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PubMed | Instituto Nazionale Tumori Fondazione G Pascale Irccs, Cannizzaro Hospital, Italian National Cancer Institute, University of Bari and 7 more.
Type: | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2016

Surgery followed by platinum-based chemotherapy is the standard of care for MOGCTs, except for stage IA dysgerminoma and stage IA grade 1 immature teratoma where surveillance only is recommended. The role of adjuvant chemotherapy and surgical staging is debated.Data from 144 patients with stage I MOGTs were collected among MITO centers (Multicenter Italian Trials in Ovarian Cancer) and analysed.55(38.2%) patients were affected by dysgerminomas, 49(34%) by immature teratomas, 26(18.1%) by yolk sac tumors and 14(9.7%) by mixed tumors. 73(50.7%) patients receive surgery plus chemotherapy, while 71 (49.3%) patients underwent surgery alone. The latter group included 32 dysgerminomas (14 IA-13 Ix, 3 IB, 2 IC), 34 immature teratomas (20 1A-13 IA grade 1, 6 Ix, 1 IB, 7 IC), 4 mixed tumors and 1 yolk sac tumor. 44 patients did not received chemotherapy, even if it would have been indicated by recommended approach. 94(65.3%) patients received peritoneal surgical staging. 23(15.9%) developed a recurrence. Incomplete surgical staging was associated with recurrence (p<0.05; OR 2.37) at Cox regression analysis. 7 patients died. 4 patients were affected by yolk sac tumors, 2 by mixed tumors and 1 by immature teratoma. 5 patients died for disease, 1 for acute leukemia and 1 for suicide. Prognostic parameters analyses showed that yolk sac component is a predictor for survival (p<0.05) Five-years OS rates were 96.8% and 88.7% in surgically staged and incomplete staged group, while 93.8% and 94.1% in standard treatment and in the surveillance group, respectively.This study shows that surveillance seems not to affect survival; chemotherapy should be reserved for relapse resulting in high cure rate. Incomplete peritoneal surgical staging is associated with recurrence. Yolk sac histology worsens the prognosis.


Scarfone G.,Gynecology and Neonatology | Bergamini A.,University of Milan | Noli S.,Gynecology and Neonatology | Villa A.,Gynecology and Neonatology | And 6 more authors.
Gynecologic Oncology | Year: 2014

Objective Endometrioid and clear cell ovarian tumors have been referred to as "endometriosis associated ovarian cancers". However, very few studies have compared clinical and prognostic features of endometriosis- associated cancers or cancers not associated with endometriosis according to specific histotypes. We have investigated clinical and histological features of the largest published series of clear cell ovarian cancers arising in endometriosis using a retrospective database. Methods Seventy three patients with a primary diagnosis of either pure clear cell ovarian cancer and mixed endometrioid-clear cell ovarian cancer have been divided into two groups according to the detection of cancer strictly arising from ovarian endometriosis or not (n = 27 and n = 46, respectively). Clinical and pathological data have been compared. Results Patients with clear cell carcinomas arising from endometriosis tend to be significantly younger (51.4 ± 10.0 and 58.4 ± 11.2 years, p = 0.02). FIGO stage, laterality, prevalence of pure versus mixed histology, and presence of synchronous endometrial carcinoma were not significantly different between the two groups. Unilateral ovarian involvement was more frequent in cases arising in endometriosis (85% vs 63%, p = 0.04). Ascites was not found in any of the endometriosis-associated cancer cases vs 19.5% in patients without endometriosis. The presence of endometriosis did not affect 5-year overall survival rates. Conclusions Endometriosis per se does not appear to be associated with a lower stage tumor or to predict prognosis in ovarian clear cell cancers. Unilateral involvement and reduced presence of ascites may be linked to the cystic nature of endometriosis which frequently presents as monolateral and in which associated tumors are more likely to be longer confined to the ovary before spreading. © 2014 Elsevier Inc.


