研究者詳細 - 中村　圭一郎

論文 - 中村　圭一郎

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Age-dependent Alteration in Mitochondrial Dynamics and Autophagy in Hippocampal Neuron of Cannabinoid CB1 Receptor-deficient Mice. 国際誌

Kosuke Kataoka, Andras Bilkei-Gorzo, Chihiro Nozaki, Akinobu Togo, Keiichiro Nakamura, Keisuke Ohta, Andreas Zimmer, Toru Asahi

Brain research bulletin 160 40 - 49 2020年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Endocannabinoid system activity contributes to the homeostatic defense against aging and thus may counteract the progression of brain aging. The cannabinoid type 1 (CB1) receptor activity declines with aging in the brain, which impairs neuronal network integrity and cognitive functions. However, the underlying mechanisms that link CB1 activity and memory decline remain unknown. Mitochondrial activity profoundly influences neuronal function, and age-dependent mitochondrial activity change is one of the known hallmarks of brain aging. As CB1 receptor is expressed on mitochondria and may regulate neuronal energy metabolism in hippocampus, we hypothesized that CB1 receptors might influence mitochondria in hippocampal neurons. Here, we found that CB1 receptor significantly affected mitochondrial autophagy (mitophagy) and morphology in an age-dependent manner. Serine 65-phosphorylated ubiquitin, a key marker for mitophagy, was reduced in adult CB1-deficient mice (CB1-KO) compared to those in wild type controls, particularly in CA1 pyramidal cell layer. Transmission electron microscopy (TEM) analysis showed reduced mitophagy-like events in hippocampus of adult CB1-KO. TEM analysis also showed that mitochondrial morphology in adult CB1-KO mice was altered shown by an increase in thin and elongated mitochondria in hippocampal neurons. 3D reconstruction of mitochondrial morphology after scanning electron microscopy additionally revealed an enhanced density of interconnected mitochondria. Altogether, these findings suggest that reduced CB1 signaling in CB1-KO mice leads to reduced mitophagy and abnormal mitochondrial morphology in hippocampal neurons during aging. These mitochondrial changes might be due to the impairments in mitochondrial quality control system, which links age-related decline in CB1 activity and impaired memory.

DOI： 10.1016/j.brainresbull.2020.03.014

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Seromucinous borderline tumorにおける術前検査所見の後方視的検討

清水かれん, 原賀順子, 松原侑子, 松岡敬典, 小川千加子, 中村圭一郎, 増山寿

現代産婦人科 68 ( 2 ) 239 - 244 2020年6月

記述言語：日本語出版者・発行元：中国四国産科婦人科学会

2014年6月に女性生殖器腫瘍のWHO分類第4版が刊行され、新たにseromucinous tumorという分類が加えられた。改訂後5年が経過し、しばしば症例を経験するが、術前診断は容易ではない。そこで、我々はseromucinous borderline tumor(SMBT)の術前診断における画像検査や血液検査の特徴を示すことを目的とし、検討を行った。方法は、2006年3月から2019年4月までに当院で手術を行い、病理組織診断でSMBT、もしくは2014年改定によりSMBTに包括されたmullerian mixed-epitherial borderline tumor、endocervical-like mucinous borderline tumorと診断された21例を対象とし、診療録を参照し後方視的に検討した。対象年齢の年齢は中央値49歳、病期はI期20例(95.2%)、III期1例(4.8%)であった。血清中CA125は中央値63.2U/mLであり、35U/mL以上の異常高値を示した例は13例(61.9%)であった。腫瘍径は中央値6.0cmであった。MRI所見では15例(71.4%)において嚢胞内容液はT1強調画像で高信号を示し、子宮内膜症の存在を反映していた。T2強調画像では充実部分の低信号のコアとその周囲の高信号がSMBTの特徴とされるが、その所見を認めたのは8例(38.1%)であった。造影効果については既存の報告と同様に、様々な造影強度であった。今回SMBT21例の画像所見を中心に検討を行ったが、一定の特徴はあるものの非典型例も多数認めた。術前診断の精度向上にはさらなる症例の蓄積が望まれる。(著者抄録)

