Details of a Researcher - Iwata, Takashi

Papers - Iwata, Takashi

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仲村, 勝, 藤井, 多久磨, 西尾, 浩, 岩田, 卓 and 青木, 大輔

産婦人科の実際 57 ( 11 ) 1734 - 1740 2008

ISSN 0558-4728

Epigenetic inactivation of the CHFR gene in cervical cancer contributes to sensitivity to taxanes

Banno, K., Yanokura, M., Kawaguchi, M., Kuwabara, Y., Akiyoshi, J., Kobayashi, Y., Iwata, T., Hirasawa, A., Fujii, T., Susumu, N., Tsukazaki, K. and Aoki, D.

Int J Oncol 31 ( 4 ) 713 - 20 2007.10

ISSN 1019-6439

A relationship between inactivation of mitotic checkpoint genes and sensitivity of cancer cells to anticancer agents has been reported. We investigated the effect of epigenetic inactivation by aberrant hypermethylation of the mitotic checkpoint gene CHFR (checkpoint with forkhead and ring finger) on the sensitivity of cervical cancer cells to taxanes. Methylation-specific PCR (MSP) of cervical smears showed aberrant methylation of CHFR in 12.3% (2/14) of adenocarcinoma specimens. In contrast, aberrant DNA methylation was not detected in normal cervical cells or squamous cell carcinoma cells. Aberrant methylation of CHFR was also analyzed in 6 human cervical carcinoma-derived cell lines and was observed in SKG-IIIb and HeLa cells. These cell lines showed high sensitivity to taxanes, but became taxane-resistant upon treatment with 5-azacytidine. Furthermore, suppression of CHFR expression in siRNA-transfected SKG-IIIa cells caused increased sensitivity to taxanes. In conclusion, aberrant methylation of the CHFR gene may be useful as a molecular marker for selection of therapy for patients with cervical adenocarcinoma with a poor prognosis, and may also suggest a new therapeutic strategy of targeting CHFR in cervical cancer. To our knowledge, this study is the first to examine epigenetic inactivation by aberrant hypermethylation of CHFR in cervical cancer.

Epigenetic inactivation of the CHFR gene in cervical cancer contributes to sensitivity to taxanes

Banno Kouji, Yanokura Megumi, Kawaguchi Makiko, Kuwabara Yoshiko, Akiyoshi Jyunko, Kobayashi Yusuke, Iwata Takashi, Hirasawa Akira, Fujii Takuma, Susumu Nobuyuki, Tsukazaki Kastumi, Aoki Daisuke

International Journal of Oncology 31 ( 4 ) 713 - 720 2007.10

ISSN 1019-6439

A relationship between inactivation of mitotic checkpoint genes and sensitivity of cancer cells to anticancer agents has been reported. We investigated the effect of epigenetic inactivation by aberrant hypermethylation of the mitotic checkpoint gene CHFR (checkpoint with forkhead and ring finger) on the sensitivity of cervical cancer cells to taxanes. Methylation-specific PCR (MSP) of cervical smears showed aberrant methylation of CHFR in 12.3% (2/14) of adenocarcinoma specimens. In contrast, aberrant DNA methylation was not detected in normal cervical cells or squamous cell carcinoma cells. Aberrant methylation of CHFR was also analyzed in 6 human cervical carcinoma-derived cell lines and was observed in SKG-IIIb and HeLa cells. These cell lines showed high sensitivity to taxanes, but became taxane-resistant upon treatment with 5-azacytidine. Furthermore, suppression of CHFR expression in siRNA-transfected SKG-IIIa cells caused increased sensitivity to taxanes. In conclusion, aberrant methylation of the CHFR gene may be useful as a molecular marker for selection of therapy for patients with cervical adenocarcinoma with a poor prognosis, and may also suggest a new therapeutic strategy of targeting CHFR in cervical cancer. To our knowledge, this study is the first to examine epigenetic inactivation by aberrant hypermethylation of CHFR in cervical cancer.

