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• W2138444015 abstract "Ovarian tissue inadvertently excised along with endometriomas was associated with the presence of pericystic fibrosis and serum levels of CA-125, representing the only clinical parameter for predicting follicle loss before surgery. A consecutive series of 91 ovarian endometriotic cysts were studied, and an inverse relationship between serum CA-125 and the thickness of the fibrotic tissue of the endometrioma capsule was demonstrated. Ovarian tissue inadvertently excised along with endometriomas was associated with the presence of pericystic fibrosis and serum levels of CA-125, representing the only clinical parameter for predicting follicle loss before surgery. A consecutive series of 91 ovarian endometriotic cysts were studied, and an inverse relationship between serum CA-125 and the thickness of the fibrotic tissue of the endometrioma capsule was demonstrated. Endometriosis, a relatively common disease that is often associated to pelvic pain, is a direct cause of multiple operations and infertility (1Giudice L.C. Kao L.C. Endometriosis.Lancet. 2004; 364: 1789-1799Abstract Full Text Full Text PDF PubMed Scopus (2437) Google Scholar). Although this disease has been known for long time, the pathogenesis remains elusive, and the optimal treatment is disputed (2Donnez J. Chantraine F. Nisolle M. The efficacy of medical and surgical treatment of endometriosis-associated infertility: arguments in favour of a medico-surgical approach.Hum Reprod Update. 2002; 8: 89-94Crossref PubMed Scopus (61) Google Scholar, 3Garry R. Diagnosis of endometriosis and pelvic pain.Fertil Steril. 2006; 86: 1307-1309Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar). Ovarian endometriosis is one of the most common manifestations of the disease, affecting about 50% of women with endometriosis. Laparoscopic excision is widely accepted as the gold standard approach for the management of endometriosis (4Garry R. The effectiveness of laparoscopic excision of endometriosis.Curr Opin Obstet Gynecol. 2004; 16: 299-303Crossref PubMed Scopus (123) Google Scholar), although concerns have arisen from histologic observations (5Muzii L. Bianchi A. Bellati F. Cristi E. Pernice M. Zullo M.A. et al.Histologic analysis of endometriomas: what the surgeon needs to know.Fertil Steril. 2007; 87: 362-366Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar, 6Brosens I.A. Van Ballaer P. Puttemans P. Deprest J. Reconstruction of the ovary containing large endometriomas by an extraovarian endosurgical technique.Fertil Steril. 1996; 66: 517-521Abstract Full Text PDF PubMed Scopus (84) Google Scholar). It has been reported that cyst excision by laparoscopic stripping technique implies a loss of ovarian tissue surrounding the endometrioma capsule, removed along with the cyst (5Muzii L. Bianchi A. Bellati F. Cristi E. Pernice M. Zullo M.A. et al.Histologic analysis of endometriomas: what the surgeon needs to know.Fertil Steril. 2007; 87: 362-366Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar). Excessive removal of ovarian tissue also may lead to an impaired responsiveness to ovarian hyperstimulation treatments (7Ragni G. Somigliana E. Benedetti F. Paffoni A. Vegetti W. Restelli L. et al.Damage to ovarian reserve associated with laparoscopic excision of endometriomas: a quantitative rather than a qualitative injury.Am J Obstet Gynecol. 2005; 193: 1908-1914Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar). Recently, we reported that capsules of ovarian endometriomas more frequently showed fibrosis than nonendometriotic cysts and that the ovarian tissue inadvertently excised along with the endometrioma wall was associated with the presence of pericystic fibrosis (8Vicino M. Resta L. Scioscia M. Marzullo A. Ceci O. Bettocchi S. Correlation between serum levels of Ca125 and follicular loss after laparoscopic cystectomy in women with ovarian endometrioma.J Minim Invasive Gynecol. 2007; 14: 223-227Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar). Additionally, serum levels of CA-125 represented the only clinical parameter able to predict follicle loss before surgery (8Vicino M. Resta L. Scioscia M. Marzullo A. Ceci O. Bettocchi S. Correlation between serum levels of Ca125 and follicular loss after laparoscopic cystectomy in women with ovarian endometrioma.J Minim Invasive Gynecol. 