Risk of endometrial malignancy in women treated for breast cancer: the BLUSH prediction model - evidence from a comprehensive multicentric retrospective cohort study.

OBJECTIVE: This study aimed to evaluate characteristics of endometrial surveillance in women treated for breast cancer to build a clinical prediction model. DESIGN: A multicentric retrospective cohort study was conducted at two tertiary-care university hospitals from January 2020 to June 2023. Perimenopausal and postmenopausal women treated for breast cancer were categorized into two groups: patients with and without diagnosis of endometrial malignancy (endometrial carcinoma) or premalignancy (atypical endometrial hyperplasia). Characteristics of breast cancer and ultrasonographic and hysteroscopic examinations were compared. A prediction model for endometrial malignancy was built using logistic regression. Predictive accuracy was assessed using the receiver operating characteristic (ROC) curve and goodness of fit using the Hosmer-Lemeshow test. RESULTS: One hundred and thirty-two (28 with premalignancy or malignancy and 104 without malignancy) women were analyzed. A nomogram was produced for prediction model development utilizing the presence and duration in months of abnormal uterine (BL)eeding, ultrasound (US) vascular pattern and echogenicity and (H)ysteroscopic appearance of endometrium (BLUSH) as determined by logistic regression. Sensitivity and specificity were 79.17% and 95.19%, respectively, with an area under ROC curve of 0.965, indicating good accuracy. Good goodness of fit and prediction stability were indicated by the calibration curve and Hosmer-Lemeshow test (χ2 = 26.36; p = 0.999). CONCLUSIONS: Breast cancer survivors undergoing endometrial surveillance might benefit from a potentially useful prediction model based on hysteroscopic appearance, ultrasonographic uniformity of endometrium, Doppler flow and presence of abnormal uterine bleeding.

Combined Robotic Transanal Transection Single-Stapled Technique in Ultralow Rectal Endometriosis Involvement Associated With Parametrial and Vaginal Infiltration.

OBJECTIVE: To describe a combined robotic and transanal technique used to treat ultralow rectal endometriosis in a 36-year-old patient with multiple pelvic compartments, which was responsible for infertility, dyspareunia, left sciatic pain, and severe dyschezia. DESIGN: Surgical video article. SETTING: The achievement of a perfect bowel anastomosis in patients with low rectal endometriosis could be challenging owing to technical and anatomic limitations [1]. By allowing a right angle rectotomy with a single-stapled anastomosis, the transanal transection single-stapled technique overcomes these technical difficulties ensuring a good-quality anastomosis with an easier correction of postoperative anastomotic leakage when it occurs [2,3]. INTERVENTIONS: The surgery starts by splitting the nodule in 3 components according to different anatomic structures involved (parametrium, vagina, and rectum). Parametrial and vaginal fragments are excised as previously described (Supplemental Videos 1) [4]. The rectal involvement is approached following several steps: isolation and cut of inferior mesenteric vessels (inferior mesenteric artery and inferior mesenteric vein) and left colic artery to obtain a proper colon mobilization; transanal rectotomy immediately below the lower limit of the nodule; extraction of the specimen through the anus (Supplemental Videos 2); proximal bowel segment transection 1 cm above the upper limit of the nodule; introduction of circular stapler anvil into the sigmoid colon; placement of 2 purse string to secure the anvil and at distal rectal cuff, respectively; connection of the anvil to the shoulder of circular stapler; stapler closing and firing with coloanal anastomosis formation; stapled line reinforcement by stitching; and integrity anastomosis test (Supplemental Videos 3). No preventive diverting stoma was performed in accordance with our policy [5]. CONCLUSIONS: Although no data are yet available in patients with endometriosis, the use of transanal transection single-stapled technique may be an interesting approach in patients with very low rectal endometriosis involvement.

Safety, Efficacy, and Cost-effectiveness of Organ Suspension in Laparoscopic Gynecologic Surgery: A Retrospective Cohort Study to Validate an Innovative Technique: Laparoscopic Organ Suspension sec. Angioni.