莢膜細胞腫に合併した子宮体癌の1例

青海, 咲子, 岩田, 卓, 飯塚, 真, 小川, 誠司, 味八木, 寿子, 山上, 聖子, 松本, 直, 上野, 和典, 片岡, 史夫, 山下, 博, 新井, 宏治 and 廣瀬, 茂道

日本産科婦人科学会東京地方部会会誌 2007

症例は71歳、3経妊2経産。不正出血を主訴に来院した。内診では子宮は正常大、両側付属器を触知せず、経腟超音波断層法で内膜肥厚を認めた。頸部細胞診、内膜細胞診ともにclass II、内膜組織診は単純型子宮内膜増殖症であった。6ヵ月後の再検でも同様の結果であったため、その時点での治療は必要ないと判断し、患者希望で他院での定期検査とした。2年後に再度不正出血があり紹介受診となった。受診時、内膜細胞診はclass II、内膜組織診は単純型子宮内膜増殖症であり、右付属器に充実性腫瘍を認めたため、臨床経過よりエストロゲン産生腫瘍に伴う子宮内膜増殖症の可能性を考え、単純子宮全摘術・両側付属器切除術を行った。術後病理組織診断は莢膜細胞腫および子宮体癌I a期であった。閉経後にエストロゲン高値および充実性卵巣腫瘍認める場合、エストロゲン産生腫瘍の可能性および子宮内膜癌の併発を念頭に置く必要がある。

【誤診しやすい腫瘍・類腫瘍】 Peritoneal inclusion cyst　嚢胞性卵巣腫瘍との鑑別

岩田, 卓, 山下, 博, 新井, 宏治 and 青木, 大輔

産科と婦人科 74 ( 6 ) 676 - 683 2007

ISSN 0386-9792

【女性と生活習慣病】がん

岩田, 卓, 新井, 宏治 and 青木, 大輔

HORMONE FRONTIER IN GYNECOLOGY 14 ( 1 ) 59 - 64 2007

ISSN 1340-220X

肥満者ではインスリンやIGF-1(insulin-like growth factor-1)などの細胞増殖因子の分泌が増加し、子宮内膜がんをはじめ乳がん、大腸がん、腎がんなどの発がん要因となる。中でも子宮内膜組織においては閉経前と閉経後で機序は異なるものの、エストロゲンによる増殖刺激が肥満により亢進するため、特にがん化の関連が強い。一方、乳がんについては閉経後肥満女性での発がんの危険率は増加するが、閉経前肥満女性では逆に低下するとされている。本稿では肥満者における子宮内膜がんと乳がんの発がん機序を中心に、婦人科がんを生活習慣病の視点から解説する。(著者抄録)

【婦人科悪性腫瘍の術前診断(がんの局在、局所的および遠隔転移)のピットホール】子宮頸部0期がん・初期がんの診断に円錐切除は有用か　有用なので比較的に適応範囲を広くしている

岩田, 卓, 藤井, 多久磨, 平尾, 薫丸 and 青木, 大輔

産婦人科の世界 59 ( 8 ) 679 - 684 2007

ISSN 0386-9873

右付属器切除術後に月経困難症が発症した単角孤立性副角子宮の1例

山上, 聖子, 林, 茂徳, 岩田, 卓, 青海, 咲子, 飯塚, 真, 小川, 誠司, 味八木, 寿子, 松本, 直, 上野, 和典, 片岡, 史夫, 山下, 博, 新井, 宏治 and 廣瀬, 茂道

日本産科婦人科学会東京地方部会会誌 56 ( 3 ) 315 - 318 2007

ISSN 0288-5751

右付属器切除術後に月経困難症が増悪し、双角子宮との鑑別が困難であった単角孤立性副角子宮の症例を経験したので報告する。症例は41歳女性、1経妊1経産。右下腹部痛を主訴に来院し、MRIにて右チョコレート嚢腫と双角子宮を認めた。右卵巣嚢腫に対して右付属器切除術を行い術後病理組織診断では、内膜症性嚢胞であった。術後月経困難症状の増悪を認めたため、MRIを再度撮影したところ、子宮右側に内膜症性嚢胞の再発を疑わせる腫瘤を認めた。内膜症の根治目的で単純子宮全摘出術、腫瘍摘出術、左付属器切除術を施行、術後病理組織検査により腫瘍は内膜症性病変ではなく、孤立性副角の診断となった。本患者の子宮は双角子宮ではなく孤立性副角子宮であり、右付属器切除術の際の卵管切除のために月経血の流出を妨げ、子宮留血腫を形成し症状の増悪を引き起こしたと考えられた。子宮奇形の症例では、術前診断をより適確にする必要があると考えられた。(著者抄録)

