{"paper_id":"a43f9f60-85e2-40db-99c1-9e07ff047682","body_text":"DIAGNOSIS AND MANAGEMENT OF ADNEXAL MASS (H KA TABUCHI, SECTION EDITOR)\nClinical Management of Ovarian Endometriotic Cyst\n(Chocolate Cyst): Diagnosis, Medical Treatment, and\nMinimally Invasive Surgery\nMasaki Mandai & Ayako Suzuki & Noriomi Matsumura &\nTsukasa Baba & Ken Y amaguchi& Junzo Hamanishi &\nYumiko Y oshioka& Kenzo Kosaka & Ikuo Konishi\nPublished online: 7 January 2012\n# Springer Science+Business Media, LLC 2012\nAbstract In the clinical management of endometriotic cyst,\nthree major clinical disruptions need to be addressed ade-\nquately: pain, infertility, and malignant transformation. Symp-\ntoms differ according to the patient ’s age and her life stage,\nand they should be managed individually. This review dis-\ncusses the role of medical treatment with currently available\ndrug regimens as well as surgical interventions for endometri-\notic cyst in terms of each symptom. Endometriosis-associated\novarian cancer is an important issue in the management of\nendometriosis in relatively elderly women, although it is not\nyet widely recognized. The need for standard management of\nthese patients is also discussed.\nKeywords Endometriotic cyst . Chocolate cyst . Ovarian\ncyst . Pain . Infertility . ART. Endometriosis . Management .\nDiagnosis . Ultrasound . MRI . Medical treatment .\nLaparoscopy . Minimally invasive surgery . Ovarian cancer .\nEstrogen replacement\nIntroduction\nEndometriosis, defined as the presence of endometrium-like\ntissue outside the uterus, affects approximately 10% of women\nof reproductive age [1, 2]. The origin of ectopic endometrium\nremains unresolved: some gynecologists believe that it originates\nfrom endometrial tissue in the backflow of menstrual bleeding,\nwhereas others believe that it is a result of coelomic metaplasia\n[1]. These discrepancies yield continuous debates among gyne-\ncologists. Endometriosis affects many organs and structures,\nincluding the ovary, fallopian tube, pelvic serosa, rectum, retro-\nperitoneal structures (e.g., the ureter), and more remote organs,\nincluding the lungs. The most frequently affected organ is the\novary. Ovarian endometriosis typically presents as an ovarian\ncyst containing old blood; usually called achocolate cystor an\nendometriotic cyst, these are diagnosed in about 17% to 44% of\nwomen with endometriosis [2].\nAlthough the diagnosis of endometriosis is sometimes dif-\nficult, especially during early-stage disease, the characteristic\nappearance of a typical ovarian endometriotic cyst can be\neasily detected with MRI. After a diagnosis of ovarian endo-\nmetriotic cyst, there are several management options, including\ncareful follow-up, medication, and surgical intervention. The\nefficacy of these options is different according to the purpose\nof the treatment; for instance, medication is more effective for\nrelieving pain than for recovering fertility.\nEndometriosis causes three major clinical disruptions: pain,\ninfertility, and malignant transformation. The most common\nsymptom in younger patients is endometriosis-associated pain\nincluding dysmenorrhea, which, if mistreated, may lead to\nendometriosis-associated infertility. Endometriosis-associated\novarian cancer has been recognized recently. It generally\naffects elderly women, especially postmenopausal women\nwho are symptom-free and have no childbearing plans. Be-\ncause the symptoms and problems in patients with endometri-\nosis vary according to the woman ’s age, the severity of the\ndisease, and individual social requirements, the aim of treat-\nment should be specific to each patient (Fig.1). In this review,\nwe summarize the updated management of endometriotic cyst\nin several clinical situations.\nM. Mandai ( *) : A. Suzuki : N. Matsumura : T. Baba :\nK. Y amaguchi: J. Hamanishi : Y . Y oshioka: K. Kosaka :\nI. Konishi\nDepartment of Gynecology and Obstetrics,\nKyoto University Graduate School of Medicine,\n54 Shogoin Kawahara-cho, Sakyo-ku,\nKyoto 606-8507, Japan\ne-mail: mandai@kuhp.kyoto-u.ac.jp\nCurr Obstet Gynecol Rep (2012) 1:16 –24\nDOI 10.1007/s13669-011-0002-3\n\nDiagnosis of Endometriotic Cyst\nThe most useful diagnostic imaging modalities for endo-\nmetriotic cyst are ultrasonography (US) and MRI.\nExploratory Examination\nAlthough plentiful information can be obtained from imag-\ning analyses, the importanc e of a physical examination,\nespecially an internal examination, should not be over-\nlooked. With the aid of transvaginal US, careful internal\nexamination by the experienced physician can identify the\nsite causing pelvic pain and estimate the presence or absence\nof adhesions. Posttherapeutic improvement in pelvic tender-\nness detected by examination is as informative as improve-\nment detected by imaging analysis.\nUltrasonography\nUS is used mainly in outpatient clinics for the screening of\nan adnexal mass, following exploratory examination. Typi-\ncally, an ovarian endometriotic cyst presents with a diffuse,\nlow-echoic appearance with occasional hyperechoic foci in\nthe wall of unilocular or multilocular cysts 3 to 6 cm in\ndiameter [ 3, 4] (Fig. 2).