2007; 14: 223-227Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar). Although serum levels of CA-125 are not always correlated with the spread or severity of endometriotic lesions, it has been proposed to be related to the activity of the disease (9Toki T. Kubota J. Lu X. Nakayama K. Immunohistochemical analysis of CA125, CA19-9, and Ki-67 in stage III or IV endometriosis: positive correlation between serum CA125 level and endometriotic epithelial cell proliferation.Acta Obstet Gynecol Scand. 2000; 79: 771-776PubMed Google Scholar). Our study assessed the relationship between serum levels of CA-125 and both cyst wall thickness and the thickness of the fibrotic tissue of the endometrioma capsule. A consecutive series of 76 premenopausal women with ovarian endometriosis was studied. The endometrioma wall was evaluated histologically on multiple sections in 91 ovarian endometriotic cysts. The laparoscopic excision of endometriotic ovarian cysts (by the stripping technique) and the histologic preparations were previously described elsewhere (8Vicino M. Resta L. Scioscia M. Marzullo A. Ceci O. Bettocchi S. Correlation between serum levels of Ca125 and follicular loss after laparoscopic cystectomy in women with ovarian endometrioma.J Minim Invasive Gynecol. 2007; 14: 223-227Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar). The thickness of the cyst wall and its fibrotic part (Fig. 1A) were measured three times using a micrometer, and the mean value was recorded. The relationship between wall thickness and fibrosis with serum levels of CA-125 was assessed by means of Spearman correlation (as independent factors) and one-way analysis of variance (ANOVA) between groups on raw and clustered data, respectively. Power analysis indicated that the power was 0.95 with a alpha of 0.05 and a population standard deviation of 0.1. Data were analyzed using GraphPad InStat (version 3.0; GraphPad Software Inc., San Diego, CA). P<.05 was considered statistically significant. Fourteen women (18.4%) presented with multiple endometriomas with a lump sum of diameters of all cysts of 4.9 ± 2.1 cm. The capsule wall thickness was similar in small (≤4 cm) and large (>4 cm) cysts (2.0 ± 0.8 mm vs. 2.1 ± 0.6 mm, respectively). No difference was found between these groups for serum CA-125 levels (37.9 ± 28.2 IU/mL vs. 42.7 ± 25.2 IU/mL). Higher levels of CA-125 were found in cases with thinner fibrotic tissue in the cyst wall (see Fig. 1E; P<.001), and an inverse correlation was also demonstrated (see Fig. 1F; r2=0.14 and P=.001). Histologically, the endometrioma wall appears as endometriotic tissue surrounded by fibrosis and a rim of ovarian tissue (5Muzii L. Bianchi A. Bellati F. Cristi E. Pernice M. Zullo M.A. et al.Histologic analysis of endometriomas: what the surgeon needs to know.Fertil Steril. 2007; 87: 362-366Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar). Hachisuga and Kawarabayashi (10Hachisuga T. Kawarabayashi T. Histopathological analysis of laparoscopically treated ovarian endometriotic cysts with special reference to loss of follicles.Hum Reprod. 2002; 17: 432-435Crossref PubMed Scopus (171) Google Scholar) reported that two different types of endometriomas could be identified during the stripping technique. An easy removal was described for endometriotic cysts that presented with extensive fibrosis of the capsule. Therefore, the interface between the fibrotic capsule and the normal ovarian tissue may represent the plane of cleavage that is being developed during the surgical excision by the stripping procedure. The penetration of endometriotic tissue into the cyst wall was found to be directly correlated with the total cyst wall thickness, demonstrating that the fibrotic component increased as the endometriosis deepened (5Muzii L. Bianchi A. Bellati F. Cristi E. Pernice M. Zullo M.A. et al.Histologic analysis of endometriomas: what the surgeon needs to know.Fertil Steril. 2007; 87: 362-366Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar). The serum CA-125 level was reported to correlate with endometriotic epithelial cell proliferation (9Toki T. Kubota J. Lu X. Nakayama K. Immunohistochemical analysis of CA125, CA19-9, and Ki-67 in stage III or IV endometriosis: positive correlation between serum CA125 level and endometriotic epithelial cell proliferation.Acta Obstet Gynecol Scand. 2000; 79: 771-776PubMed Google Scholar), which represents an indicator of the activity of the disease. On the basis of these observations, it is likely that the tendency to penetration of endometriotic cells into the capsule is related to the proliferative activity of these cells that cover the internal surface of the cyst (5Muzii L. Bianchi A. Bellati F. Cristi E. Pernice M. Zullo M.A. et al.Histologic analysis of endometriomas: what the surgeon needs to know.Fertil Steril. 