OBJECTIVES: This study aims to evaluate the safety, efficacy, and cost-effectiveness of the Laparoscopic Organ Suspension (OS) sec. Angioni, an innovative approach to transient OS in laparoscopic gynecological procedures. Recognizing the need to enhance surgical site access and overcome limitations of existing organ retraction methods, the study investigates a novel, in-theater constructed OS device. DESIGN: This retrospective observational study was conducted from March 2019 to May 2021 and included 330 patients who underwent multiport or single-site-port laparoscopic surgery employing Angioni's technique for transient pelvic OS. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants included individuals undergoing surgery for conditions such as endometriosis, ovarian cancer, endometrial cancer, pelvic prolapse, and benign ovarian cysts. The Laparoscopic OS sec. Angioni utilizes a segment of a Foley catheter connected to a Polyglactin suture to provide adjustable tension, minimizing the need for reconfiguration during surgery. RESULTS: The application of this OS technique resulted in an average suspension time of 1.9 min, with no significant difference between senior and junior surgeons. The method proved more time-efficient for posterior peritoneum suspension than other published methods and showed no additional risks of organ damage, bleeding, conversion to laparotomy, or OS-related complications. The secondary outcomes revealed reduced hospital stays and minimal blood loss, highlighting the procedure's overall efficiency. LIMITATIONS: Given its retrospective and single-center nature, the study's results may not be widely generalizable. Prospective multicentric comparative studies are recommended to further validate Angioni's technique. CONCLUSIONS: Laparoscopic OS sec. Angioni is introduced as a straightforward, safe, and cost-effective method that significantly streamlines the surgical process. Its adaptability and ease of use suggest that it could be a valuable addition to current gynecological surgical practices, with potential implications for increasing efficiency and reducing procedural costs. Future studies are required to confirm these results across diverse clinical environments.

Fertility, pregnancy and perioperative outcomes after operative hysteroscopy for uterine septum: a network meta-analysis.

INTRODUCTION: Septate uterus is a congenital malformation associated with adverse reproductive and pregnancy outcomes. It remains controversial whether hysteroscopic septoplasty should be recommended for the treatment of septate uterus, and it is also unclear if different hysteroscopic methods have more favorable outcomes. This study aims to compare the available hysteroscopic techniques of septoplasty for fertility, reproductive, and perioperative outcomes. METHODS: This systematic review and meta-analysis was conducted following PRISMA guidelines. We searched Medline, Scopus, and Cochrane databases up to April 2023 without language restrictions. Eligible studies had to compare two or more different methods of hysteroscopic septoplasty in women with septate uterus and report on fertility and pregnancy outcomes after a follow-up. Perioperative outcomes were also examined. Data extraction was performed by two independent reviewers using a standardized form. Risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Form and Revised Cochrane risk-of-bias tool (RoB 2). RESULTS: Out of 561 studies identified, 9 were included in the systematic review and meta-analysis. The comparison of different hysteroscopic septoplasty techniques based on the energy used showed higher pregnancy rates after mechanical septoplasty in comparison to electrosurgery, while miscarriage and live birth rates were comparable. Laser vs. electrosurgery and mechanical techniques of septoplasty had comparable pregnancy, miscarriage, and live birth rates. The network meta-analysis after comparing every different method used showed significantly higher clinical pregnancy rate in scissor group in comparison to resectoscope. No significant differences were found among the techniques regarding miscarriage rate and live birth rate. CONCLUSION: In summary, this systematic review and network meta-analysis suggests that hysteroscopic septoplasty with scissors is associated with higher pregnancy rates compared to resectoscope. However, the limited evidence available and small sample sizes in the included studies indicate that these findings should be interpreted with caution. Further studies are required to determine the effectiveness of various hysteroscopic techniques and guide clinical decision-making in the management of this condition.

C-section technique vs minilaparotomy after minimally invasive uterine surgery: a retrospective cohort study.