A novel cancer testis antigen that is frequently expressed in pancreatic, lung, and endometrial cancers

Okada Takaho, Akada Masanori, Fujita Tomonobu, Iwata Takashi, Goto Yasufumi, Kido Kenji, Okada Tsutomu, Matsuzaki Yuriko, Kobayashi Kouichi, Matsuno Seiki, Sunamura Makoto, Kawakami Yutaka

Clinical Cancer Research 12 ( 1 ) 191 - 197 2006.01

ISSN 1078-0432

Purpose: To isolate cancer testis antigens that are expressed in pancreatic cancers and may be useful in clinical applications. Experimental Design: To efficiently isolate cancer testis antigens, a testis cDNA library was immunoscreened (SEREX) with serum from a patient with pancreatic ductal adenocarcinoma. The expression of isolated antigens in various cancer cell lines and tissues was evaluated by reverse transcription-PCR and Northern blot analyses. The immunogenicity of the antigen in cancer patients was evaluated by detection of the IgG antibody in sera from patients with various cancers. Results: Of the three clones isolated through screening of a total of 2 × 10⁶ cDNA library clones, one clone (KU-CT-1) was found to be expressed in various cancers but only in testis among normal tissues, indicating that it was a novel cancer testis antigen. The KU-CT-1 gene is located on chromosome 10p12 and produces two splice variants, which encode proteins of 397 and 872 amino acids, respectively. KU-CT-1 was expressed in pancreatic cancer tissues (3 of 9, 33%), lung cancer tissues (9 of 24, 38%), and endometrial cancer tissues (7 of 11, 64%). Specific serum IgG antibodies were detected in 3 of 20 pancreatic cancer patients, 2 of 12 endometrial cancer patients, 1 of 18 colon cancer patients, and 1 of 10 prostate cancer patients but not detected in 30 healthy individuals. Conclusions: KU-CT-1 is a new cancer testis antigen that is expressed in pancreatic, lung, and endometrial cancers and may be useful for diagnosis and immunotherapy for patients with various cancers. © 2006 American Association for Cancer Research.

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A novel cancer testis antigen that is frequently expressed in pancreatic, lung, and endometrial cancers

Okada, T., Akada, M., Fujita, T., Iwata, T., Goto, Y., Kido, K., Matsuzaki, Y., Kobayashi, K., Matsuno, S., Sunamura, M. and Kawakami, Y.

Clin Cancer Res 12 ( 1 ) 191 - 7 2006.01

ISSN 1078-0432

To isolate cancer testis antigens that are expressed in pancreatic cancers and may be useful in clinical applications.|To efficiently isolate cancer testis antigens, a testis cDNA library was immunoscreened (SEREX) with serum from a patient with pancreatic ductal adenocarcinoma. The expression of isolated antigens in various cancer cell lines and tissues was evaluated by reverse transcription-PCR and Northern blot analyses. The immunogenicity of the antigen in cancer patients was evaluated by detection of the IgG antibody in sera from patients with various cancers.|Of the three clones isolated through screening of a total of 2 x 10(6) cDNA library clones, one clone (KU-CT-1) was found to be expressed in various cancers but only in testis among normal tissues, indicating that it was a novel cancer testis antigen. The KU-CT-1 gene is located on chromosome 10p12 and produces two splice variants, which encode proteins of 397 and 872 amino acids, respectively. KU-CT-1 was expressed in pancreatic cancer tissues (3 of 9, 33%), lung cancer tissues (9 of 24, 38%), and endometrial cancer tissues (7 of 11, 64%). Specific serum IgG antibodies were detected in 3 of 20 pancreatic cancer patients, 2 of 12 endometrial cancer patients, 1 of 18 colon cancer patients, and 1 of 10 prostate cancer patients but not detected in 30 healthy individuals.|KU-CT-1 is a new cancer testis antigen that is expressed in pancreatic, lung, and endometrial cancers and may be useful for diagnosis and immunotherapy for patients with various cancers.

