今日の臨床サポート

下腹部腫瘤

著者: 池田智明1) 三重大学 病態解明医学講座生殖病態生理学

著者: 島田京子2) 倉敷成人病センター 産婦人科

監修: 小林裕明 鹿児島大学大学院医歯学総合研究科生殖病態生理学

著者校正/監修レビュー済:2019/02/07

概要・推奨   

所見のポイント:
  1. 下腹部腫瘤感やそれによる圧迫症状は、産婦人科外来にて比較的頻度が高く見られる主訴である。
  1. 急に下半身が太ったと感じたり、下腹部が出ている気がするなどの場合には、下腹部腫瘤の評価が必要になる。下腹部に触るとしこりや塊にふれることもある。
 
診断へのアプローチ:(アルゴリズム:)
  1. 産婦人科領域の下腹部腫瘤で重要性の高いものは、卵巣腫瘍と子宮腫瘍である。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
池田智明 : 特に申告事項無し[2021年]
島田京子 : 未申告[2021年]
監修:小林裕明 : 講演料(中外製薬株式会社,アストラゼネカ株式会社),奨学(奨励)寄付など(中外製薬株式会社)[2021年]

改訂のポイント:
  1. 産婦人科診療ガイドライン 婦人科外来編2017
に基づき一部修正を行った。

病態・疫学・診察

疫学情報・病態・注意事項  
  1. 産婦人科領域の下腹部腫瘤で重要性の高いものは、卵巣腫瘍と子宮腫瘍である。また卵巣腫瘍には発生年齢による背景と組織学的特徴があり、診断するうえで参考になる[1]<図表>
  1. 思春期女子の場合は、重複子宮や片側腟管閉鎖などによる月経血貯留と貯留部位の腫大に代表されるMüller管形成障害も考慮する。
  1. 産婦人科領域外では、消化管から発生する消化管間質腫瘍(gastrointestinal stromal tumor、GIST)との鑑別が必要となる。
  1. 卵巣子宮内膜症は、卵巣ホルモンの影響により腫大・進行するが、約1%に悪性腫瘍(卵巣癌)が発生するので注意が必要である。また卵巣癌は同年齢のすべての悪性腫瘍の約3%とされている。
  1. なお下腹部腫瘤で頻度の高い疾患は卵巣腫瘍と子宮筋腫であるが、本稿では卵巣腫瘍、特に卵巣悪性腫瘍を中心に概説し、 子宮筋腫 の詳細は別項に譲る。また鑑別診断として類似した臨床症状を呈する場合があるGISTにも言及したい。

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文献 

著者: John O Schorge, Susan C Modesitt, Robert L Coleman, David E Cohn, Noah D Kauff, Linda R Duska, Thomas J Herzog
雑誌名: Gynecol Oncol. 2010 Oct;119(1):7-17. doi: 10.1016/j.ygyno.2010.06.003. Epub 2010 Aug 7.
Abstract/Text Ovarian cancer is a heterogeneous, rapidly progressive, highly lethal disease of low prevalence. The etiology remains poorly understood. Numerous risk factors have been identified, the most prominent involving an inherited predisposition in 10% of cases. Women with germline mutations associated with Hereditary Breast/Ovarian Cancer and Lynch syndromes have dramatically elevated risks (up to 46% and 12%, respectively). Risk-reducing salpingo-oophorectomy is the best method to prevent ovarian cancer in these high-risk women. Significant risk reduction is also seen in the general population who use oral contraceptives. Since up to 89% patients with early-stage disease have symptoms prior to diagnosis, increased awareness of the medical community may facilitate further workup in patients who otherwise would have had a delay. Despite enormous effort, there is no proof that routine screening for ovarian cancer in either the high-risk or general populations with serum markers, sonograms, or pelvic examinations decreases mortality. Further evaluation is needed to determine whether any novel biomarkers, or panels of markers, have clinical utility in early detection. Prospective clinical trials have to be designed and completed prior to offering of any of these new diagnostic tests. CA125 is currently the only biomarker recommended for monitoring of therapy as well as detection of recurrence. This commentary provides an overview on the background, screening and surveillance of ovarian cancer.

