Three Types of Endometriosis: Pathogenesis, Diagnosis and Treatment. State of the Art.

At present, there is no curative treatment for endometriosis. Medical management and surgical treatment do not provide long-term relief. A detailed understanding of its pathophysiology is mandatory in order to facilitate both the diagnosis and treatment. The delay that typically precedes proper diagnosis (6 to 7 years) is probably one of the most challenging aspects of endometriosis management. In 2012, the total cost per woman due to endometriosis was estimated to be 9579€ per year in a multicenter study across the USA and Europe. According to their physiopathology and their localization, ectopic endometrial lesions, consisting of endometrial glands and stroma, can be divided into three different types: superficial peritoneal endometriosis (SPE), ovarian endometrioma (OMA), and deep infiltrating endometriosis (DIE). The following paper aims to review the available data in the literature on the pathogenesis, diagnosis, and treatment of different types of endometriosis.

Endometriosis and Pregnancy: A Single Institution Experience.

Endometriosis may compromise the physiological course of pregnancy. The aim of this prospective observational study was to evaluate whether endometriosis causes a higher prevalence of obstetric and neonatal complications as well as a higher risk of caesarean section and to detect a possible correlation between the presence, type, and location of endometriosis and obstetric complications, previous surgery, and pregnancy outcome, as well as the influence of pregnancy on the course of the disease. We compared two cohorts of women with spontaneous pregnancy, with and without endometriosis. Obstetric and neonatal outcomes, mode of delivery, presence, type, and location of endometriotic lesions and the effect of pregnancy on the disease were analyzed. A total of 425 pregnancies were evaluated: 145 cases and 280 controls. Patients with endometriosis showed a higher incidence of miscarriage, threatened miscarriage, threatened preterm labor, preterm delivery, placental abruption, and a higher incidence of caesarean section. A significant correlation with pregnancy-induced hypertension and preeclampsia was found in the presence of adenomyosis. No difference in fetal outcome was found. One case of hemoperitoneum during pregnancy was observed. Pregnancy in women with endometriosis carries a higher risk of obstetric complications, such as miscarriage, threatened miscarriage, preterm labor, preterm birth, and a higher caesarean section rate. Endometriosis does not seem to influence fetal well-being.

Sonohysterosalpingography: Comparison of foam and saline solution.

PURPOSE: To compare sonohysterosalpingography (sono-HSG) with foam instillation (HyFoSy) versus saline solution (HyCoSy) in the evaluation of tubal patency. METHODS: We prospectively enrolled 37 infertile women, scheduled for laparoscopy. The women were randomized into two groups: HyFoSy (group I) and HyCoSy (group II). The patients of both groups underwent laparoscopy with dye test. We assessed the diagnostic performance (sensitivity, specificity, and overall accuracy) of HyFoSy and HyCoSy, compared with laparoscopy and dye test, in the assessment of tubal patency. RESULTS: Sono-HSG findings in tubal patency assessment obtained in the HyFoSy group were concordant with laparoscopic results in 94.4% of cases, with a sensitivity of 87.5% and a specificity of 100%, whereas in the HyCoSy group, concordance occurred in only 57.8% of examinations, with a sensitivity of 50% and a specificity of 66.6%. CONCLUSIONS: HyFoSy allows a more accurate diagnosis of tubal patency compared with HyCoSy. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:67-71, 2017.

Antibiotics Prophylaxis for Operative Hysteroscopy.

OBJECTIVE: To evaluate the incidence of infectious complications and effect of prophylactic antibiotic administration during operative hysteroscopic procedures. METHODS: A multicentric randomized controlled trial was conducted between January 2012 and December 2013. Women (n = 180) affected by endometrial hyperplasia, myomas, or endometrial polyps undergoing operative hysteroscopy were randomized to receive cefazolin 2 g intravenously 30 minutes prior to the procedure (n = 91) and no treatment (n = 89). RESULTS: No statistical difference in terms of postoperative fever (2.4% vs 2.3%, P = .99), endometritis (0% vs 0%), pain (6.0% vs 10.4%, P = .40), cervicitis-vaginitis (0% vs 0%), pelvic abscess (0% vs 0%), pelvic inflammatory disease (0% vs 0%), and bleeding (0% vs 0%) was noticed. No statistical difference in terms of side effects attributable to antibiotic prophylaxis such as allergy (0% vs 4.8%, P = .12), nausea (10.7% vs 17.4%, P = .27), vomiting (3.6% vs 4.6%, P = .99), diarrhea (4.8% vs 5.4%, P = .99), cephalea (9.5% vs 3.5%, P = .13), dizziness (4.8% vs 2.3%, P = .44), and meteorism (5.4% vs 3.4%, P = .99) was noticed. CONCLUSION: The results of the current study support the recommendation not to prescribe routine antibiotic prophylaxis prior to operative hysteroscopy.