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Risk of Gynecologic Cancer as Second versus First Primary Cancer in Japan

Chikako Ogawa, Keiichiro Nakamura, Hirofumi Matsuoka, Yuko Matsubara, Junko Haraga, Hisashi Masuyama

ACTA MEDICA OKAYAMA 74 ( 2 ) 109 - 114 2020年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

This study aimed to determine whether the risk conferred by gynecologic cancer (GC) as second primary cancer (SPC) differs from that associated with GC as first primary cancer (FPC). We investigated the correlations between FPC/SPC and the characteristics and prognoses of 1,645 GC patients (701 with cervical cancer [CC], 641 with endometrial cancer [EM], and 303 with ovarian cancer [OV]). The X-2 test and the Kaplan-Meier method were used to determine whether FPC/SPC and the characteristics and prognoses of GC patients. Of the SPC patients, 26 (3.7%) had CC, 53 (8.3%) had EM, and 31(10.2%) had OV. The most common previous cancer type in SPC of GC patients was breast cancer, which was observed in 13 patients (50.0%) with CC, 23 (43.4%) with EM, and 16 (51.6%) with OV. In all patients with CC, EM, and OV as SPC, the stage was significantly associated with recurrence. There were no significant differences in the morbidity or mortality of CC, EM, or OV patients between those with FPC and those with SPC. The risk of SPC development in GC patients varied, ranging from 3.5% (CC) to 10.3% (OV) of patients.

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The presence of chronic diseases contributes to the occurrence risk factors for gynecological cancers in Japan

Kazuhiro Okamoto, Keiichiro Nakamura, Hirofumi Matsuoka, Yuko Matsubara, Junko Haraga, Chikako Ogawa, Hisashi Masuyama

MOLECULAR AND CLINICAL ONCOLOGY 12 ( 4 ) 336 - 342 2020年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPANDIDOS PUBL LTD

The aim of the present study was to determine whether chronic diseases (CD), such as hypertension, diabetes mellitus, dyslipidemia, heart diseases and cerebrovascular diseases, are occurrence risk factors and affect the survival of patients with gynecological cancers (GC). The correlations between CD and the characteristics and survival of 1,590 GC patients [685 with cervical cancer (CC), 613 with endometrial cancer (EM) and 292 with ovarian cancer (OV)] were investigated in the present study. Of the CD patients, 189 had CC (27.6%), 265 had EM (43.2%) and 72 had OV (24.7%). The incidence of CD increased with age in GC patients. The number of CD patients aged >= 70 years, was 8.6-fold higher in the CC group, 3.0-fold higher in the EM group, and 9.6-fold higher in the OV group compared with those aged <50 years. CD and excess body weight were associated with GC regardless of patient age. However, there was no correlation between CD and survival at any age in GC patients. These findings indicate that CD contribute to >24% of the occurrence risk factors in GC patients in Japan.

DOI： 10.3892/mco.2020.1989

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The presence of chronic diseases contributes to the occurrence risk factors for gynecological cancers in Japan. 国際誌

Kazuhiro Okamoto, Keiichiro Nakamura, Hirofumi Matsuoka, Yuko Matsubara, Junko Haraga, Chikako Ogawa, Hisashi Masuyama

Molecular and clinical oncology 12 ( 4 ) 336 - 342 2020年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

The aim of the present study was to determine whether chronic diseases (CD), such as hypertension, diabetes mellitus, dyslipidemia, heart diseases and cerebrovascular diseases, are occurrence risk factors and affect the survival of patients with gynecological cancers (GC). The correlations between CD and the characteristics and survival of 1,590 GC patients [685 with cervical cancer (CC), 613 with endometrial cancer (EM) and 292 with ovarian cancer (OV)] were investigated in the present study. Of the CD patients, 189 had CC (27.6%), 265 had EM (43.2%) and 72 had OV (24.7%). The incidence of CD increased with age in GC patients. The number of CD patients aged ≥70 years, was 8.6-fold higher in the CC group, 3.0-fold higher in the EM group, and 9.6-fold higher in the OV group compared with those aged <50 years. CD and excess body weight were associated with GC regardless of patient age. However, there was no correlation between CD and survival at any age in GC patients. These findings indicate that CD contribute to >24% of the occurrence risk factors in GC patients in Japan.

