INK4) and CDK4 proteins in the development of human malignant melanoma, we have examined, immunohistochemically, the expression of these two proteins in melanocytic neoplasms including 19 primary lesions of nonfamilial melanoma. Intense nuclear and/or cytoplasmic expression of the CDK4 protein was observed in 11 of 19 cases (58%) of melanoma. In contrast, virtually no nuclear or cytoplasmic staining for CDK4 protein was detected in 28 benign melanocytic naevi, including six Spitz naevi. Expression of p16(INK4) protein was observed in three of 19 melanomas (16%) and in 17 of 28 benign naevi (61%). Inverse expression of CDK4 and p16(INK4), at individual cell level, was detected in one case of melanoma. The present study suggests that CDK4 overexpression is characteristic for malignant melanoma, and probably reflects its autonomous accelerated cell proliferation. The expression rate of p16(INK4) protein in malignant melanoma was lower than that in benign naevi, although the significance of p16(INK4) deletion in melanoma development has not been definitely confirmed.

Expression of α subunit of guanine nucleotide‐binding protein Go in Merkel cell carcinoma

Hisashi Uhara, Yu‐Lai Wang, Sachiyo Matsumoto, Shigeo Kawachi, Toshiaki Saida

Journal of Cutaneous Pathology   22 ( 2 ) 146 - 148  1995年  [査読有り]

　概要を見る

The α subunit of guanine nucleotide‐binding protein Go(Goα), which was initially isolated from bovine brain, interacts with muscarinic cholinergic receptors and regulates neuronal calcium channels. Goα is known to be localized in neural tissues, some endocrine cells, and neuroendocrine tumors. We have immunohistochemically investigated the expression of Goα in 4 cases of Merkel cell carcinoma using the method of microwave treatment. In all cases of Merkel cell carcinoma, Goα was consistently detected on the plasma membrane and cytoplasm of the tumor cells. Nerve fibers in the skin were also positive for Goα, but other epidermal or dermal components such as keratinocytes, melanocytes, fibroblasts, or lymphoid cells were negative. Tumor cells of squamous cell carcinoma, cutaneous lymphoma, sweat gland carcinoma, and malignant melanoma were negative for Go4aL. The present study indicates that Goα may be a useful immunohistochemical marker of Merkel cell carcinoma. Copyright © 1995, Wiley Blackwell. All rights reserved

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Primary cutaneous plasmacytosis: Report of three cases and review of the literature

H. Uhara, T. Saida, S. Ikegawa, Y. Yamazaki, H. Mikoshiba, S. Nijoh, K. Kitano, C. S. Koh

Dermatology   189 ( 3 ) 251 - 255  1994年  [査読有り]

　概要を見る

Background: Cutaneous plasmacytosis is a rare disease characterized by peculiar multiple eruptions and hypergammaglobulinemia. More than 40 cases have been reported, mainly in Japan, although information concerning the disorder was limited to individual case reports. Objective and Methods: To clarify the clinicopathological and laboratory features, we reviewed 41 cases. Results: All patients were Japanese and the male-to-female ratio was 1:0.6. The onset ages ranged from 20 to 62 years, with a mean and median of 37 and 37 years. A superficial lymphadenopathy was detected in 58% (22/38), and polyclonal hypergammaglobulinemia was found in 93% (38/41). No cases were associated with any apparent underlying diseases. The course was chronic without spontaneous remission. Four patients died, 3 of whom succumbed to leukemia, respiratory failure or renal failure, respectively. Conclusion: The results suggest that the condition appears to be a variant of reactive plasmacytic disorders of unknown origin. © 1994 S. Karger AG, Basel.

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