PURPOSE: Uterine leiomyomas are benign uterine tumors. The choice of surgical treatment is guided by patient's age, desire to preserve fertility or avoid "radical" surgical interventions such as hysterectomy. In laparotomy, the issue of extracting the fibroid from the cavity does not arise. However, in laparoscopy and robotic surgery, this becomes a challenge. The aim of the present study was to determine the optimal surgical approach for fibroid extraction following laparoscopic or robotic myomectomy in terms of postoperative pain, extraction time, overall surgical time, scar size, and patient satisfaction. METHODS: A total of 51 patients met the inclusion criteria and were considered in our analysis: 33 patients who had undergone the "ExCITE technique" (Group A), and 18 patients a minilaparotomy procedure (Group B), after either simple myomectomy, multiple myomectomy, supracervical hysterectomy, or total hysterectomy. The diagnosis of myoma was histologically confirmed in all cases. RESULTS: Regarding the postoperative pain evaluation, at 6 h, patients reported 4 [3-4] vs 6 [5.3-7] on the VAS in Group A and B, as well as at 12 h, 2 [0-2] vs 3.5 [2.3-4] in Group A and B, respectively: both differences were statistically significant (p < 0.001). No statistically significant difference at 24 h from surgery was found. All patients in Group A were satisfied with the ExCITE technique, while in Group B only 67% of them. The length of the hospital stay was significantly shorter in Group A as compared to Group B (p = 0.007). In terms of the operative time for the extraction of the surgical specimen, overall operative time, and the scar size after the surgery, there was a statistically significant difference for those in Group A. CONCLUSION: The ExCITE technique does not require specific training and allows the surgeon to offer a minimally invasive surgical option for patients, with also an aesthetic result. It is a safe and standardized approach that ensures tissue extraction without the need for mechanical morcellation.

Hysteroscopic diode laser myolysis: from a case series to literature review of incisionless myolysis techniques for managing heavy menstrual bleeding in premenopausal women.

PURPOSE: This case series examined the safety and effectiveness of hysteroscopic myolysis using laser-induced interstitial thermo-therapy (LITT) for treating heavy menstrual bleeding (HMB) in premenopausal women with FIGO type 1 or 2 uterine fibroids, not planning for future fertility. Additionally, a comprehensive review of innovative, minimally invasive, incisionless myolysis techniques was conducted. METHODS: Women with HMB, sonographically diagnosed with a single FIGO type 1 or 2 fibroid, underwent hysteroscopic myolysis using the Leonardo® diode laser. Effectiveness was assessed via transvaginal ultrasound measurement of myoma size, volume and vascularization pre and post-procedure. Moreover, we also evaluated any improvements in symptoms using the Pictorial Blood Loss Assessment Chart (PBAC score) scores. RESULTS: The procedure resulted in significant HMB reductions and noticeable fibroid size, volume, and vascularization decrease in all three patients, with no reported complications. The literature review revealed both advantages and limitations of the minimally invasive, incisionless myolysis techniques. CONCLUSIONS: Hysteroscopic laser myolysis is a safe and effective therapeutic intervention for patients experiencing HMB, diagnosed with FIGO type 1 or 2 fibroids, and not planning for future fertility. The procedure resulted in significant reductions in menstrual blood loss and fibroid size. Despite the promising results, it is essential to note the limitations of this report, including its case series design, a small number of patients, and a short follow-up period. Further research is necessary to confirm these results.

Hysteroscopy: where did we start, and where are we now? The compelling story of what many considered the "Cinderella" of gynecological endoscopy.

Hysteroscopy has truly revolutionized the field of diagnostic and operative gynecology. It is presently regarded as the gold standard method for both the diagnosis and treatment of intrauterine diseases and it has fundamentally altered the way gynecologists treat patients with such conditions. These pathologies can now be diagnosed and treated in an outpatient setting, thanks to technological advancements and instrument downsizing. Two hundred years of development and notable innovation are now reflected in the present hysteroscopic practice. This review attempts to trace the boundaries-pushing history of hysteroscopy by highlighting the advancements in technology and the therapeutic and diagnostic benefits offered by this groundbreaking approach.

Uterine cervical stenosis: from classification to advances in management. Overcoming the obstacles to access the uterine cavity.

BACKGROUND: To date hysteroscopy is the gold standard technique for the evaluation and management of intrauterine pathologies. The cervical canal represents the access route to the uterine cavity. The presence of cervical stenosis often makes entry into the uterine cavity difficult and occasionally impossible. Cervical stenosis has a multifactorial etiology. It is the result of adhesion processes that can lead to the narrowing or total obliteration of the cervical canal. PURPOSE: In this review, we summarize the scientific evidence about cervical stenosis, aiming to identify the best strategy to overcome this challenging condition. METHODS: The literature review followed the scale for the quality assessment of narrative review articles (SANRA). All articles describing the hysteroscopic management of cervical stenosis were considered eligible. Only original papers that reported data on the topic were included. RESULTS: Various strategies have been proposed to address cervical stenosis, including surgical and non-surgical methods. Medical treatments such as the preprocedural use of cervical-ripening agents or osmotic dilators have been explored. Surgical options include the use of cervical dilators and hysteroscopic treatments. CONCLUSIONS: Cervical stenosis can present challenges in achieving successful intrauterine procedures. Operative hysteroscopy has been shown to have the highest success rate, particularly in cases of severe cervical stenosis, and is currently considered the gold standard for managing this condition. Despite the availability of miniaturized instruments that have made the management of cervical stenosis more feasible, it remains a complex task, even for experienced hysteroscopists.