DOI： 10.3892/mco.2020.1989

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Risk of Gynecologic Cancer as Second versus First Primary Cancer in Japan.

Chikako Ogawa, Keiichiro Nakamura, Hirofumi Matsuoka, Yuko Matsubara, Junko Haraga, Hisashi Masuyama

Acta medica Okayama 74 ( 2 ) 109 - 114 2020年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

This study aimed to determine whether the risk conferred by gynecologic cancer (GC) as second primary cancer (SPC) differs from that associated with GC as first primary cancer (FPC). We investigated the correlations between FPC/SPC and the characteristics and prognoses of 1,645 GC patients (701 with cervical cancer [CC], 641 with endometrial cancer [EM], and 303 with ovarian cancer [OV]). The χ2 test and the Kaplan-Meier method were used to determine whether FPC/SPC and the characteristics and prognoses of GC patients. Of the SPC patients, 26 (3.7%) had CC, 53 (8.3%) had EM, and 31 (10.2%) had OV. The most common previous cancer type in SPC of GC patients was breast cancer, which was observed in 13 patients (50.0%) with CC, 23 (43.4%) with EM, and 16 (51.6%) with OV. In all patients with CC, EM, and OV as SPC, the stage was significantly associated with recurrence. There were no significant differences in the morbidity or mortality of CC, EM, or OV patients between those with FPC and those with SPC. The risk of SPC development in GC patients varied, ranging from 3.5% (CC) to 10.3% (OV) of patients.

DOI： 10.18926/AMO/58268

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子宮頸癌治療後における筋肉量(骨格筋量・腸腰筋量)変化の検討

松岡敬典, 中村圭一郎, 松原侑子, 原賀順子, 小川千加子, 増山寿

日本産科婦人科学会雑誌 72 ( 臨増 ) S - 314 2020年3月

hCGの下降が非順調型であった肺転移を伴う侵入奇胎の1例

兼森雅敏, 久保光太郎, 松原侑子, 松岡敬典, 原賀順子, 小川千加子, 中村圭一郎, 増山寿

日本産科婦人科学会雑誌 72 ( 臨増 ) S - 452 2020年3月

【やさしくわかる産科婦人科検査マスターブック】(第2章)婦人科腫瘍分野がん化学療法のQOL評価

中村圭一郎, 原賀順子, 増山寿

産科と婦人科 87 ( Suppl. ) 195 - 199 2020年3月

Reduction in HPV16/18 prevalence among young women with high-grade cervical lesions following the Japanese HPV vaccination program. 国際誌

Koji Matsumoto, Nobuo Yaegashi, Takashi Iwata, Kasumi Yamamoto, Yoichi Aoki, Masao Okadome, Kimio Ushijima, Shoji Kamiura, Kazuhiro Takehara, Koji Horie, Nobutaka Tasaka, Kenzo Sonoda, Yuji Takei, Yoichi Aoki, Katsuyuki Konnai, Hidetaka Katabuchi, Keiichiro Nakamura, Mitsuya Ishikawa, Hidemichi Watari, Hiroyuki Yoshida, Noriomi Matsumura, Hidekatsu Nakai, Shogo Shigeta, Fumiaki Takahashi, Kiichiro Noda, Hiroyuki Yoshikawa

Cancer science 110 ( 12 ) 3811 - 3820 2019年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