Ixabepilone for the treatment of endometrial cancer.

INTRODUCTION: Endometrial cancer (EC) is the most common gynaecological cancer. Despite significant progress in the multimodality treatment approach, the prognosis remains poor for patients with advanced disease. Thus, there is the necessity of more effective strategies. The microtubule-stabilizing agent ixabepilone is the first drug in this new class of agents that has been approved for metastatic breast cancer treatment. Based on empiric data and on the clinical efficacy demonstrated in breast cancer, several clinical trials were proposed to define its role in EC. The aim of this review is to determine whether ixabepilone improved the clinical outcome in patients with locally advanced, recurrent or metastatic EC. AREAS COVERED: Preclinical and clinical studies of ixabepilone in endometrial cancer were analyzed and discussed. Data were obtained by searching for English peer-reviewed articles on PubMed, phase I and II studies registered on clincaltrials.gov, and related abstracts recently presented at major international congresses. EXPERT OPINION: Advanced or recurrent EC still represents a challenge and an unmet need in the panorama of gynaecological malignancies. Ixabepilone's future therapeutic role in EC remains ill defined. Nevertheless, despite its limited efficacy in EC, clinicians treating gynaecological tumours should be aware of its main aspects.

Adenomyosis: What the Patient Needs.

A panel of experts in the field of endometriosis expressed their opinions on management options in a 28-year-old patient, attempting pregnancy for 1 year, with severe cyclic pelvic pain and with clinical examination and imaging techniques suggestive of adenomyosis. Many questions this paradigmatic patient may pose to the clinician are addressed, and all clinical scenarios are discussed. A decision algorithm derived from this discussion is also proposed.

Restoring vaginal microbiota: biological control of bacterial vaginosis. A prospective case-control study using Lactobacillus rhamnosus BMX 54 as adjuvant treatment against bacterial vaginosis.

PURPOSE: Bacterial vaginosis (BV) is the most prevalent lower genital tract infection in reproductive-age women worldwide. BV is an ecological disorder of the vaginal microbiota characterized microbiologically by replacement of the lactobacilli, predominant vaginal microbiota. It is characterized by a high rate of relapse in sexual active women, and these patients show three or more relapses each year. A healthy vagina is characterized by hydrogen peroxide and acid-producing lactobacilli, which are crucial to maintain the physiological vaginal ecosystem and their depletion speeds up bacterial overgrowth with pH elevation, salidase and amine production, leading to the observed signs and symptoms of BV. The aim of this study is to evaluate the efficacy of long-term vaginal lactobacilli's implementation in restoring and maintaining vaginal microflora and pH and to collect data about prophylactic approach based on probiotics supplementation with lactobacilli. METHODS: This is a prospective case-control study, performed between January 2013 and September 2014 at Department of Gynecological Obstetrics and Urologic Sciences of "Sapienza" University of Rome. 250 non-pregnant sexually active women with diagnoses of BV were collected. Patients selected were divided in Group A (125 patients assigned to standard treatment for BV-metronidazole 500 mg orally twice a day for 7 days) and Group B (125 women undergoing the same standard antibiotic regimen followed by vaginal tablets containing Lactobacillus rhamnosus BMX 54). Patients were evaluated after 2, 6, and 9 months (T0, T2, T6, and T9) in term of recurrences rates of BV, vaginal symptoms, re-establishment of healthy vaginal flora, vaginal pH, and treatment tolerability. RESULTS: Vaginal flora was significantly replaced in Group B patients after 2 months comparing with Group A (p = 0.014). These data were confirmed at 6 and 9 months follow-up: patients that underwent prophylactic therapy with NORMOGIN(®) experienced significantly low rate of recurrences comparing with patients treated with antibiotics only (p < 0.001). During follow-up patients continuing supplementation had significant pH decrease respect to other patients (p < 0.001 at 9 months follow-up visit). CONCLUSIONS: Probiotic supplementation with vaginal Lactobacillus rhamnosus BMX54 seems to be useful in hindering bacteria growth especially after antibiotic therapy; therefore this intervention may be considered a new prophylactic treatment for preventing recurrence of BV, in particular in high-risk patients.

Cervical cancer: are there potential new targets? An update on preclinical and clinical results.

