How to Manage Endometriosis in Adolescence: The Endometriosis Treatment Italian Club Approach.

The evaluation of endometriosis in an adolescent girl is a challenging topic. The initial stage of the disease and the limited diagnostic instrument appropriate for the youth age and for its typical features can reduce the ability of the gynecologist. At the same time, missing a prompt diagnosis can delay the beginning of specific and punctual management of endometriosis, which could avoid a postponed diagnosis from 6 to 12 years, typical of adolescent girls complaining of dysmenorrhea. This article aimed to answer all the potential questions around the diagnosis and management of endometriosis in adolescents starting from a clinical case looking at the possible solution that is easily reproducible in the clinical practice.

ART Innovations: Fostering Women's Psychophysical Health between Bioethics Precepts and Human Rights.

Infertility is a highly relevant global issue affecting the reproductive health of at least 15% of reproductive-aged couples worldwide. The scope and severity of the infertility problem is even more prevalent in developing countries, mostly due to untreated reproductive tract infections (RTIs). Infertility, however, goes beyond the mere inability to procreate, but brings about profound psychological, social, and ethical implications of enormous magnitude. In vitro fertilization (IVF) and other assisted reproduction technologies (ARTs) have gradually become widespread therapeutic options. After all, the implementation of medically assisted reproductive procedures in order to overcome infertility is in keeping with the tenets of the reproductive rights agenda laid out at the International Conference on Population and Development (ICPD) in Cairo in 1994. Nonetheless, concerns still linger about how to implement and regulate such interventions in an ethically tenable fashion. The unremitting pace at which such techniques develop have upset the very notion of sexuality relating to reproduction as well as the concept of family itself. That rift risks causing a crisis in terms of bioethics sustainability and enforcement, which is bound to happen when science and innovation outpace the bioethical precepts on which we rely for essential guidance in medical practice. The authors argue in favor of an approach to regulation and policy-making that puts on the forefront a thorough assessment as to potential risks that such interventions might entail for foundational bioethics principles and inalienable human rights.

hr-HPV testing in the management of women with ASC-US+ and in the follow-up of women with cytological abnormalities and negative colposcopy. Recommendations of the Italian group for cervical cancer screening (GISCi).

Compared to spontaneous screening, an organized screening programme is characterized by the presence of protocols and recommendations for all stages including follow-up. Despite the availability of well-functioning screening programmes throughout the country, the follow-up protocol after an abnormal Pap test and negative colposcopy is not clearly defined in Italy, and there is no uniformity of indications. HPV testing for oncogenic human papillomavirus (hr-HPV) has a high negative predictive value (NPV) and high positive predictive value (PPV) for CIN2+ and its employment can reduce follow-up assessments. In order to provide indications about the management of women with ASC-US+ and the follow-up of women with cytological abnormalities and negative colposcopy, a literature analysis was carried out, taking into consideration European and American guidelines and good practice recommendations from the most important scientific associations and regulatory agencies. GISCi (Italian Group for Cervical Screening) drafted recommendations for the management of women with ASC-US, L-SIL, ASC-H, AGC, and H-SIL until their return to the routine screening interval. This protocol can be applied not only in the management of abnormal Pap smears in cytology-based programmes, but also in the management of abnormal Pap test triage after HPV positive test when HPV is the primary screening test. The protocols approved within the screening programmes must have an extensive consensus among all involved professionals, including any that women might meet outside the programme.

Human papillomavirus prevalence in paired urine and cervical samples in women invited for cervical cancer screening.

With the introduction of Human papillomavirus (HPV) vaccination in young girls in 2007, it is important to monitor HPV infections and epidemiological changes in this target population. The present study has evaluated the detection of human papillomavirus DNA in paired cervical and urine samples to understand if HPV testing in urine could be used as non-invasive method to monitor HPV status in young women. The study enrolled 216 twenty five-year-old women, resident in Florence and invited for the first time to the cervical cancer Screening Program within a project evaluating the impact of HPV vaccination. HPV genotyping was performed on 216 paired urine and cervical samples. The overall concordance between cervix and urine samples, investigated by HPV genotyping (INNO-LiPA HPV Genotyping Extra), was: 85.6% (184/215), 84.6% (182/215), 80% (172/215) when the same HPV, at least the same HR HPV and all HR HPV, respectively, were detected. HPV type specific concordance in paired urine and cervical samples was observed in 85.8% (175/204) of women with normal cytology and in seven out of nine women with abnormal cytology. Urine seems to be a suitable and reliable biological material for HPV DNA detection as evidenced by the high concordance with HPV detected in cervical samples. These results suggest that urine could be a good noninvasive tool to monitor HPV infection in vaccinated women.

Participation and risk of high grade cytological lesions among immigrants and Italian-born women in an organized cervical cancer screening program in Central Italy.

Few studies analyzed the risk for high-grade squamous intraepithelial lesions or worse (HSIL+) among immigrants and natives attending organized cervical cancer (CC) screening programs (SP). We evaluated participation and diagnosis of HSIL+ by country of birth with logistic models. Overall 540,779 invitation letters were delivered to target women of Florence SP in three screening rounds (years 2000-2002, 2003-2005, 2006-2008). The probability of attending screening was lower for immigrants than natives, but the difference decreased from 35% (1st round) to 20% (2nd-3rd round) for women born in high migration pressure (HMP) countries. The risk of HSIL+ was double than natives for HMP-born women from countries with high prevalence of human papillomavirus, even adjusting for age and previous history of Pap test. This is an important public health problem due to an increasing proportion over time of immigrant women with a lower attendance and greater risk for CC.