\nDifferential diagnosis includes a mature cystic teratoma\n(or so-called dermoid cyst), which generally shows a more\nechogenic internal structure with an acoustic shadow reflect-\ning hairballs and calcifications. Other differential diagnoses\ninclude functional cysts, such as a lutein cyst or a hemor-\nrhagic follicular cyst, a tubo-ovarian abscess, and ovarian\ncancer [ 3]. Usually, differentiating an endometriotic cyst\nfrom other ovarian cysts is not difficult, using a precise\nevaluation of structural features and careful short-term\nfollow-up. However, it is occasionally difficult to exclude\nother possibilities, especially when the cyst contains a solid\nportion or shows a wall irregularity. This finding most often\nrepresents a hemorrhagic clot, but it is difficult to exclude\nmalignancy (Fig. 3). Color Doppler US may be useful for\nthe differential diagnosis, but its effectiveness remains un-\ncertain [ 5]. In such cases, further examination with MRI\nshould be considered [ 3].\nBecause it is neither invasive nor expensive, US is also\nuseful in the follow-up of endometriotic cyst. Regular\ncheck-ups every 6 months should be recommended. If any\nalteration in the US appearance is noticed, a closer follow-up\nor additional MRI examination is necessary.\nMagnetic Resonance Imaging\nMRI is one of the most powerful and informative diagnostic\ntools for an endometriotic cyst. Typically, an endometriotic\ncyst shows high intensity in both T1-weighted and T2-\nweighted images, reflecting the blood element in the cyst [ 3,\n6] (Fig. 2). A “shading” or “shading sign ” refers to a T2\nshortening in the cyst, corresponding to a hyperintense portion\non the T1 image, which is useful to distinguish endometriotic\ncyst from other blood-containing lesions, such as a hemor-\nrhagic corpus luteum cyst [ 3, 4]. Although the hypointensity\ntypically presents either as a focal/diffuse area or a layering\nwith a hypointense fluid level, a significant proportion of\ncases show only a complete loss of signal intensity [ 7]. Lack\nof fat suppression helps to distinguish an endometriotic cyst\nfrom a dermoid cyst [4]. In cases of endometriotic cyst with a\nInfertility\nPain\n(Menopause) Elder ageYounger age Reproductive age\nMedical care\nCurative (radical) treatmentPreservation of ovarian function\nMalignant transformation\nSurgical intervention\nFig. 1 The symptoms and problems in patients with endometriosis vary according to the age of the patient, the severity of the disease, and\nindividual social requirements. Therefore, the aim of treatment should be specific to each patient\nCurr Obstet Gynecol Rep (2012) 1:16 –24 17\n\nsolid portion, contrast enhancement is mandatory to exclude\nmalignancy, such as a clear cell carcinoma [ 3, 8].\nMalignant transformation of endometriotic cyst is the most\nserious problem related to late-stage endometriosis. If US\nscreening shows atypical findings such as a nodular portion,\nwall thickening, or a significant change in appearance during\nfollow-up, MRI is helpful not only to rule out malignancies\nbut also to estimate the histologic subtype of malignancies\n(Fig. 3). For this purpose, various parameters should be taken\ninto account, such as maximum diameter, the presence of\nshading, and the size and the nature of the nodular portion.\nThe most apparent risk factor is enhancement of the nodular\nportion, although a benign endometriotic cyst occasionally\nharbors an enhanced nodule. According to a study by Tanaka\net al. [ 9], the diameter of the cyst nodule is significantly\ncorrelated with a malignant phenotype. Lack of shading is\nalso an important finding in the malignant transformation of\nendometriosis, especially when MRI scans are repeated in the\nsame patient. Tanaka et al. [ 9] reported that 81% of benign\nendometriotic cysts showed shading on T2-weighted images,\nbut only 33% of malignant tumors showed shading. It is most\nlikely that a nonhemorrhagic secretion by malignant cells may\ndilute the cyst’s contents, causing the loss of shading. One of\nthe difficulties in diagnosing malignancy in endometriosis is a\ndecidualized endometriosis during pregnancy, which presents\nas a rapidly growing nodular portion or wall thickening with\nabundant vascularity in the endometriotic cyst. This finding\ncan be easily misdiagnosed as a malignancy [ 10–12]. In such\ncases, expectant management with careful serial follow-up is\nneeded. MRI is also useful to estimate histologic subtypes of\ncancer arising in endometriosis. In cases of endometrioid\ncancer, MRI shows either a solid or cystic pattern without\nshading [ 13]. The nodular portions in the cyst tend to be\nmultiple rather than single. In contrast, a clear cell carcinoma\ntends to be more cystic and unilocular, with one or several\nnodular portions [8].\nOne of the important roles of MRI in treating a patient\nwith an endometriotic cyst is the diagnosis of coexisting\nextraovarian endometriosis, as it has similar symptoms, such\nas pain and infertility. Diagnosing it is also helpful to ensure\nadequate surgical intervention. Endometriotic lesions fre-\nquently involve the surface of the peritoneum and ovary.