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結節性硬化症に関連する子宮組織奇形　大量出血にて発症した1例

利安, 隆史, 水沼, 仁孝, 加藤, 弘毅, 菅原, 俊祐, 白石, 悟, 末盛, 友浩, 岩田, 卓 and 西川, 眞史

臨床放射線 51 ( 10 ) 1241 - 1245 2006

ISSN 0009-9252

31歳女。不正性器出血持続、大量性器出血で緊急入院となった。貧血に対し輸血が施行され、.経腟エコーで右卵巣腫瘍が疑われ、MRが施行された。骨盤内には子宮と一塊となった内部構造不均一な腫瘤病変を認めた。子宮後面には異常な腔があり、内部には出血信号を示す液体貯留が存在した。CTでは非常に血流に富み内部不均一な骨盤内腫瘤、大量の腹腔内出血、骨盤内右側には高濃度血腫を認めた。造影で腫瘍腹側は強く濃染され、腫瘍左側に造影剤の血管外漏出が疑われた。経皮的塞栓術施行のため血管造影を施行、骨盤血管造影を行うと右内腸骨動脈が欠損し、代わりに左内腸骨が代償性に拡張していた。左子宮動脈をジェルフォーム細片、ボルテックスコイル2本で塞栓した。

【婦人科がん治療周辺領域の進歩】細胞診断　子宮頸がん検診におけるHPV検査の有用性

岩田, 卓, 藤井, 多久磨, 平尾, 薫丸, 斎藤, 深雪, 仲村, 勝, 大野, 暁子, 石川, 光也, 塚崎, 克己 and 青木, 大輔

産婦人科の世界 58 ( 12 ) 1111 - 1118 2006

ISSN 0386-9873

最近、当院で経験した絨毛性疾患の2例

飯塚, 真, 岩田, 卓, 青海, 咲子, 小川, 誠司, 山上, 聖子, 味八木, 寿子, 松本, 直, 上野, 和典, 片岡, 史夫, 山下, 博 and 新井, 宏治

日本産科婦人科学会東京地方部会会誌 55 ( 4 ) 448 - 453 2006

ISSN 0288-5751

我々が経験した臨床的絨毛癌および臨床的侵入奇胎の症例を報告する。症例1は39歳0経妊0経産。胞状奇胎の掻爬術後、経過順調型であったが術後8ヵ月目に血中hCGβ値が再上昇した。子宮に病巣はなく、肺に病巣を認めたため絨毛癌診断スコアにより臨床的絨毛癌と診断し、さらにWHO予後スコアによって低リスク症例と判定した。当初、アクチノマイシンDの単剤投与を行ったが、治療期間中にhCGβ値が上昇したため、EMA療法に変更し寛解となった。しかし寛解後8ヵ月で血中hCGβ値の再上昇認め、EMA療法を再開して再度寛解となった時点で肺病巣切除と子宮全摘術を行った。症例2は34歳0経妊0経産。胞状奇胎の掻爬術後、4週目に血中hCGβ値が上昇した。子宮筋層に原発巣を認め、同時に肺転移巣と思われる腫瘤を認めた。絨毛癌診断スコアにより臨床的侵入奇胎と診断し、WHO予後スコアによって中等度リスク症例と判定した。MAC療法を行って寛解となった。絨毛性疾患の治療にあたってはその厳密な診断および治療の選択が重要であると考えられた。(著者抄録)

Immune responses to DNA mismatch repair enzymes hMSH2 and hPMS1 in patients with pancreatic cancer, dermatomyositis and polymyositis

Okada Takaho, Noji Shinobu, Goto Yasufumi, Iwata Takashi, Fujita Tomonobu, Okada Tsutomu, Matsuzaki Yuriko, Kuwana Masataka, Hirakata Michito, Horii Akira, Matsuno Seiki, Sunamura Makoto, Kawakami Yutaka

International Journal of Cancer 116 ( 6 ) 925 - 933 2005.10

ISSN 0020-7136

To identify tumor antigens useful for diagnosis and immunotherapy of patients with pancreatic ductal adenocarcinoma, we applied a SEREX approach with a cDNA library made from 5 pancreatic cancer cell lines and sera obtained from 8 patients with pancreatic cancer, and isolated total 32 genes, including 14 previously characterized genes and 18 genes with unknown functions. Among these isolated antigens, serum IgG antibodies for 2 isolated DNA mismatch repair enzymes, Homo sapiens mutS homolog 2 (HMSH2) and Homo sapiens postmeiotic segregation increased 1 (hPMS1), were detected in patients with pancreatic ductal adenocarcinoma and dermatomyositis (DM), and polymyositis (PM), but not in sera from healthy individuals. Immunohistochemical study demonstrated that hMSH2 and hPMS1 were over-expressed in pancreatic ductal adenocarcinoma compared to normal pancreatic ducts. These results suggested that hMSH2 and hPMS1 may be useful as CD4+ helper T cell antigens for immunotherapy of pancreatic cancer patients and that serum IgG antibodies may be useful for diagnosis of patients with pancreatic ductal adenocarcinoma and DM/PM. © 2005 Wiley-Liss, Inc.