The Japanese government began a human papillomavirus (HPV) vaccination program for girls aged 12-16 years in 2010 but withdrew its recommendation in 2013 because of potential adverse effects, leading to drastically reduced vaccination uptake. To evaluate population-level effects of HPV vaccination, women younger than 40 years of age newly diagnosed with cervical intraepithelial neoplasia grade 1-3 (CIN1-3), adenocarcinoma in situ (AIS), or invasive cervical cancer (ICC) have been registered at 21 participating institutes each year since 2012. A total of 7709 women were registered during 2012-2017, of which 5045 were HPV genotyped. Declining trends in prevalence of vaccine types HPV16 and HPV18 during a 6-year period were observed in CIN1 (50.0% to 0.0%, Ptrend < .0001) and CIN2-3/AIS (83.3% to 45.0%, Ptrend = .07) only among women younger than 25 years of age. Overall, HPV vaccination reduced the proportion of HPV16/18-attributable CIN2-3/AIS from 47.7% to 33.0% (P = .003): from 43.5% to 12.5% as routine vaccination (P = .08) and from 47.8% to 36.7% as catch-up vaccination (P = .04). The HPV16/18 prevalence in CIN2-3/AIS cases was significantly reduced among female individuals who received their first vaccination at age 20 years or younger (P = .02). We could not evaluate vaccination effects on ICC owing to low incidence of ICC among women aged less than 25 years. We found HPV vaccination to be effective in protecting against HPV16/18-positive CIN/AIS in Japan; however, our data did not support catch-up vaccination for women older than 20 years. Older adolescents who skipped routine vaccination due to the government's suspension of its vaccine recommendation could benefit from receiving catch-up vaccination before age 20 years.

DOI： 10.1111/cas.14212

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Histologic Appearance and Immunohistochemistry of DNA Mismatch Repair Protein and p53 in Endometrial Carcinosarcoma Impact on Prognosis and Insights Into Tumorigenesis

Masayuki Saijo, Keiichiro Nakamura, Naoyuki Ida, Atsuko Nasu, Tadashi Yoshino, Hisashi Masuyama, Hiroyuki Yanai

AMERICAN JOURNAL OF SURGICAL PATHOLOGY 43 ( 11 ) 1493 - 1500 2019年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

Endometrial carcinosarcoma (ECS) is a rare and aggressive mixed-type epithelial and mesenchymal tumor. This study focused on the histologic appearance, loss of DNA mismatch repair (MMR) protein expression, and aberrant p53 expression in the epithelial component, and overall prognosis of 57 cases with ECS. Histologically, 21 and 36 cases exhibited low-grade (endometrioid grade 1 and 2) and high-grade (others) epithelial components, respectively. In a Kaplan-Meier analysis, patients with a high-grade epithelial component exhibited worse progression-free survival (PFS), compared with those with a low-grade component. Although the former group also exhibited worse overall survival, the difference was not significant. Thirty-six cases exhibited aberrant p53 expression. Of these, 5 cases exhibited focally aberrant p53 expression in carcinomatous components with diffuse aberrant p53 expression in mesenchymal components. Aberrant expression of p53 did not show significant association with prognosis. Six patients with MMR deficiency exhibited relatively better PFS. In conclusion, a low-grade epithelial component is a superior predictor of the PFS of ECS, compared with MMR protein and p53 expression status. In some cases of ECS, TP53 mutation may be a late event associated with histogenesis of the sarcomatous component.

DOI： 10.1097/PAS.0000000000001353

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Histologic Appearance and Immunohistochemistry of DNA Mismatch Repair Protein and p53 in Endometrial Carcinosarcoma: Impact on Prognosis and Insights Into Tumorigenesis. 国際誌

Masayuki Saijo, Keiichiro Nakamura, Naoyuki Ida, Atsuko Nasu, Tadashi Yoshino, Hisashi Masuyama, Hiroyuki Yanai

The American journal of surgical pathology 43 ( 11 ) 1493 - 1500 2019年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1097/PAS.0000000000001353

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Pre-treatment psoas major volume is a predictor of poor prognosis for patients with epithelial ovarian cancer. 国際誌

Yuko Matsubara, Keiichiro Nakamura, Hirofumi Matsuoka, Chikako Ogawa, Hisashi Masuyama