\nFat-suppressed images are useful to identify the lesion, but a\ndiagnosis is relatively difficult, resulting in poor diagnostic\naccuracy [ 5]. The characteristic MRI pattern of superficial\nendometriosis is either high T1 intensity with low T2 inten-\nsity or high intensity in both T1 and T2 imaging. Deep\nendometriosis, sometimes referred to as posterior endome-\ntriosis, often affects retroperitoneal organs, including the\nureter and rectum. It frequently causes severe pelvic pain\nas a result of the involvement of the uterosacral ligament.\nThe sensitivity of diagnosis of deep endometriosis by MRI\nis reported to be 76% to 86% [ 3]. Adhesions caused by\nendometriosis are also important as a cause of infertility and\nfrequently make operation difficult. Using MRI, adhesions\nare typically identified by low-signal-intensity strands.\nFig. 2 Typical images of an endometriotic cyst.a Ultrasonography (US), showing a unilocular cyst with a diffuse and low-level echo within it.b–d On\nMRI scans, the contents of the cyst show high intensity in both T1-weighted and T2-weighted images, reflecting the blood element\n18 Curr Obstet Gynecol Rep (2012) 1:16 –24\n\nManagement of Endometriotic Cyst According\nto the Symptoms\nThe treatment options for ovarian endometriotic cyst are\neither medical or surgical interventions. Observation is an-\nother choice in some situations. Medical therapy typically\nconsists of androgens, progestogens, oral contraceptives\n(OCs), and gonadotropin-releasing hormone (GnRH) ago-\nnists. Surgical treatment for ovarian endometriotic cyst\nvaries from hysterectomy with salpingo-oophorectomy\n(SO) to unilateral cystectomy with or without laparoscopy.\nTreatment recommendations differ according to the purpose\nof treatment and the symptoms of the patient.\nTreatment of Endometriosis-Associated Pain\nAlthough ovarian endometriotic cyst could be a cause of\npelvic pain, it is rare that endometriotic cyst is the only\ncause of severe, chronic pain. Rather, accompanying extra-\novarian endometriosis or resulting adhesions or inflamma-\ntion may be responsible [ 14]. V arious drugs have been used\nto treat endometriosis-associated pain. A GnRH agonist is\nthe most popular treatment choice, and a number of placebo-\ncontrolled randomized studies have shown that these are\neffective [ 15]. Other drugs, such as danazol, OCs, and\ngestrinone have also been shown to be effective, with little\ndifference from GnRH agonists [ 15, 16, 17]. Dienogest, a\nselective progestin, was also as effective as GnRH agonists\n[18]. There are few published data, however, that indicate\nwhether medical treatment e ffectively alleviates pain in\nwomen with symptomatic endometriotic cyst. Rana et al.\nreported that a GnRH agonist or danazol is effective in\nreducing the size of an endometriotic cyst and in controlling\npelvic pain and dysmenorrhea [ 19].\nSurgery is thought to be the first line of treatment for pain\nin women with endometriotic cyst [15]. Surgical treatment to\nconserve bilateral ovaries includes drainage, sclerotherapy,\ndiathermy, laser vaporization, and cystectomy [20–22]. Drain-\nage guided by laparoscopy or transvaginal US has reportedly\nresulted in a high recurrence rate and is less effective for\nrelieving symptoms [ 20]. In addition, it can cause pelvic\ninfection or adhesions [ 20, 22]. Combining sclerotherapy\nusing ethanol, tetracycline, and methotrexate with aspiration\nmay reduce the rate of recurrence, although it can cause severe\nadhesions, which may affect future fertility [ 22, 23]. Ovarian\ncystectomy is a more definite treatment for endometriotic cyst.\nAlthough several studies found no difference among various\nsurgical procedures, including drainage, ablation, and cystec-\ntomy, randomized trials indicated a lower cumulative postop-\nerative rate of recurrence of dysmenorrhea, dyspareunia, and\nFig. 3 Images of a case of clear cell carcinoma, which arose in the\nsame patient as Fig. 2 after an interval of 6 years. a ultrasonography\n(US), showing that the cyst contains a solid portion and the cyst is\nlarger than it was 6 years ago. b–e On MRI scans, the cyst is unilocular\nand shows high intensity both in T2-weighted images ( b, c) and T1-\nweighted images ( d, e) with several nodular portions. These nodular\nportions show isointensity to high intensity in the T2-weighted image\nand low intensity in the T1-weighted images. e These portions also\nshow positive contrast enhancement (CE)\nCurr Obstet Gynecol Rep (2012) 1:16 –24 19\n\nchronic pelvic pain in patients who underwent cystectomy\ncompared with those who underwent drainage alone [ 21,\n22]. Another obvious advantage of cystectomy is that histo-\nlogic examination is available. Uterine nerve ablation (UNA)\nwas reported to be effective in relieving pain in earlier studies\n[22], but in recent randomized controlled trials, its effective-\nness in alleviating symptoms has been controversial. Several\nreports found no difference in symptoms at 3 years after\nsurgery between the women who underwent laparoscopy\nalone and the women who und erwent laparoscopy with\nUNA [24, 25]. Several authors reported modest clinical bene-\nfits of UNA [ 26, 27]. By contrast, many studies, including\nrandomized trials, showed that presacral neurectomy (PSN)\nsignificantly improved symptoms [25, 27, 28], although some\npatients suffered adverse effects from the procedure, including\nconstipation, bladder dysfunction, or intraoperative hemor-\nrhage. Radical treatment options for women who do not\nrequire fertility include oophorectomy and hysterectomy with\noophorectomy.