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Immune responses to DNA mismatch repair enzymes hMSH2 and hPMS1 in patients with pancreatic cancer, dermatomyositis and polymyositis

Okada, T., Noji, S., Goto, Y., Iwata, T., Fujita, T., Matsuzaki, Y., Kuwana, M., Hirakata, M., Horii, A., Matsuno, S., Sunamura, M. and Kawakami, Y.

Int J Cancer 116 ( 6 ) 925 - 33 2005.10

ISSN 0020-7136

To identify tumor antigens useful for diagnosis and immunotherapy of patients with pancreatic ductal adenocarcinoma, we applied a SEREX approach with a cDNA library made from 5 pancreatic cancer cell lines and sera obtained from 8 patients with pancreatic cancer, and isolated total 32 genes, including 14 previously characterized genes and 18 genes with unknown functions. Among these isolated antigens, serum IgG antibodies for 2 isolated DNA mismatch repair enzymes, Homo sapiens mutS homolog 2 (hMSH2) and Homo sapiens postmeiotic segregation increased 1 (hPMS1), were detected in patients with pancreatic ductal adenocarcinoma and dermatomyositis (DM), and polymyositis (PM), but not in sera from healthy individuals. Immunohistochemical study demonstrated that hMSH2 and hPMS1 were over-expressed in pancreatic ductal adenocarcinoma compared to normal pancreatic ducts. These results suggested that hMSH2 and hPMS1 may be useful as CD4+ helper T cell antigens for immunotherapy of pancreatic cancer patients and that serum IgG antibodies may be useful for diagnosis of patients with pancreatic ductal adenocarcinoma and DM/PM.

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Frequent immune responses to a cancer/testis antigen, CAGE, in patients with microsatellite instability - Positive endometrial cancer

Iwata Takashi, Fujita Tomonobu, Hirao Nobumaru, Matsuzaki Yuriko, Okada Tsutomu, Mochimaru Hiroshi, Susumu Nobuyuki, Matsumoto Eri, Sugano Kokichi, Yamashita Naohide, Nozawa Shiro, Kawakami Yutaka

Clinical Cancer Research 11 ( 10 ) 3949 - 3957 2005.05

ISSN 1078-0432

Purpose: Identification of cancer/testis antigens useful for diagnosis or immunotherapy of cancers was attempted by cDNA expression cloning with patients' sera (SEREX). Experimental Design: cDNA expression libraries made from testis or endometrial cancer cell lines were screened using sera from patients with endometrial cancer or melanoma patients immunized with dendritic cells pulsed with autologous tumor lysates. Tissue-specific expression by RT-PCR and immunogenicity by Western blotting of the bacterial recombinant antigen with sera from cancer patients were evaluated. Results: A cancer/testis antigen, CAGE, was isolated by two independently performed SEREX. CAGE was expressed in various cancer cell lines including endometrial cancer, colon cancer, and melanoma in 7 of 10 endometrial cancer tissues and in 1 of 3 atypical endometrial hyperplasia, but not in normal tissues including the endometrium and testis. The protein expression on cancer cells was confirmed by Western blot analysis with the recombinant CAGE protein, anti-CAGE IgG antibody was detected in sera from 5 of 45 endometrial cancer, 2 of 24 melanoma, and 2 of 33 colon cancer patients, but not in sera from healthy individuals. By ELISA analysis, anti-CAGE antibody was detected in 12 of 45 endometrial cancer, 2 of 20 melanoma, and 4 of 33 colon cancer patients. Intriguingly, anti-CAGE antibody was highly positive in 7 of the 13 (53.8%) microsatellite instability (MSI)-H patients with endometrial cancer, but negative in 20 non-MSI-H patients (P = 0.001). Conclusion: CAGE may be useful for immunotherapy and diagnosis of various cancers particularly MSI-positive endometrial cancer. © 2005 American Association for Cancer Research.