2007; 87: 362-366Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar). Therefore, our findings may suggest that at early stages the capsule is still thin and the intense proliferative activity of endometriotic epithelial cells induces higher levels of CA-125. Subsequently, the endometriotic penetration into the capsule wall enhances fibrosis, and the process tends to slacken (increased wall thickness with higher fibrosis and reduced levels of CA-125). The actual origin of endometriomas is still elusive, and little is known about its natural history (1Giudice L.C. Kao L.C. Endometriosis.Lancet. 2004; 364: 1789-1799Abstract Full Text Full Text PDF PubMed Scopus (2437) Google Scholar, 5Muzii L. Bianchi A. Bellati F. Cristi E. Pernice M. Zullo M.A. et al.Histologic analysis of endometriomas: what the surgeon needs to know.Fertil Steril. 2007; 87: 362-366Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar). The significant delay in diagnosis (11Matsuzaki S. Canis M. Pouly J.L. Rabischong B. Botchorishvili R. Mage G. Relationship between delay of surgical diagnosis and severity of disease in patients with symptomatic deep infiltrating endometriosis.Fertil Steril. 2006; 86: 1314-1316Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar) certainly has contributed to our limited knowledge. The histologic features of the endometrioma wall may contribute to our unraveling of the physiopathology of these lesions. It is conceivable that pericystic fibrosis is secondary to the proliferative and inflammatory processes related to endometriosis itself. This may explain why CA-125 levels are so high in ovarian carcinomas (high cellular proliferation) but are not elevated in all cases with advanced endometriosis, when perhaps it has stabilized (9Toki T. Kubota J. Lu X. Nakayama K. Immunohistochemical analysis of CA125, CA19-9, and Ki-67 in stage III or IV endometriosis: positive correlation between serum CA125 level and endometriotic epithelial cell proliferation.Acta Obstet Gynecol Scand. 2000; 79: 771-776PubMed Google Scholar). Besides, penetration of endometriotic cells deep into the capsule enhance the generation of fibrotic tissue (5Muzii L. Bianchi A. Bellati F. Cristi E. Pernice M. Zullo M.A. et al.Histologic analysis of endometriomas: what the surgeon needs to know.Fertil Steril. 2007; 87: 362-366Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar). Our findings support these hypotheses; assuming that cysts with a thin fibrotic tissue are “younger” and have more intense biological activity (proliferation and inflammation) may explain the higher levels of serum CA-125. These histologic data provide theoretic support for a medicosurgical approach to endometriotic cysts, especially when the serum CA-125 level is high. In these cases, the possibility of medical therapy before surgery has to be considered (12Royal College Obstetrics and Gynaecology Guideline 41. Initial management of chronic pelvic pain. RCOG, London2004Google Scholar). The efficacy of medical therapy in the treatment of pelvic pain (13Ballard K. Lowton K. Wright J. What's the delay? A qualitative study of women's experiences of reaching a diagnosis of endometriosis.Fertil Steril. 2006; 86: 1296-1301Abstract Full Text Full Text PDF PubMed Scopus (317) Google Scholar) and for reducing serum levels of CA-125 (14Franssen A.M. van der Heijden P.F. Thomas C.M. Doesburg W.H. Willemsen W.N. Rolland R. On the origin and significance of serum CA-125 concentrations in 97 patients with endometriosis before, during, and after buserelin acetate, nafarelin, or danazol.Fertil Steril. 1992; 57: 974-979Abstract Full Text PDF PubMed Google Scholar) in cases of endometriosis is widely recognized. A direct correlation between follicular loss and serum levels of CA-125 has been reported (8Vicino M. Resta L. Scioscia M. Marzullo A. Ceci O. Bettocchi S. Correlation between serum levels of Ca125 and follicular loss after laparoscopic cystectomy in women with ovarian endometrioma.J Minim Invasive Gynecol. 2007; 14: 223-227Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar), and this may reflect a thinner fibrotic component of the cyst capsule. Surgery may be put off until the endometriosis is “stabilized” (reduced serum CA-125); a thick capsule ensures an easier surgical removal of the cyst because its wall is mostly fibrotic." @default.
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• W2138444015 title "Fibrotic tissue in the endometrioma capsule: surgical and physiopathologic considerations from histologic findings" @default.
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