\nThere are conflicting data on the role of postoperative\nmedical treatment. Randomized studies in which a GnRH\nagonist or danazol was used postoperatively for 3 months\ndid not show a difference in the recurrence of pain compared\nwith a nontreated group [29, 30]. In contrast, treatment with a\nGnRH agonist, danazol, or medroxyprogesterone acetate\n(MPA) for 6 months after operation showed a significant\nadvantage against the recurrence of pain in randomized con-\ntrolled trials [ 31, 32]. These data suggest that postoperative\nmedical treatment should be administered for at least 6 months\nand that treatment over a shorter period may not be beneficial\n[22].\nTreatment of Endometriosis-Associated Infertility\nBecause endometriosis is primarily a disease encountered in\nwomen of reproductive age, infertility is one of its most im-\nportant complications. The causal link between endometriosis\nand infertility is not clearly defined [ 33]. It is generally be-\nlieved that endometriosis impairs fertility in multiple ways [33,\n34]. First, severe pelvic pain may interfere with regular sexual\nintercourse in couples who are trying to conceive. Second,\nendometriosis destroys the pelvic anatomy as it progresses,\nthereby disrupting the normal fertilization procedure. The most\ndirect cause of infertility associated with endometriosis is tubal\nobstruction. Closure of the cul-de-sac, adhesions, and disloca-\ntion of the ovary or fallopian tube also interfere with natural\nconception. Third, in addition to these mechanical impair-\nments, endometriosis affects fertility chemically and biologi-\ncally. Inflammation caused by endometriosis alters the pelvic\nenvironment, with increases in inflammatory cytokines,\ngrowth factors, and angiogenic factors, which significantly\ndisrupt fertility [34]. For example, interleukins directly affect\nsperm motility, and tumor necrosis factor (TNF)- α causes\nDNA damage to the sperm [35–37]. These factors, along with\nreactive oxygen species (ROS) produced by endometriosis,\nalso impede sperm capacitation, oocyte-sperm interaction,\nand oocyte quality [33, 34].\nWhether the presence of ovarian endometriotic cyst affects\nthe normal ovarian function in terms of conception is unclear.\nIt is suggested that endometriosis does not affect the quality of\noocytes retained in the ovary. Rather, surgical intervention in\nthe endometriotic cyst may damage ovarian function to some\nextent. In this view, which surgical procedure is favorable for\nreproductive ability is a matter of concern [ 38].\nTreatment for endometriosis-associated infertility consists\nof\nmedical and surgical approaches, just as for pain. However,\nbecause the purpose of treatment is different, the treatment\nstrategy differs. The type of treatment may also be different for\npatients desiring natural conception and for those undergoing\nassisted reproductive technology (ART). Almost all medical\ntreatments for endometriosis are based on the hormonal block-\nage of ovarian function and are thus contraceptive; therefore,\nmedical treatment is usually not the chosen treatment for\nwomen pursuing spontaneous conception [ 34]. Evidence\nsuggests that there is no improvement in pregnancy rates with\nmedical intervention for endometriosis [39].\nAlthough removal of an ovarian endometriotic cyst is con-\nsidered to be effective in correcting disrupted pelvic anatomy, it\nis still undetermined whether surgical intervention for endome-\ntriosis, especially endometriotic cyst, contributes to natural\nconception [ 34]. The presence of endometriotic cyst may\naffect spontaneous ovulation [40]. Surgery for various degrees\nof endometriosis appears to improve the rate of natural con-\nception, but determining the optimal operative procedure for\nendometriotic cyst is another issue. Several reports, including\nrandomized controlled trials, indicate that ovarian cystectomy\nby way of laparoscopy is superior to drainage or vaporization in\nterms of higher pregnancy rates and lower recurrence rates [21,\n41]. Yazbeck et al. [ 23] suggested that ethanol sclerotherapy\nmay offer a better result because it causes less damage to the\nremaining ovarian function.