Vigano P.,San Raffaele Scientific Institute | Corti L.,San Raffaele Scientific Institute | Berlanda N.,Gynecology and Neonatology
Fertility and Sterility | Year: 2015

The risk of pregnancy and neonatal complications in women with endometriosis and adenomyosis is debatable. A literature review looking at rates, presentation, and management of spontaneous hemoperitoneum, enlargement, abscess, and rupture of an endometrioma, uterine rupture, and bowel perforation in pregnant women with endometriosis was conducted. Moreover, studies addressing differences in early pregnancy (miscarriage), late pregnancy (gestational diabetes mellitus, preeclampsia, prematurity, placenta previa, placental abruption, cesarean section, hemorrhages) and neonatal outcomes (weight at birth) between endometriosis and adenomyosis patients versus control subjects were reviewed. The overall prevalence of endometriosis-related spontaneous hemoperitoneum in pregnancy is estimated to be ∼0.4%. Only four cases of endometrioma rupture in pregnancy have been reported. Although during pregnancy there is no way to anticipate the onset of complications from preexisting endometriosis, it is important, when a specific abdominal pain occurs, to suspect rare but potentially life-threating events. Population-based studies suggest a possible association of endometriosis with preterm birth and placenta previa. Limits of the published studies are noted and discussed. © 2015 Published by Elsevier Inc. on behalf of the American Society for Reproductive Medicine.


Sanchez,San Raffaele Scientific Institute | Vigano P.,San Raffaele Scientific Institute | Somigliana E.,Gynecology and Neonatology | Panina-Bordigno P.,San Raffaele Scientific Institute | And 4 more authors.
Human Reproduction Update | Year: 2014

background: Clinical data suggest that the presence of an ovarian endometrioma may cause per se damage to the surrounding otherwise healthy ovarian tissue. However, the basic research has so far done a limited job in trying to understand the potential detrimental effect of an endometrioma presence in the context of the ovarian physiology.We have reviewed the literature with the aim of characterizing the pathophysiology of the endometrioma focusing mostly on factors and mechanisms potentially affecting the surrounding, otherwise normal, ovarian tissue. methods: Comprehensive searches of PUBMED were conducted to identify human studies published from 1991 to 2013 in the English language on the cellular and molecular characterization of the various endometrioma components. results: An endometrioma contains free iron, reactive oxygen species (ROS), proteolytic enzymes and inflammatory molecules in concentrations from tens to hundreds of times higher than those present in peripheral blood or in other types of benign cysts. The cyst fluid causes substantial changes in the endometriotic cells that it baths from gene expression modifications to genetic mutations The physical barrier between the cyst contents and the normal ovarian tissue is a thin wall composed of the ovarian cortex itself or fibroreactive tissue.ROS potentially permeating the surrounding tissues and proteolytic substances degrading the adjacent areas are likely to cause the substitution of normal ovarian cortical tissue with fibrous tissue in which the cortex-specific stroma is reduced. The fibrosis is associated with smooth muscle metaplasia and followed by follicular loss and intraovarian vascular injury. Follicular density in tissue surrounding the endometriotic cyst was consistently shown to be significantly lower than in healthy ovaries but this pathological change does not appear to be caused by the stretching of surrounding tissues owing to the presence of a cyst. conclusions: There is sufficient molecular, histological and morphological evidence, in part deriving from knowledge of the pathophysiology, to support a deleterious effect of the endometrioma on the adjacent ovarian cortical tissue, independent of the mere mechanical stretching owing to its size. © The Author 2013.


Vigano P.,San Raffaele Scientific Institute | Somigliana E.,Gynecology and Neonatology | Panina P.,San Raffaele Scientific Institute | Rabellotti E.,San Raffaele Scientific Institute | And 3 more authors.
Human Reproduction Update | Year: 2012