Copyright © 2010 Elsevier Inc. All rights reserved.
PMID 20692025  Gynecol Oncol. 2010 Oct;119(1):7-17. doi: 10.1016/j.ygy・・・
著者: David M Purdie, Christopher J Bain, Victor Siskind, Penelope M Webb, Adèle C Green
雑誌名: Int J Cancer. 2003 Mar 20;104(2):228-32. doi: 10.1002/ijc.10927.
Abstract/Text Incessant ovulation is thought to be one of the primary causes of epithelial ovarian cancer. However, the effects of ovulation at different ages and of the various exposures or events that suppress ovulation have not been established. We used data from an Australian case-control study of 791 ovarian cancer cases and 853 controls to examine the effect of ovulation on ovarian cancer risk. The total number of lifetime ovulations was calculated using information provided in a monthly contraceptive/reproductive calendar, as well as incorporating other information such as average menstrual cycle length. An increase of 1 year's worth of ovulation was associated with a 6% increase in risk of ovarian cancer (95% confidence interval [CI] = 4-8%). Ovulations in the 20-29-year age group were associated with the greatest risk, with a 20% increase in risk associated with each year of ovulation during this age period (95% CI = 13-26%). When the effects of different exposures that suppress ovulation were compared, there was an indication that some factors may have a greater effect than others. These findings support the theory that incessant ovulation is a major contributor to the occurrence of ovarian cancer and suggest that ovulations during the 20s may be those most associated with disease risk.

Copyright 2003 Wiley-Liss, Inc.
PMID 12569579  Int J Cancer. 2003 Mar 20;104(2):228-32. doi: 10.1002/i・・・
著者: Tomas Riman, Paul W Dickman, Staffan Nilsson, Nestor Correia, Hans Nordlinder, Cecilia M Magnusson, Ingemar R Persson
雑誌名: Am J Epidemiol. 2002 Aug 15;156(4):363-73.
Abstract/Text This case-control study evaluated reproductive and other factors in relation to epithelial ovarian cancer (EOC) risk. Between 1993 and 1995, the authors recruited 655 EOC cases and 3,899 population controls aged 50-74 years who were born in and residents of Sweden. Data were collected through mailed questionnaires. Odds ratios were estimated by unconditional logistic regression. Parity reduced EOC risk (odds ratio = 0.61, 95% confidence interval (CI): 0.46, 0.81) for uniparous compared with nulliparous women. The risk of EOC decreased with incomplete pregnancies, early menopausal age, late age at first birth, and unilateral oophorectomy; increased with family history of ovarian cancer; and was not associated with menarcheal age, lactation, irregular menses, and menopausal symptoms. Histology-specific odds ratios of EOC for ever compared with never users of oral contraceptives were: serous, 0.56 (95% CI: 0.42, 0.74); mucinous, 1.96 (95% CI: 1.04, 3.68); endometrioid, 0.71 (95% CI: 0.49, 1.03); clear cell, 0.66 (95% CI: 0.31, 1.43); and all EOCs, 0.73 (95% CI: 0.59, 0.90). Prolonged oral contraceptive use reduced EOC risk, with persistent protection up to 25 years after the last use. Ever use of hormone replacement therapy increased EOC risk (odds ratio = 1.41, 95% CI: 1.15, 1.72). Among etiologic hypotheses, the retrograde transportation hypothesis accommodates most epidemiologic findings concerning EOC risk.

PMID 12181107  Am J Epidemiol. 2002 Aug 15;156(4):363-73.
著者: S E Hankinson, D J Hunter, G A Colditz, W C Willett, M J Stampfer, B Rosner, C H Hennekens, F E Speizer
雑誌名: JAMA. 1993 Dec 15;270(23):2813-8.
Abstract/Text OBJECTIVE: To assess whether tubal ligation and hysterectomy affect subsequent risk of ovarian cancer.
DESIGN: Prospective cohort study with 12 years of follow-up.
SETTING: United States, multistate.
PARTICIPANTS: A total of 121,700 female registered nurses who were 30 to 55 years of age in 1976; the follow-up rate was 90% as of 1988.
MAIN OUTCOME MEASURE: Ovarian cancer of epithelial origin confirmed by medical record review.
RESULTS: We observed a strong inverse association between tubal ligation and ovarian cancer, which persisted after adjustment for age, oral contraceptive use, parity, and other ovarian cancer risk factors (multivariate relative risk [RR], 0.33; 95% confidence interval [CI], 0.16 to 0.64). The association was similar when we assessed tubal ligation status at the baseline questionnaire and excluded cases in the first 4 years to eliminate any possible short-term decrease in risk due to screening of the ovaries during ligation surgery. We noted a weaker inverse association between simple hysterectomy and ovarian cancer (RR, 0.67; 95% CI, 0.45 to 1.00). Neither vasectomy nor condom use by a partner was associated with risk of ovarian cancer.
CONCLUSIONS: These data indicate that tubal ligation, and perhaps hysterectomy, may substantially reduce risk of epithelial ovarian cancer.