\nFor patients who plan to undergo in vitro fertilization (IVF)\nafter treatment for infertility associated with endometriosis, the\nmanagement policy is different. It is estimated that 10–25% of\npatients undergoing IVF have accompanying endometriosis,\nand 17 –44% of them have endometriotic cyst [38 , 41]. The\npresence of endometriosis and its severity may negatively\nimpact the outcomes of IVF, though the relationship is not\ndefinitively proven [42]. Medical treatment for endometriotic\ncyst prior to IVF reduces the size of the cyst, and several\nrandomized controlled trials indicate that GnRH agonist treat-\nment before IVF in women with endometriosis significantly\nincreases pregnancy rates [43, 44].\nAs regards surgical intervention, Tsoumpou et al. [ 41]\nperformed a meta-analysis of five studies comparing surgical\ntreatment versus no treatment for ovarian endometriotic cyst.\n20 Curr Obstet Gynecol Rep (2012) 1:16 –24\n\nThe results showed no significant effect of treatment on IVF\npregnancy rates and on ovarian response to stimulation, com-\npared with no treatment. Nevertheless, the author mentioned\nthat the decision regarding surgery for endometriotic cyst in\nasymptomatic women before IVF should take into account the\nanticipated difficulty in accessing the follicles and the risk of\npelvic infection if inadvertent drainage of a large endometri-\notic cyst occurs at the time of retrieval. Expectant manage-\nment of endometriotic cyst before IVF presents risks that\ninclude difficulty in monitoring follicular growth and sponta-\nneous rupture and leakage, which may cause pelvic inflam-\nmation, infection, and adhesion. On the other hand, surgery\nmay cause quantitative damage to ovarian reserves, as a\ndecrease in the number of eggs has been observed after\novarian cystectomies, although the fertilization rates and the\nquality of the embryos did not differ [ 22].\nManagement of Endometriosis in Terms of Development\nof Ovarian Cancer\nIt is clinically evident that endometriosis gives rise to ovarian\ncancer with a relatively high frequency, and it has been shown\nthat women with endometriosis have a higher risk of ovarian\ncancer. According to a survey in Japan, approximately 1% of\ncases of ovarian endometriosis transform into ovarian cancer\n[45]. Importantly, this rate significantly increases in elderly\nwomen. The risk of ovarian cancer in patients with endome-\ntriosis is reported to be significantly higher than in the general\npopulation (standardized incidence ratio [SIR], 1.4–1.9), and\nthis risk increases in women with a longer history of endome-\ntriosis (SIR, 2.2–4.3) [46]. It is also well known that ovarian\ncancers arising from endometriosis have a unique histology:\nmost are of a clear cell or endometrioid subtype, relatively rare\nfor ovarian cancer [47].\nNumerous pathologic and molecular biologic data suggest\nthat endometriotic epithelium is actually a precursor of ovar-\nian cancer [ 47]. Continuation from morphologically benign\nendometriosis to cancer is frequently observed, and occasion-\nally an intermediate lesion, such as atypical endometriosis, is\nfound nearby [48]. The analysis of the loss of heterozygosity\n(LOH) and genetic mutations also indicates that endometriosis\nshares common genetic events with associated ovarian cancer\n[49]. These findings clearly show that ovarian cancer indeed\ndevelops from endometriosis, and that both conditions have\ncommon molecular pathways in their development. However,\nthe precise mechanism involved in the development of cancer\nin endometriosis is still unclear. V arious genetic events are\nimplicated, as is the effect of the microenvironment, such as\nendometriotic fluid containing highly concentrated iron [ 50,\n51].\nConsidering these facts, it is important to take the risk of\ncancer into account in managing endometriosis, especially in\nelderly women. There are few guidelines, however, on how to\nmanage endometriosis as a precursor of ovarian cancer. This\nlack is partly because the risk factors for ovarian cancer among\nwomen with endometriosis are not fully defined. Especially in\nthe case of endometrioid adenocarcinoma, and possibly in\nsome cases of clear cell and mixed-type carcinomas, estrogen\nplays an important role not only in the growth and maintenance\nof endometriosis, a precursor lesion of these cancers, but also\nin the development of cancer [ 47]. Mechanisms that may be\nimplicated in these conditions include unopposed estrogen\nstatus, increased expression of estrogenα, progesterone resis-\ntance, and increased aromatase activity, but these should be\nfurther elucidated [46]. In terms of clinical relevance, several\nauthors reported that estrogen replacement therapy (ERT) in-\ncreased the risk of ovarian cancer, especially of the endome-\ntrioid subtype [52]. Although it has not been directly shown\nthat estrogen increases the risk of endometriosis-associated\ncancer, this possibility should be considered when introducing\nERT in women who have a history of endometriosis, even after\nmenopause [ 52]. There are several reports of endometrioid\nadenocarcinoma in patients who underwent a hysterectomy\nwith bilateral oophorectomy for endometriosis with subse-\nquent long-term estrogen use [ 53]. It is generally recommen-\nded to add a progestin if ERT is necessary after menopause or\nafter a hysterectomy with oophorectomy for endometriosis\n[54].