Background: Endometriosis has been associated with specific morphometric characteristics and pigmentary traits. The purpose of this study was to systematically review prior publications dealing with this aspect in order to revisit phenotypic information in the context of phenomics principles. methods: Comprehensive searches of Pubmed, Medline and Embase were conducted to identify studies, published from 1990 to 2011 in the English language literature, on the relationship between endometriosis and morphometric characteristics/pigmentary traits. results: We identified 11 studies on the association between endometriosis and body mass index (BMI) in the adult population and 5 studies on the same association during early life. While a modest inverse correlation was found between endometriosis and adult BMI, a stronger association was consistently demonstrated between endometriosis and early life body size, even after adjusting for confounding factors such as age, birthweight, age at menarche, parity and oral contraceptive use. Four papers have been published on the association between endometriosis and cutaneous naevi and five on the association between the disease and specific pigmentary traits. A skin phenotype characterized by the presence of naevi and freckles and by a high sensitivity to sun exposure is represented more frequently in women with endometriosis. conclusions: Endometriosis appears to be associated with some phenotypic variations likely attributable to the strong effect of the environment on the expression and function of genes influencing the traits. Novel clues on endometriosis pathogenesis may derive from the analysis of the phenotypic traits associated with the disease. © The Author 2012. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Sanchez A.M.,San Raffaele Scientific Institute | Somigliana E.,Gynecology and Neonatology | Vercellini P.,Gynecology and Neonatology | Pagliardini L.,San Raffaele Scientific Institute | And 2 more authors.
Journal of Steroid Biochemistry and Molecular Biology | Year: 2016

Endometriosis is an estrogen-dependent chronic inflammatory condition that affects women in their reproductive period. Alterations in ovarian follicle morphology and function have been documented in affected women. The local intrafollicular environment has been as well examined by various groups. In the present review, we aimed to summarize the molecular evidence supporting the idea that endometriosis can negatively influence growth, steroidogenesis and the function of the granulosa cells (GCs). Reduced P450 aromatase expression, increased intracellular ROS generation and altered WNT signaling characterize the GCs of women with endometriosis. Clear evidence for an increased level of GC apoptosis has been provided in association with the downregulation of pro-survival factors. Other potentially negative effects include decreased progesterone production, locally decreased AMH production and lower inflammatory cytokine expression, although these have been only partially clarified. The possibility that endometriosis per se may influence IVF clinical results as a consequence of the detrimental impact on the local intrafollicular environment is also discussed. © 2015 Elsevier Ltd. All rights reserved.


Tandoi I.,San Raffaele Scientific Institute | Somigliana E.,Gynecology and Neonatology | Riparini J.,DMSD Ospedale San Paolo | Ronzoni S.,DMSD Ospedale San Paolo | And 2 more authors.
Journal of Pediatric and Adolescent Gynecology | Year: 2011

Objective: To evaluate rate and determinants of long-term recurrence of endometriosis in a population of young women. Design: Retrospective cohort study. Setting: University tertiary care referral center for women with benign gynecologic diseases. Participants: Young women undergoing first-line conservative surgery for endometriosis were eligible for the study. Data on age at surgery, disease stage, anatomical characteristics of endometriotic lesions, and endometriosis-related symptoms were collected. After diagnosis, patients were treated according to the standard care of the center. The protocol required all women to be followed up 1 month after surgery, and every 6 months afterward, with an interview to investigate persistence of symptoms, a clinical examination, and an ultrasound pelvic assessment. Results: Fifty-seven women aged ≤ 21 (mean age at diagnosis ± SD: 19.0 ± 1.1 years) entered the study. During a 5-year follow-up, 32 (56%, 95% confidence interval [CI]: 43%-68%) recurrences of endometriosis were diagnosed. A second laparoscopy to treat the recurrence was performed in 11 (34%) cases and confirmed the presence of the disease in all of them. In the remaining 21 (66%) cases, the recurrence was based on the reappearance of the symptoms or clinical or sonographic findings. The recurrence rate increased constantly with time from first surgery. No association emerged between recurrence rate and endometriosis-related symptoms, site/stage of the disease, type of surgery, and post-surgical medical treatment. Conclusions: The recurrence rate of endometriosis in young women appears higher than in older women. Since no determinants for recurrence have been detected among the factors examined, a profile of women at increased risk cannot be drawn. © 2011.