Molecular and clinical oncology 11 ( 4 ) 376 - 382 2019年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Low skeletal muscle mass (sarcopenia) is an important prognostic risk factor for the outcome of a variety of cancer types. The current study investigated whether skeletal muscle area (SMA), psoas area (PA) and psoas major volume (PV) are associated with progression-free survival (PFS) and overall survival (OS) in patients with epithelial ovarian cancer (OC). A total of 92 OC patients were enrolled in the present study. Pre-treatment with SMA and PA was assessed using computed tomography (CT) and PV was calculated using a three-dimensional-CT (3D-CT). The clinical factors associated with sarcopenia and prognosis were retrospectively evaluated. For all patients, the median PFS and OS were 19 and 32 months, respectively. Patients exhibiting lower PV (<195.6 cm3) had significantly poorer PFS and OS compared with patients exhibiting higher PV (≥195.6 cm3; P=0.018 and P=0.006), while those with low SMA (<92.92 cm2) had significantly worse OS than patients with higher SMA (≥92.92 cm2; P=0.030). PV was also demonstrated to be superior to SMA and PA in prognosis prediction. PV by 3D-CT can serve as an indicator of poor prognosis in patients with OC.

DOI： 10.3892/mco.2019.1912

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前置癒着胎盤のCesarean hysterectomyに総腸骨動脈バルーン閉塞術(CIABO)を併用し総腸骨動脈解離を発症した一例

築澤良亮, 衛藤英理子, 牧尉太, 玉田祥子, 光井崇, 早田桂, 中村圭一郎, 増山寿

現代産婦人科 68 ( Suppl. ) S46 - S46 2019年9月

Assessment of glucose kinetics with real-time continuous glucose monitoring during labor. 国際誌

Jota Maki, Eriko Eto, Shoko Tamada, Takashi Mitsui, Kei Hayata, Keiichiro Nakamura, Yuji Hiramatsu, Hisashi Masuyama

The journal of obstetrics and gynaecology research 45 ( 9 ) 1851 - 1859 2019年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: Changes in glucose levels during labor have not been sufficiently investigated in pregnant women. Using real-time continuous glucose monitoring, we aimed to assess glucose kinetics during labor among pregnant women with gestational diabetes mellitus (PwGDM), and those with normal glucose tolerance (PwNGT). METHODS: Japanese PwGDM and PwNGT who had planned a transvaginal delivery at Okayama University Hospital were enrolled. The correlation between changes in glucose levels during labor among the PwGDM and PwNGT groups at four time periods was assessed: (i) active phase of 1st stage of labor; (ii) 2nd stage of labor; (iii) postpartum 0-12 h; and (iv) postpartum 12-48 h. RESULTS: In total, 18 and 22 PwGDM and PwNGT, respectively, were enrolled. During labor, both groups had similar changes in glucose levels over time, which peaked during period 3. The main effect of glucose level changes was the labor period (P < 0.001), not the presence of gestational diabetes mellitus. Furthermore, differences in glucose levels in the PwGDM group were observed between periods 1 and 2 (P = 0.037), 1 and 3 (P = 0.024), 3 and 4 (P = 0.005); differences in glucose levels in the PwNGT group were observed between periods 3 and 4 (P = 0.024). CONCLUSION: During labor, both PwGDM and PwNGT groups showed similar changes in glucose levels over time. During delivery, the PwGDM who regularly measured their own glucose levels could be managed using the same nutritional management methods as those for PwNGT.

DOI： 10.1111/jog.14058

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Seromucinous borderline tumorにおける術前検査所見の後方視的検討

清水かれん, 原賀順子, 松原侑子, 松岡敬典, 小川千加子, 中村圭一郎, 増山寿

現代産婦人科 68 ( Suppl. ) S60 - S60 2019年9月

Predictors for pathological parametrial invasion in clinical stage IIB cervical cancer. 国際誌

Koji Matsuo, Muneaki Shimada, Keiichiro Nakamura, Yuji Takei, Kimio Ushijima, Toshiyuki Sumi, Tatsuru Ohara, Hideaki Yahata, Mikio Mikami, Toru Sugiyama