\nWhether surgical intervention is indicated for cancer pre-\nvention in women with endometriosis is an important issue but\nis not clearly defined. It is unclear whether conservative sur-\ngery, such as ovarian cystectomy or vaporization, reduces the\nr\nisk of malignant transformation of endometriosis [ 47]. As\npreviously mentioned, several surveys indicate that women\nwho have a longstanding history of endometriosis have a\ngreater risk of developing ovarian cancer [46], which suggests\nthat surgical intervention somehow may reduce the risk of\nmalignant transformation. Interestingly, women who under-\nwent a hysterectomy after a diagnosis of endometriosis did\nnot show an increased risk of ovarian cancer, thus indicating\nthat hysterectomy and possibly tubal ligation may have some\nprotective role [46]. For elderly women in whom endometri-\notic cyst has been diagnosed, early detection of cancer is\nclinically important. It is generally accepted that an endometri-\notic cyst growing after menopause should be resected.\nKobayashi et al. [ 55] demonstrated that the risk factors for\nmalignant transformation of endometriotic cyst are older age,\npostmenopausal status, and larger tumor size. They recom-\nmended considering surgery in postmenopausal women with\nan endometriotic cyst measuring 9 cm or larger.\nIt is still unclear whether medical treatment for endometri-\nosis reduces the risk of developing ovarian cancer. Oral contra-\nceptives are known to reduce ovarian cancer risk partly by\ninhibiting ovulation, which is thought to be a major risk for\novarian cancer. Together with their therapeutic effect on endo-\nmetriosis, OCs may reduce the risk of malignant transformation\nCurr Obstet Gynecol Rep (2012) 1:16 –24 21\n\nof endometriosis, but there is not yet any conclusive study on\nthis issue. The use of a GnRH agonist may reduce or increase\nthe risk of endometriosis-associated ovarian cancer because\nalthough postmenopausal status increases the risk of ovarian\ncancer, GnRH agonists suppress e ndometriosis itself. Newer\ndrugs such as dienogest may be used more frequently for\nendometriosis, but no data are yet available on their effect on\ncancer prevention. Clinical studies are needed on the effect of\nmedical care in preventing the development of endometriosis-\nassociated cancer.\nMinimally Invasive Surgery for Endometriotic Cyst\nAs mentioned above, various surgical procedures are used to\nmanage various symptoms derived from endometriosis. Re-\ncently, minimally invasive surgery under laparoscopy is becom-\ning the standard modality for the treatment of endometriosis,\nespecially in conservative therapy.\nLaparotomy V ersus Laparoscopy for Endometriosis\nWhether laparotomy or laparoscopic surgery is superior as a\nsurgical management technique for endometriosis is an im-\nportant issue. A number of reports, including controlled\ntrials, indicate that pregnancy rates, monthly fecundity, and\nrecurrence rates are comparable between laparotomy and\nlaparoscopy [ 56, 57]. On the other hand, blood loss, length\nof hospitalization, and recovery time are usually decreased\nafter laparoscopy [ 57]. It is generally thought that laparos-\ncopy is technically difficult and has a greater risk of surgical\ncomplications than laparotomy, but a meta-analysis of pro-\nspective randomized trials showed that laparoscopy and\nlaparotomy exposed patients equally to complications [ 58].\nTherefore, except in cases with special indications, laparo-\nscopic surgery is the first choice among surgical procedures\nfor infertile woman with endometriotic cyst.\nLaparotomy may be more applicable for women with\nsevere pelvic endometriosis if curative surgery is planned.\nHowever, even in very radical operations, such as REHCR\n(radical en bloc hysterectomy and colorectal resection), lapa-\nroscopy is reported to be comparable or superior to laparoto-\nmy in terms of symptoms and improvement in quality of life\n[59].\nExcision V ersus Ablative Surgery for Ovarian\nEndometriosis\nAs previously mentioned, surgical procedures, including lap-\naroscopic procedures, include salpingo-oophorectomy (with\nor without hysterectomy), ovarian cystectomy, ablation, and\ndrainage. Randomized trials clearly show that laparoscopic\nexcision of the cyst wall of an endometriotic cyst is superior to\nablation in terms of reduced recurrence, relief of pain, and\npregnancy rates [ 60]. Damage caused by the removal of\nnormal ovarian tissue in an excisional procedure is usually\nminimal, but Donnez et al. [ 61] have recommended using\nlaser vaporization for the portion close to the hilus.\nSurgery for Recurrent Endometriotic Cyst\nV ercellini et al. [62] reviewed the reports on the efficacy of\nrepeat surgery for recurrent endometriosis. Among 313 patients\nwho wanted to conceive after repeat surgery, 81 women be-\ncame pregnant, with no significant difference between laparot-\nomy and laparoscopy. However, the pregnancy rate after repeat\nsurgery was significantly lower than the rate after primary\nsurgery.