PMID 8133619  JAMA. 1993 Dec 15;270(23):2813-8.
著者: American College of Obstetricians and Gynecologists, ACOG Committee on Practice Bulletins--Gynecology, ACOG Committee on Genetics, Society of Gynecologic Oncologists
雑誌名: Obstet Gynecol. 2009 Apr;113(4):957-66. doi: 10.1097/AOG.0b013e3181a106d4.
Abstract/Text Hereditary breast and ovarian cancer syndrome is an inherited cancer-susceptibility syndrome. The hallmarks of this syndrome are multiple family members with breast cancer or ovarian cancer or both, the presence of both breast cancer and ovarian cancer in a single individual, and early age of breast cancer onset. Clinical genetic testing for gene mutations allows physicians to more precisely identify women who are at substantial risk of breast cancer and ovarian cancer. For these individuals, screening and prevention strategies can be instituted to reduce their risks. Obstetricians and gynecologists play an important role in the identification and management of women with hereditary breast and ovarian cancer syndrome.

PMID 19305347  Obstet Gynecol. 2009 Apr;113(4):957-66. doi: 10.1097/AO・・・
著者: Irene Visintin, Ziding Feng, Gary Longton, David C Ward, Ayesha B Alvero, Yinglei Lai, Jeannette Tenthorey, Aliza Leiser, Ruben Flores-Saaib, Herbert Yu, Masoud Azori, Thomas Rutherford, Peter E Schwartz, Gil Mor
雑誌名: Clin Cancer Res. 2008 Feb 15;14(4):1065-72. doi: 10.1158/1078-0432.CCR-07-1569. Epub 2008 Feb 7.
Abstract/Text PURPOSE: Early detection would significantly decrease the mortality rate of ovarian cancer. In this study, we characterize and validate the combination of six serum biomarkers that discriminate between disease-free and ovarian cancer patients with high efficiency.
EXPERIMENTAL DESIGN: We analyzed 362 healthy controls and 156 newly diagnosed ovarian cancer patients. Concentrations of leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, and CA-125 were determined using a multiplex, bead-based, immunoassay system. All six markers were evaluated in a training set (181 samples from the control group and 113 samples from OC patients) and a test set (181 sample control group and 43 ovarian cancer).
RESULTS: Multiplex and ELISA exhibited the same pattern of expression for all the biomarkers. None of the biomarkers by themselves were good enough to differentiate healthy versus cancer cells. However, the combination of the six markers provided a better differentiation than CA-125. Four models with <2% classification error in training sets all had significant improvement (sensitivity 84%-98% at specificity 95%) over CA-125 (sensitivity 72% at specificity 95%) in the test set. The chosen model correctly classified 221 out of 224 specimens in the test set, with a classification accuracy of 98.7%.
CONCLUSIONS: We describe the first blood biomarker test with a sensitivity of 95.3% and a specificity of 99.4% for the detection of ovarian cancer. Six markers provided a significant improvement over CA-125 alone for ovarian cancer detection. Validation was performed with a blinded cohort. This novel multiplex platform has the potential for efficient screening in patients who are at high risk for ovarian cancer.

PMID 18258665  Clin Cancer Res. 2008 Feb 15;14(4):1065-72. doi: 10.115・・・
著者: Noah D Kauff, Susan M Domchek, Tara M Friebel, Mark E Robson, Johanna Lee, Judy E Garber, Claudine Isaacs, D Gareth Evans, Henry Lynch, Rosalind A Eeles, Susan L Neuhausen, Mary B Daly, Ellen Matloff, Joanne L Blum, Paul Sabbatini, Richard R Barakat, Clifford Hudis, Larry Norton, Kenneth Offit, Timothy R Rebbeck
雑誌名: J Clin Oncol. 2008 Mar 10;26(8):1331-7. doi: 10.1200/JCO.2007.13.9626. Epub 2008 Feb 11.
Abstract/Text PURPOSE: Risk-reducing salpingo-oophorectomy (RRSO) has been widely adopted as a key component of breast and gynecologic cancer risk-reduction for women with BRCA1 and BRCA2 mutations. Despite 17% to 39% of all BRCA mutation carriers having a mutation in BRCA2, no prospective study to date has evaluated the efficacy of RRSO for the prevention of breast and BRCA-associated gynecologic (ovarian, fallopian tube or primary peritoneal) cancer when BRCA2 mutation carriers are analyzed separately from BRCA1 mutation carriers.
PATIENTS AND METHODS: A total of 1,079 women 30 years of age and older with ovaries in situ and a deleterious BRCA1 or BRCA2 mutation were enrolled onto prospective follow-up studies at one of 11 centers from November 1, 1994 to December 1, 2004. Women self-selected RRSO or observation. Follow-up information through November 30, 2005, was collected by questionnaire and medical record review. The effect of RRSO on time to diagnosis of breast or BRCA-associated gynecologic cancer was analyzed using a Cox proportional-hazards model.
RESULTS: During 3-year follow-up, RRSO was associated with an 85% reduction in BRCA1-associated gynecologic cancer risk (hazard ratio [HR] = 0.15; 95% CI, 0.04 to 0.56) and a 72% reduction in BRCA2-associated breast cancer risk (HR = 0.28; 95% CI, 0.08 to 0.92). While protection against BRCA1-associated breast cancer (HR = 0.61; 95% CI, 0.30 to 1.22) and BRCA2-associated gynecologic cancer (HR = 0.00; 95% CI, not estimable) was suggested, neither effect reached statistical significance.
CONCLUSION: The protection conferred by RRSO against breast and gynecologic cancers may differ between carriers of BRCA1 and BRCA2 mutations. Further studies evaluating the efficacy of risk-reduction strategies in BRCA mutation carriers should stratify by the specific gene mutated.