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 45 ( 8 ) 1417 - 1424 2019年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: To examine predictors of pathological parametrial invasion in clinical stage IIB cervical cancer, and to examine prognostic factors in pathological stage IIB disease. METHODS: This study is an ancillary analysis of a nation-wide retrospective cohort examining 6,003 clinical stage IB-IIB cervical cancers. Women with clinical stage IIB disease who underwent primary radical hysterectomy with lymphadenectomy were examined (n = 714). Multivariate analysis was performed to identify independent clinico-pathological factors for pathological parametrial invasion and to identify independent prognostic factors in pathological stage IIB disease. RESULTS: Parametrial invasion was identified on the surgical specimen in 400 cases (56.0%, 95% confidence interval 52.4-59.7). On multivariate analysis, deep stromal invasion (DSI, adjusted-OR 3.922), multiple pelvic nodal metastases (adjusted-OR 3.266), lympho-vascular space invasion (adjusted-OR 2.333), and uterine corpus invasion (adjusted-OR 1.656) remained independent tumor factors for pathological parametrial invasion. In classification-tree models, tumors with DSI and multiple pelvic nodal metastases had the highest incidence of pathological parametrial invasion (75.0-87.7%); contrary, tumors without DSI had the lowest incidence (21.9%). Among patients with pathological stage IIB disease, the absolute difference in 5-year disease-free survival rates was 57.2%, ranging between 80.9% in those with squamous histology with none/single pelvic nodal metastasis and 23.7% in those with non-squamous histology with multiple pelvic nodal metastases. CONCLUSION: In clinical stage IIB cervical cancer, accuracy for pathological parametrial invasion is low-modest. With absence of DSI, only one in five clinical stage IIB diseases has pathological stage IIB disease. Survival of pathological stage IIB varies widely and is largely dependent on nodal factors.

DOI： 10.1016/j.ejso.2019.02.019

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ロボット支援下子宮悪性腫瘍手術における助手の重要性

久保光太郎, 松原侑子, 松岡敬典, 原賀順子, 小川千加子, 鎌田泰彦, 中村圭一郎, 増山寿

日本産科婦人科内視鏡学会雑誌 35 ( Suppl.I ) 123 - 123 2019年8月

後腹膜に発生した巨大Lipoleiomyomaの一例

片山沙希, 久保光太郎, 松岡敬典, 依田尚之, 西田傑, 小川千加子, 中村圭一郎, 増山寿

現代産婦人科 67 ( 2 ) 341 - 345 2019年6月

記述言語：日本語出版者・発行元：中国四国産科婦人科学会

Lipoleiomyomaは稀な良性腫瘍であり、その多くは子宮体部発生であり後腹膜発生は稀である。今回我々は、術中に後腹膜由来と判明したLipoleiomyomaの1例を経験したので文献的考察を交えて報告する。症例は58歳女性、1ヵ月前より急速に進行する腹部膨満感を主訴に前医を受診した。MRI検査にて、腹腔内を占める30cm超の巨大腫瘤を指摘された。卵巣癌が疑われ、当院を紹介受診された。当院で画像を再読影し、画像所見から子宮筋腫変性が第一に疑われたが発生由来臓器は特定できなかった。治療と診断目的にて開腹手術の方針となった。腫瘍は柔らかく後腹膜腔に存在しており、子宮との連続性は認められなかった。腫瘍は内容液を含め10kgを超えていた。子宮と両側付属器は肉眼的に異常所見を認めなかったが、腫瘍が子宮由来である可能性も考慮し、子宮全摘出術と両側付属器切除を施行した。術中出血は1250mlと多く、輸血を必要とした。術後病理検査ではLipoleiomyomaであり、術後経過は良好であった。Lipoleiomyomaは閉経前後の女性に多く認められ、急速増大した症例報告も認められている。後腹膜発生の症例も報告されているが、画像診断のみでは発生由来の判別は困難な場合もある。脂肪組織を含有する巨大な骨盤内腫瘍を認めた場合には当疾患も念頭において、十分な準備の後に手術を選択する必要がある。(著者抄録)

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当院で縮小手術を施行した75歳以上の子宮体癌患者の検討

依田尚之, 中村圭一郎, 松原侑子, 西條昌之, 松岡敬典, 西田傑, 小川千加子, 増山寿

日本婦人科腫瘍学会雑誌 37 ( 3 ) 503 - 503 2019年6月

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