\nConclusions\nThe roles of medical treatment with currently available\ndrug regimens and of surgical interventions for treating\nendometriosis-associated pain and infertility in women with\nendometriotic cyst have been intensively investigated and are\nby and large clear. In contrast, the effect of medication and\nsurgery on the development of cancer in women with endo-\nmetriosis is poorly understood, and no standard management\nfor endometriosis in terms of reducing malignant transforma-\ntion has been proposed. High-quality clinical trials are needed\nto help in establishing a standard care for endometriotic cyst,\nespecially after menopause.\nDisclosure No potential conflicts of interest relevant to this article\nwere reported.\nReferences\nRecently published papers of interest have been highlighted\nas\n Of importance\n1. Bulun SE. Endometriosis. 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Conservative surgical management of\nendometriosis in women with pelvic pain. J Minim Invasive Gyne-\ncol. 2006;13(6):546 –58.\n23. Y azbeck C, Madelenat P , Ayel JP , Jacquesson L, Bontoux LM,\nSolal P , Hazout A. Ethanol sclerotherapy: a treatment option for\novarian endometriomas before ovarian stimulation. Reprod\nBiomed Online. 2009;19(1):121 –5.\n24. V ercellini P , Aimi G, Busacca M, Apolone G, Uglietti A, Crosignani\nPG. Laparoscopic uterosacral ligament resection for dysmenorrhea\nassociated with endometriosis: results of a randomized, controlled\ntrial. Fertil Steril. 2003;80(2):310–9.\n25. Y eung Jr PP , Shwayder J, Pasic RP . Laparoscopic management of\nendometriosis: comprehensive review of best evidence. J Minim\nInvasive\nGynecol. 2009;16(3):269 –81.\n26. Johnson NP , Farquhar CM, Crossley S, Y u Y , V an Peperstraten\nAM, Sprecher M, Suckling J. A double-blind randomised con-\ntrolled trial of laparoscopic uterine nerve ablation for women with\nchronic pelvic pain. BJOG. 2004;111(9):950– 9.\n27. Latthe PM, Proctor ML, Farquhar CM, Johnson N, Khan KS.\nSurgical interruption of pelvic nerve pathways in dysmenorrhea:\na systematic review of effectiveness. Acta Obstet Gynecol Scand.\n2007;86(1):4–15.\n28. Tjaden B, Schlaff WD, Kimball A, Rock JA. The efficacy of\npresacral neurectomy for the relief of midline dysmenorrhea.\nObstet Gynecol. 1990;76(1):89 –91.\n29. Busacca M, Somigliana E, Bianchi S, De Marinis S, Calia C,\nCandiani M, Vignali M. Post-operative GnRH analogue treatment\nafter conservative surgery for symptomatic endometriosis stage\nIII–IV: a randomized controlled trial. Hum Reprod. 2001;16\n(11):2399–402.\n30. Parazzini F, Fedele L, Busacca M, Falsetti L, Pellegrini S, V enturini\nPL, Stella M. Postsurgical medical treatment of advanced endome-\ntriosis: results of a randomized clinical trial. Am J Obstet Gynecol.\n1994;171(5):1205–7.\n31. Hornstein MD, Hemmings R, Y uzpe AA, Heinrichs WL. Use of\nnafarelin versus placebo after reductive laparoscopic surgery for\nendometriosis. Fertil Steril. 1997;68(5):860 –4.\n32. V ercellini P , Crosignani PG, Fadini R, Radici E, Belloni C, Sismondi\nP . A gonadotrophin-releasing hormone agonist compared with ex-\npectant management after conservative surgery for symptomatic\nendometriosis. Br J Obstet Gynaecol. 1999;106(7):672–7.\n33. Gupta S, Goldberg JM, Aziz N, Goldberg E, Krajcir N, Agarwal A.\nPathogenic mechanisms in endometriosis-associated infertility.\nFertil Steril. 2008;90(2):247 –57.\n34.  de Ziegler D, Borghese B, Chapron C. Endometriosis and infertility:\npathophysiology and management. Lancet. 2010;376(9742):730–8.\nThis is an excellent review on endometriosis and infertility.\n35. Y oshida S, Harada T, Iwabe T, Taniguchi F, Mitsunari M, Y amauchi\nN, Deura I, Horie S, Terakawa N. A combination of interleukin-6 and\nits soluble receptor impairs sperm motility: implications in infertility\nassociated with endometriosis. Hum Reprod. 2004;19(8):1821–5.\n36. Perdichizzi A, Nicoletti F, La Vignera S, Barone N, D ’Agata R,\nVicari E, Calogero AE. Effects of tumour necrosis factor-alpha on\nhuman sperm motility and apoptosis. J Clin Immunol. 2007;27\n(2):152–62.\n37. Mansour G, Aziz N, Sharma R, Falcone T, Goldberg J, Agarwal A.\nThe impact of peritoneal fluid from healthy women and from\nwomen with endometriosis on sperm DNA and its relationship to\nthe sperm deformity index. Fertil Steril. 2009;92(1):61– 7.\n38. Gelbaya TA, Gordts S, D ’Hooghe TM, Gergolet M, Nardo LG.\nManagement of endometrioma pr ior to IVF: compliance with\nESHRE guidelines. Reprod Biomed Online. 2010;21(3):325 –30.\n39. Hughes E, Brown J, Collins JJ, Farquhar C, Fedorkow DM,\nV andekerckhove P . Ovulation suppression for endometriosis.\nCochrane Database Syst Rev. 2007;(3):CD000155.\n40. Benaglia L, Somigliana E, V ercellini P , Abbiati A, Ragni G, Fedele\nL. Endometriotic ovarian cysts negatively affect the rate of spon-\ntaneous ovulation. Hum Reprod. 2009;24(9):2183 –6.