Large-muscle endometriosis involving the adductor tight compartment: case report.

Extrapelvic endometriosis is an uncommon condition but can involve nearly every organ, resulting in a wide range of clinical manifestations. Herein, we describe the case of a 45-year-old woman not a candidate for hormonal therapy who had cyclic pain in the left thigh associated with progressive impairment of walking ability. Clinical, instrumental, and laboratory data supported the diagnosis of endometriosis involving the adductor muscles compartment associated with ovarian endometriomas. Laparoscopic bilateral salpingo-oophorectomy and local wide excision in collaboration with an experienced orthopedic oncologist were performed, and definitive histologic analysis confirmed the diagnosis of endometriosis. The patient was pain-free at 6-month follow-up and demonstrated substantial improvement in ambulation and quality of life. Large-muscle endometriosis is a rare entity that can compromise musculoskeletal integrity and decrease quality of life. In this case, surgical excision in collaboration with an orthopedic oncologist was the cornerstone of treatment.

The CXCR4/CXCL12 axis in endometrial cancer.

Chemokines and their receptors seem to act as important regulators of the metastatic cascade. CXCL12 and its receptor CXCR4 were shown to be involved in human cancer progression. There is increasing evidences suggesting that the expression of CXCR4 in human cancers is correlated with poor patient prognosis and that CXCR4 neutralization can prevent metastases in vivo. Here we tested the role of the CXCR4/CXCL12 axis in a neoplasia with a reduced risk of metastatic progression, such as human endometrial cancer. CXCR4 and CXCL12 mRNA expression was measured in 41 endometrial cancers and in corresponding not affected tissues. The expression of CXCR4 was predominant in endometrial cancer (P = 0.035) whereas CXCL12 was overexpressed in normal mucosae (P = 0.002). CXCR4 expression (P = 0.035), but not CXCL12, was significantly related to cancer differentiation. Endometrial cancer cells (HEC1A) were able to generate diffuse metastases in peritoneum, lung and liver of CD-1 nude mice, but the simultaneous treatment with a neutralizing anti-CXCR4 monoclonal antibody dramatically reduced the number and the size of metastases in the animals. In conclusion, our data seem to indicate that the CXCR4-CXCL12 axis can play a role in the progression of endometrial carcinoma and that specific therapies with antagonists of chemokines receptors could be of help in the treatment of metastatic patients.

Effect of levonorgestrel and mifepristone on endometrial receptivity markers in a three-dimensional human endometrial cell culture model.

OBJECTIVE: To investigate the effect of levonorgestrel and mifepristone on the expression of endometrial receptivity markers in a three-dimensional endometrial construct. DESIGN: In vitro study. SETTING: University hospital and research laboratory. PATIENT(S): Twelve fertile donors. INTERVENTION(S): Timed endometrial biopsy. MAIN OUTCOME MEASURE(S): Examine the effect of levonorgestrel along with another well-studied fertility-regulating drug, mifepristone, on the expression of endometrial receptivity factors in a three-dimensional stromal and epithelial cell coculture model by immunohistochemistry. RESULT(S): Both epithelial and stromal cells of in vitro endometrial construct showed the presence of estrogen receptor-alpha, estrogen receptor-beta, progesterone receptors-(A+B), vascular endothelial growth factor, leukemia inhibitory factor, interleukin-1 beta, and cyclooxygenase-2, whereas the expression of progesterone receptor-B (AR), integrin alpha(V)beta(3,) and MUC1 were confined to epithelial cells. Mifepristone up-regulated expression of epithelial estrogen receptor-beta and progesterone receptor-B and down-regulated stromal vascular endothelial growth factor and surface molecules MUC1 and integrin alpha(V)beta(3) as observed in vivo. Levonorgestrel had no effect on the expression of endometrial receptivity markers studied. CONCLUSION(S): This in vitro model expresses progesterone-regulated endometrial receptivity factors seen in the physiologic condition. Treatment with levonorgestrel did not affect the expression of these endometrial receptivity markers in contrast to mifepristone. This in vitro model holds the potential to study endometrial receptivity, the embryo-endometrial interaction, and develop new agents for fertility control.

Late solitary metastasis of cutaneous malignant melanoma presenting as abnormal uterine bleeding.

We present the case of a 52-year-old woman with a history of excised cutaneous malignant melanoma complaining of abnormal uterine bleeding 11 years after initial diagnosis. Hysteroscopic examination showed an endometrial lesion with polypoid shape and endometrial biopsy was suggestive for melanoma. After a complete clinical work-up ruling out other metastatic sites, the patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy. Final histopathological and immunohistochemical analysis confirmed the diagnosis of endometrial melanoma with initial myometrial invasion. After a 6-month follow-up period, the patient was disease free. Even after many years of negative follow up, gynecologists should be aware of the possibility that abnormal uterine bleeding could represent the clinical expression of metastatic melanoma in order to offer a prompt diagnosis and a personalized strategy of treatment.