Hysteroscopy and weight loss in treatment of endometrial cancer: case report and literature review.

Fertility-sparing treatments have become important for young women with atypical endometrial hyperplasia (AEH) or endometrial carcinoma (EC) who wish to preserve their reproductive potential. Evidence indicates a strong relationship between weight and EC and the effect of weight loss on reducing the risk of EC. We report the case of a young obese woman with a body mass index (BMI) of 46.6 kg/m2, diagnosed with grade 2 endometrial endometrioid adenocarcinoma, who underwent a combined fertility-sparing treatment with hysteroscopic resection followed by insertion of a levonorgestrel intrauterine system. After twelve months of failure to achieve a complete response, bariatric surgery was proposed to lose weight and improve the response to treatment. Histologic regression was achieved three months after surgery, with a weight loss of 30 kg and fifteen months after combined treatment of endometrial cancer. We reviewed the literature to summarize the evidence on the role of bariatric surgery and weight loss in modifying the oncologic and reproductive outcomes of women undergoing fertility-sparing treatment for atypical endometrial lesions.

Association of vitamin D deficiency and vitamin D receptor (VDR) gene single-nucleotide polymorphism (rs7975232) with risk of preeclampsia.

BACKGROUND: Preeclampsia has a multifactorial-yet-elusive etiology. Recent reports suggest a link between preeclampsia and vitamin D (VD) metabolic axis. Genetic variations like single-nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) gene can alter the metabolic role of VD, which have been shown by several genetic association studies. However, there is discordance among these studies. OBJECTIVE: The current study aimed to investigate the association of VDR gene polymorphism (ApaI) and VD deficiency with risk of developing preeclampsia. PATIENTS AND METHOD: In this case-control study, 40 preeclamptic and 40 normotensive pregnant women were compared for VD status and VDR gene polymorphism. Serum 25-hydroxyvitamin-D [25(OH) D] level was determined by enzyme-linked immunosorbent assay (ELISA) and VDR gene polymorphism Apa1 was analyzed by Allele specific polymerase chain reaction (AS-PCR) using sequence specific primers. RESULTS: Serum levels of 25(OH) D were very low but comparable in both preeclamptic and normotensive pregnant women. The difference between the two groups were not statistically significant (p = .423). VDR gene polymorphism ApaI (rs7975232) was found not to have significant association with the risk of developing preeclampsia. The frequencies of wild genotype (GG) in preeclamptic and normotensive women were 27.5% and 22.5% respectively. A total of 25% of preeclamptic women had mutant homozygous genotype (TT) and 17.5% of normotensive women had mutant homozygous genotype. The frequency of mutant heterozygous genotype (GT) in preeclamptic patients was 47.5% and in normotensive women was 60%. The variation of wild and mutant genotypes between the two groups was not statistically significant (p > .05). CONCLUSION: This study showed that VDR gene polymorphism (ApaI) and VD deficiency are not associated with the risk of preeclampsia.

Effects of different progesterone levels on reproductive outcomes in assisted reproductive technologies: from molecular basis to treatment strategies.

PURPOSE: The aim of this narrative review is to offer an overview about the role of progesterone levels on pregnancy outcome in patients undergoing assisted reproductive technologies (ARTs). METHODS: A detailed computerized search of the literature was performed in the main electronic databases (MEDLINE, EMBASE, Web of Science) to determine the importance of elevated progesterone levels at different stages of the cycle for pregnancy rates in the in vitro fertilization (IVF) cycle. Our review also provides information on the differences between elevated progesterone levels and their interpretation in normal and in poorly responding women. RESULTS: After careful evaluation, our search strategy yielded a total of 15 included articles, showing the possible factors that may have had an impact on the increased progesterone level before human chorionic gonadotropin (HCG) injection and the different thresholds above which the pregnancy rate was lower. Furthermore, increased progesterone on cycle day 2 or 3 could serve as a marker for increased progesterone in the late follicular phase, which is associated with a lower pregnancy rate. CONCLUSION: Despite the literature data that support the negative effect of elevated progesterone on fresh cycles, due to lack of randomized controlled trials, the value of measuring progesterone in daily practice is questionable. Available evidence supports the detrimental effect of elevated progesterone in different subgroups of women, although there is still the need for defining different thresholds and durations of high progesterone exposure. The need for various thresholds for different cohorts of women, the inter-assay variability is making this decision harder.