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Frequent immune responses to a cancer/testis antigen, CAGE, in patients with microsatellite instability-positive endometrial cancer

Iwata, T., Fujita, T., Hirao, N., Matsuzaki, Y., Okada, T., Mochimaru, H., Susumu, N., Matsumoto, E., Sugano, K., Yamashita, N., Nozawa, S. and Kawakami, Y.

Clin Cancer Res 11 ( 10 ) 3949 - 57 2005.05

ISSN 1078-0432

Identification of cancer/testis antigens useful for diagnosis or immunotherapy of cancers was attempted by cDNA expression cloning with patients' sera (SEREX).|cDNA expression libraries made from testis or endometrial cancer cell lines were screened using sera from patients with endometrial cancer or melanoma patients immunized with dendritic cells pulsed with autologous tum or lysates. Tissue-specific expression by RT-PCR and immunogenicity by Western blotting of the bacterial recombinant antigen with sera from cancer patients were evaluated.|A cancer/testis antigen, CAGE, was isolated by two independently performed SEREX. CAGE was expressed in various cancer cell lines including endometrial cancer, colon cancer, and melanoma in 7 of 10 endometrial cancer tissues and in 1 of 3 atypical endometrial hyperplasia, but not in normal tissues including the endometrium and testis. The protein expression on cancer cells was confirmed by Western blot analysis with the recombinant CAGE protein, anti-CAGE IgG antibody was detected in sera from 5 of 45 endometrial cancer, 2 of 24 melanoma, and 2 of 33 colon cancer patients, but not in sera from healthy individuals. By ELISA analysis, anti-CAGE antibody was detected in 12 of 45 endometrial cancer, 2 of 20 melanoma, and 4 of 33 colon cancer patients. Intriguingly, anti-CAGE antibody was highly positive in 7 of the 13 (53.8%) microsatellite instability (MSI)-H patients with endometrial cancer, but negative in 20 non-MSI-H patients (P = 0.001).|CAGE may be useful for immunotherapy and diagnosis of various cancers particularly MSI-positive endometrial cancer.

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ICSI後の月経中にDICにいたった子宮腺筋症の一例

末盛, 友浩, 浅井, 哲, 加藤, 直子, 佐藤, 健二, 岩田, 卓 and 白石, 悟

栃木県産婦人科医報 32 ( 1 ) 33 - 35 2005

【研修医のための身体所見のとり方】　産婦人科的診察について

岩田, 卓, 久布白, 兼行 and 野澤, 志朗

診断と治療 93 ( 4 ) 523 - 528 2005

ISSN 0370-999X

子宮原発の脂肪肉腫類似腫瘍の一例

浅井, 哲, 櫻井, 友義, 末盛, 友浩, 加藤, 直子, 佐藤, 健二, 岩田, 卓, 郡山, 智, 白石, 悟 and 西川, 眞史

栃木県産婦人科医報 32 ( 1 ) 26 - 29 2005

症例は71歳,3経妊3経産,閉経50歳.他院にて子宮癌検診時に超音波断断層法で高輝度な子宮腫瘍を指摘され,当院を紹介受診した.特に自覚症状はなかった.骨盤MRIではT1およびT2強調画像にて高信号を呈していたが,一部低信号領域が混在する不整な像を認める腫瘍であった.また脂肪抑制像では信号が抑制されたことから脂肪性腫瘍であると推測した.以上より子宮平滑筋脂肪腫を考えたが,内部不均一な画像より鑑別診断として子宮肉腫も否定できず,腹式単純子宮全摘出術および両側付属器切除術を行った.摘出標本での腫瘍部は割面像が境界明瞭な黄色の結節で,一部に灰白色を呈し,特に肉眼的変性像は認めなかった.病理組織学的には脂肪成分が分化型脂肪肉腫に類似していたが,平滑筋成分には悪性と断定しうる所見は認められなかった.子宮原発の脂肪肉腫は極めて発生頻度が少なく,病理診断は非常に困難であったため,最終診断として「子宮原発の分化型脂肪肉腫類似の脂肪成分を有する平滑筋性腫瘍」との表現とした(著者抄録)

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