PMID 18268356  J Clin Oncol. 2008 Mar 10;26(8):1331-7. doi: 10.1200/JC・・・
著者: Hiroshi Ishikawa, Scott Reierstad, Masashi Demura, Alfred W Rademaker, Tadayuki Kasai, Masaki Inoue, Hirokazu Usui, Makio Shozu, Serdar E Bulun
雑誌名: J Clin Endocrinol Metab. 2009 May;94(5):1752-6. doi: 10.1210/jc.2008-2327. Epub 2009 Feb 24.
Abstract/Text CONTEXT: Symptomatic uterine leiomyoma is associated with irregular uterine bleeding, anemia, and recurrent pregnancy loss. African-American women develop uterine leiomyomas at an earlier age and with higher frequency compared with Caucasian-American women or other races; however, the underlying mechanism for this discrepancy is unknown.
OBJECTIVE: Our objective was to determine whether gene targets of emerging leiomyoma therapeutics such as aromatase inhibitors and antiprogestins, which reduce tumor size and symptoms, are differentially expressed in tissues of African-American (n = 31), Caucasian-American (n = 34), and Japanese women (n = 36).
RESULTS: We found strikingly higher aromatase mRNA levels in leiomyoma compared with adjacent myometrium in African-American (83 fold), Caucasian-American (38 fold), and Japanese women (33 fold). Among the four major promoters that regulate aromatase expression in leiomyoma, the proximal promoter II accounted for higher aromatase mRNA levels in tissues from African-American women. Estrogen receptor subtype alpha mRNA levels were significantly, and 1.8- to 2.6-fold, higher in leiomyoma compared with adjacent myometrium in all groups, whereas leiomyoma estrogen receptor subtype beta mRNA levels were significantly elevated only in Japanese women. Leiomyoma progesterone receptor mRNA levels were significantly higher in Japanese women compared with African-American or Caucasian-American women.
CONCLUSIONS: Leiomyoma tissues from African-American women contained the highest level of aromatase expression, which may result in elevated tissue concentrations of estrogen, and account for the higher prevalence and earlier incidence. Analysis of leiomyoma tissue for biomarkers may predict the response to hormonal treatments such as aromatase inhibitors.

PMID 19240151  J Clin Endocrinol Metab. 2009 May;94(5):1752-6. doi: 10・・・
著者: Jennelle C Hodge, Cynthia C Morton
雑誌名: Hum Mol Genet. 2007 Apr 15;16 Spec No 1:R7-13. doi: 10.1093/hmg/ddm043.
Abstract/Text Uterine leiomyomata (UL), also known as fibroids, are the most common pelvic tumors in women of reproductive age and are the primary indication for hysterectomy in the USA. Many lines of evidence indicate a strong genetic component to the development of these tumors. In fact, approximately 40% of UL have non-random, tumor-specific chromosome abnormalities which have allowed classification into well-defined subgroups (deletion of portions of 7q, trisomy 12 or rearrangements of 12q15, 6p21 or 10q22) as well as identification of candidate genes for UL predisposition. Although benign, UL have been linked to malignancy through two genomic regions on chromosome 1. Mutation of fumarate hydratase (FH) at 1q43 is known to cause the Mendelian syndromes of multiple cutaneous and uterine leiomyomata (MCL) and hereditary leiomyomatosis and renal cell cancer (HLRCC), and recently, FH mutations have been detected in some non-syndromic UL. In addition, transcriptional profiling suggests that loss of the short arm of chromosome 1 in cellular leiomyomata, an uncommon histological variant of UL, may account in part for the presumed yet rare malignant transformation of UL to uterine leiomyosarcoma.

PMID 17613550  Hum Mol Genet. 2007 Apr 15;16 Spec No 1:R7-13. doi: 10.・・・

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