\n41. Tsoumpou I, Kyrgiou M, Gelbaya TA, Nardo LG. The effect of\nsurgical treatment for endometrioma on in vitro fertilization out-\ncomes: a systematic review and meta-analysis. Fertil Steril.\n2009;92(1):75–87.\n42. Kuivasaari P , Hippeläinen M, Anttila M, Heinonen S. Effect of\nendometriosis on IVF/ICSI outcome: stage III/IV endometriosis\nworsens cumulative pregnancy and live-born rates. Hum Reprod.\n2005;20(11):3130–5.\n43. Surrey ES, Silverberg KM, Surrey MW, Schoolcraft WB. Effect of\nprolonged gonadotropin-releasing hormone agonist therapy on the\noutcome of in vitro fertilization-embryo transfer in patients with\nendometriosis. Fertil Steril. 2002;78(4):699 –704.\nCurr Obstet Gynecol Rep (2012) 1:16 –24 23\n\n44. Sallam HN, Garcia-V elasco JA, Dias S, Arici A. Long-term pitu-\nitary down-regulation before in vitro fertilization (IVF) for women\nwith endometriosis. Cochran e Database Syst Rev. 2006;(1):\nCD004635.\n45. Kobayashi H, Sumimoto K, Moniwa N, Imai M, Takakura K,\nKuromaki T, Morioka E, Arisawa K, Terao T. Risk of developing\novarian cancer among women with ovarian endometrioma: a co-\nhort study in Shizuoka, Japan. Int J Gynecol Cancer. 2007;17\n(1):37–43.\n46.  Vlahos NF, Kalampokas T, Fotiou S. Endometriosis and ovarian\ncancer: a review. Gynecol Endocrinol. 2010;26(3):213 –9. This is a\nfull review of endometriosis and ovarian cancer .\n47.  Mandai M, Y amaguchi K, Matsumura N, Baba T, Konishi I.\nOvarian cancer in endometriosis: molecular biology, pathology,\nand clinical management. Int J Clin Oncol. 2009;14(5):383 –91.\nThis is a review of endometriosis-associated ovarian cancer in\nterms of molecular pathogenesis.\n48. LaGrenade A, Silverberg SG. Ovarian tumors associated with\natypical endometriosis. Hum Pathol. 1988;19(9):1080 –4.\n49. Ali-Fehmi R, Khalifeh I, Bandyopadhyay S, Lawrence WD, Silva\nE, Liao D, Sarkar FH, Munkarah AR. Patterns of loss of hetero-\nzygosity at 10q23.3 and microsatellite instability in endometriosis,\natypical endometriosis, and ovarian carcinoma arising in associa-\ntion with endometriosis. Int J Gynecol Pathol. 2006;25(3):223 –9.\n50. Y amaguchi K, Mandai M, Toyokuni S, Hamanishi J, Higuchi T,\nTakakura K, Fujii S. Contents of endometriotic cysts, especially\nthe high concentration of free iron, are a possible cause of carci-\nnogenesis in the cysts through the iron-induced persistent oxidative\nstress. Clin Cancer Res. 2008;14(1):32– 40.\n51. Mandai M, Matsumura N, Baba T, Yamaguchi K, Hamanishi J,\nKonishi I. Ovarian Clear Cell Carcinoma as a Stress-Responsive\nCancer: Influence of the Microenvironment on the Carcinogenesis\nand Cancer Phenotype. Cancer Lett. 2011;310(2):129 –33.\n52. Soliman NF, Hillard TC. Hormone replacement therapy in women\nwith past history of endometriosis. Climacteric. 2006;9(5):325 –35.\n53. Debus G, Schuhmacher I. Endometrial adenocarcinoma arising dur-\ning estrogenic treatment 17 years after total abdominal hysterectomy\nand bilateral salpingo-oophorectomy: a case report. Acta Obstet\nGynecol Scand. 2001;80(6):589–90.\n54. V an Gorp T, Amant F, Neven P , V ergote I, Moerman P . Endometriosis\nand the development of malignanttumours of the pelvis. A review of\nliterature. Best Pract Res ClinObstet Gynaecol. 2004;18(2):349–71.\n55. Kobayashi H, Sumimoto K, Kitanaka T, Yamada Y , Sado T, Sakata M,\nY oshida S, Kawaguchi R, Kanayama S, Shigetomi H, Haruta S, Tsuji\nY , Ueda S, Terao T. Ovarian endometrioma–risks factors of ovarian\ncancer development. Eur J Obstet Gynecol Reprod Biol. 2008;138\n(2):187–93.\n56. Alborzi S, Foroughinia L, Kumar PV , Asadi N, Alborzi S. A\ncomparison of histopathologic findings of ovarian tissue inadver-\ntently excised with endometrioma and other kinds of benign ovar-\nian cyst in patients undergoing laparoscopy versus laparotomy.\nFertil Steril. 2009;92(6):2004 –7.\n57. Jones KD, Fan A, Sutton CJ. The ovarian endometrioma: why is it\nso poorly managed? Indicators from an anonymous survey. Hum\nReprod. 2002;17(4):845 –9.\n58. Chapron C, Fauconnier A, Goffinet F, Bréart G, Dubuisson JB.\nLaparoscopic surgery is not inhe rently dangerous for patients\npresenting with benign gynaecologic pathology. Results of a\nmeta-analysis. Hum Reprod. 2002;17(5):1334 –42.\n59. Daraï E, Ballester M, Chereau E, Coutant C, Rouzier R, Wafo E.\nLaparoscopic versus laparotomic radical en bloc hysterectomy and\ncolorectal resection for endometriosis. Surg Endosc. 2010;24\n(12):3060–7.\n60. Hart RJ, Hickey M, Maouris P , Buckett W. Excisional surgery\nversus ablative surgery for ovarian endometriomata. Cochrane\nDatabase Syst Rev. 2008;(2):CD004992.\n61. Donnez J, Lousse JC, Jadoul P , Donnez O, Squifflet J. Laparoscopic\nm\nanagement of endometriomas using a combined technique of exci-\nsional (cystectomy) and ablative surgery. Fertil Steril. 2010;94\n(1):28–32.\n62. V ercellini P , Somigliana E, Viganò P , De Matteis S, Barbara G,\nFedele L. The effect of second-line surgery on reproductive per-\nformance of women with recurrent endometriosis: a systematic\nreview. Acta Obstet Gynecol Scand. 2009;88(10):1074 –82.\n24 Curr Obstet Gynecol Rep (2012) 1:16 –24","source_license":"CC0","license_restricted":false}