Candiani M.,IRCCS San Raffaele Hospital | Maddalena S.,IRCCS San Raffaele Hospital | Barbieri M.,Gynecology and Neonatology | Izzo S.,DMSD San Paolo | And 2 more authors.
Journal of Minimally Invasive Gynecology | Year: 2012

Study Objective: To assess changes in uterine and umbilical arteries during laparoscopy in human pregnancy. Design: Case series (Canadian Task Force classification III). Setting: University tertiary care referral center for high-risk pregnancy and minimally invasive surgery. Patients: Nine pregnant women who underwent first- and second-trimester laparoscopic surgery because of an adnexal mass. Intervention: Laparoscopic cyst enucleation or annessiectomy. Measurements and Main Results: No maternal complications and no miscarriages or adverse pregnancy outcome occurred. Mean (SD) gestational age at delivery was 39.1 (0.7) weeks, birth weight was 3390 (298) g, and Apgar score at 5 minutes was 9.6 (0.5). Mean uterine resistance index, umbilical artery pulsatility index, and fetal heart rate were measured using transvaginal ultrasonography at various times during surgery. Mean uterine resistance index and umbilical artery pulsatility index values remained constant during laparoscopy. Fetal heart rate was maintained in the normal range (120-160 bpm) but progressively decreased during the surgical procedure. Conclusion: In human pregnancy, laparoscopic techniques do not seem to modify uteroplacental perfusion evaluated using noninvasive ultrasonography. © 2012 AAGL.


Benaglia L.,Gynecology and Neonatology | Pasin R.,Gynecology and Neonatology | Pasin R.,University of Milan | Somigliana E.,Gynecology and Neonatology | And 5 more authors.
Human Reproduction | Year: 2011

BACKGROUND: There is a growing consensus that ovarian reserve is reduced after surgical excision of ovarian endometriomas. However, it remains to be fully clarified whether this damage precedes or follows surgery. In order to further elucidate this aspect, we evaluated ovarian responsiveness to hyperstimulation in women selected for IVF with unilateral unoperated endometriomas. The main aim of this study was to compare the number of developing follicles in the affected ovary with that in the contralateral intact gonad as a control. Methods Patients selected for IVF who were diagnosed with one or more monolateral endometriomas (diameter <4 cm) and who did not undergo previous ovarian surgery were retrospectively identified. We compared the number of follicles (diameter ≥11 mm) and the number of co-dominant follicles (diameter >15 mm) on the day of hCG administration in the affected and intact ovaries. Results Among the 84 women selected, the median interquartile range (IQR) number of follicles ≥11 mm in the affected and intact ovaries was 5 (3-7) and 5 (3-8), respectively (P = 0.36). The median (IQR) number of co-dominant follicles in the affected and intact ovaries was 3 (2-4) and 3 (2-5), respectively (P = 0.48). The number of co-dominant follicles was lower in the affected ovary in 36 cases (43%, 95% confidence interval: 32-53%). We also failed to identify any statistically significant difference between the two ovaries when evaluating data according to the number of cysts, their dimension, the dose of gonadotrophins used or the number of oocytes retrieved. CONCLUSIONS In women selected for IVF, the presence of an endometrioma does not markedly affect responsiveness to hyperstimulation. © The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Eller-Vainicher C.,University of Milan | Ossola M.W.,Gynecology and Neonatology | Beck-Peccoz P.,University of Milan | Chiodini I.,University of Milan
European Journal of Endocrinology | Year: 2012

A 35-year-old oriental woman, who was 32 weeks pregnant, was hospitalized with suspected preeclampsia. Subsequently, she developed stupor and lethargia. Biochemical assessment showed severe hypercalcemia (21 mg/dl) with undetectable parathyroid hormone (PTH) and markedly elevated PTH-related peptide (PTHrP) levels (26 pmol/l, normal values <1.1 pmol/l). The patientwas treated with i.v. fluid administration, which resulted in an unsatisfactory reduction in serum calcium. Therefore, a cesarean section was performed to deliver the baby. Serum calcium levels promptly normalized after delivery with undetectable PTHrP levels. She delivered a healthy infant only presenting with transient mild jaundice and slightly prolonged QT interval with serum calcium level of 7.8-8.4 mg/dl (corrected for albumin levels). In the subsequent days, the patient developed a transient 'hungry bone' syndrome (calcium 6.7 mg/dl, phosphorous 2.1 mg/dl, and PTH 100.4 pg/ml). In conclusion, this pregnant patient presented with PTHrP-associated hypercalcemia, presumably of placental origin. Delivery resulted in prompt reduction of serum calcium levels and a transient 'hungry bone' syndrome. © 2012 European Society of Endocrinology.

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