According to international guidelines, treatment of cervical cancer (CC) consists of surgery in early stages and of chemoradiation in locally advanced disease. Metastatic disease is usually treated with palliative chemotherapeutic regimens, but cytostatic drugs present significant side effects and show limited activity. Thus, the discovery of new anticancer agents, interfering with molecular targets expressed by the tumor's microenvironment or by the tumor cell itself, represents a possible chance for the struggle against this tumor. The aim of this review is to report all targets that have been investigated in preclinical and clinical studies. We discuss these potential targets according to "targeted therapies" NCI classification. The most investigated molecular targets have been epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), both involved in CC etiopathogenesis. Studies with anti-angiogenetic agents showed encouraging clinical efficacy and acceptable toxicity. Other interesting results have been obtained by immunotherapeutic strategies. Since biological characteristics of CC, especially in recurrent disease, are still partially unknown, future studies are necessary to understand mechanisms involved in CC carcinogenesis, in order to give to patients the most tailored and efficient treatments.

Nonabsorbable suture granuloma mimicking ovarian cancer recurrence at combined positron emission tomography/computed tomography evaluation: a case report.

INTRODUCTION: This is the first case of suture granuloma mimicking isolated ovarian cancer relapse. Only six analogous cases have been previously reported in other malignancies. CASE PRESENTATION: We report the case of a 44-year-old Caucasian woman with partially platinum-sensitive ovarian cancer in which radiological features, including computed tomography and combined 18F-fluorodeoxyglucose-positron emission tomography/computed tomography, were strongly suggestive of isolated cancer relapse in her right subdiaphragmatic region. Laparoscopic examination resulted negative, but was not completely suitable due to widespread adhesive syndrome. The laparotomy for secondary cytoreductive surgery and biopsy of the suspected area showed inflammatory granuloma caused by nonabsorbable propylene suture, without evidence of neoplastic cells. Moreover, unexpected peritoneal carcinosis was found. CONCLUSIONS: This evidence suggests that clinical details about previous surgical procedures are necessary for adequate interpretation. Although much progress has been made in imaging techniques, especially in the promising field of combined 18F-fluorodeoxyglucose positron emission tomography/computed tomography, these procedures should be still thoroughly investigated in order to promptly rule out tumor recurrence and avoid unnecessary surgery.

A promise in the treatment of endometriosis: an observational cohort study on ovarian endometrioma reduction by N-acetylcysteine.

Urged by the unmet medical needs in endometriosis treatment, often with undesirable side effects, and encouraged by N-acetylcysteine (NAC) efficacy in an animal model of endometriosis and by the virtual absence of toxicity of this natural compound, we performed an observational cohort study on ovarian endometriosis. NAC treatment or no treatment was offered to 92 consecutive Italian women referred to our university hospital with ultrasound confirmed diagnosis of ovarian endometriosis and scheduled to undergo laparoscopy 3 months later. According to patients acceptance or refusal, NAC-treated and untreated groups finally comprised 73 and 72 endometriomas, respectively. After 3 months, within NAC-treated patients cyst mean diameter was slightly reduced (-1.5 mm) versus a significant increase (+6.6 mm) in untreated patients (P = 0.001). Particularly, during NAC treatment, more cysts reduced and fewer cysts increased their size. Our results are better than those reported after hormonal treatments. Twenty-four NAC-treated patients-versus 1 within controls-cancelled scheduled laparoscopy due to cysts decrease/disappearance and/or relevant pain reduction (21 cases) or pregnancy (1 case). Eight pregnancies occurred in NAC-treated patients and 6 in untreated patients. We can conclude that NAC actually represents a simple effective treatment for endometriosis, without side effects, and a suitable approach for women desiring a pregnancy.

Olaparib, PARP1 inhibitor in ovarian cancer.

INTRODUCTION: Ovarian cancer is the most important cause of gynecological cancer-related mortality. Conventional treatments for advanced or recurrent disease offer limited results in terms of long-term responses and survival. Researches have recently focused on target therapies, which represent a new, promising, therapeutic approach, able to maximizing tumor kill and minimizing toxicity. The family of polyadenosine diphosphate-ribose polymerase (PARP) inhibitors is currently one of the most hopeful and investigated alternatives. AREAS COVERED: Preclinical and clinical studies of Olaparib , the most investigated PARP inhibitor in ovarian cancer, are analyzed and discussed. Data were obtained by searching for all English peer-reviewed articles on Medline, on Cochrane Database and all on-going Phase I and II studies registered on National Cancer Institute Clinical Trials; also any related abstracts recently presented on Olaparib at major international congresses will be included. EXPERT OPINION: Bad prognosis and drug resistance usually affect ovarian cancer. Recent trends toward the knowledge of molecular-specific pathways have produced new target drugs. PARP inhibition mediated by Olaparib in BRCA1 (breast cancer 1) and BRCA2 (breast cancer 2)-mutated and in sporadic ovarian cancer represents a promising field of investigation. Further studies are needed to confirm initial exciting results.