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.

Efficacy of Hysteroscopy in Improving Fertility Outcomes in Women Undergoing Assisted Reproductive Technique: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Usefulness of hysteroscopy before assisted reproductive technique (ART) was considered debatable. However, over the last decade, several new trials have been added to available literature. We aimed to assess the impact of diagnostic and operative hysteroscopy on reproductive outcomes of infertile women with and without intrauterine abnormalities. MATERIALS AND METHODS: MEDLINE, Scopus, SciELO, Embase, Cochrane Library at CENTRAL, PROSPERO, CINAHL, grey literature, conference proceedings, and international controlled trials registries were searched without temporal, geographical, or language restrictions. Randomized controlled trials (RCTs) of infertile women comparing hysteroscopy versus no hysteroscopy prior to the first ART or after at least one failed attempt were included. RCTs of infertile women with intrauterine pathology comparing diagnostic versus operative hysteroscopy were included in separate analysis. Random-effect meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Grading of Recommendations, Assessment, Development and Evaluation and Cochrane criteria were used for quality of evidence and risk of bias assessment. Primary outcome was live birth rate (LBR). Secondary outcomes were clinical pregnancy (CPR) and pregnancy loss rate. RESULTS: Fifteen studies (5,038 women) were included. Compared to no hysteroscopy before first or after failed ART attempts, moderate-quality evidence showed that hysteroscopy increased the LBR (relative risk [RR] 1.24, 95% confidence interval [CI] 1.09-1.43, I2 = 21%), confirmed by subgroup analysis for women with failure after one or more ART cycles (RR 1.43, 95% CI: 1.19-1.72, I2 = 0%) but not before the first ART. Moderate-quality evidence showed that it increased the CPR (RR 1.36, 95% CI: 1.18-1.57; I2 = 51%), confirmed in subgroup analysis for both implantation failure (RR 1.40, 95% CI: 1.12-1.74, I2 = 52%) and before first ART (RR 1.32, 95% CI: 1.11-1.57, I2 = 42%). Low-quality data suggest that operative hysteroscopy increases CPR when used to treat intrauterine pathologies (RR 2.13, 95% CI: 1.56-2.92, I2 = 0%). CONCLUSIONS: Although moderate-quality evidence supports performing hysteroscopy before ART in women with history of implantation failure, hysteroscopic evaluation of uterine cavity should be considered a first-line technique in all infertile women undergoing ART. Additional high-quality RCTs are still needed, particularly to assess yield during couple's initial evaluation even before ART is considered.

Hysteroscopic versus histopathological agreement in the diagnosis of chronic endometritis: results from a retrospective observational study.

PURPOSE: To evaluate the agreement rate between hysteroscopy and pathological examination in case of chronic endometritis. METHODS: A retrospective observational study carried out at Gynecology and Obstetrics Department, Puerta de Hierro Hospital, Autónoma University of Madrid, Spain, from January 2021 to June 2022 was performed by obtaining data from 115 medical records of women who underwent office hysteroscopies that was compared with the findings of final histological examination of endometrial biopsy. Cohen's kappa index was used to evaluate this agreement rate. In addition, sensitivity, specificity, positive and negative predictive value and diagnostic accuracy were obtained. RESULTS: The agreement between hysteroscopic findings and histological examination showed a modest result with a Cohen's kappa index of 34%. In addition, we obtained a specificity of 70% and a sensitivity of 64%. The positive and negative predictive value were 60.8% and 73.4%, respectively. An excellent agreement rate (100%) between histological and hysteroscopic results was observed in presence of hyperemia and micropolyps. CONCLUSION: Although the sample size is not as large as that of other studies published so far, the first glance of our experience is that hysteroscopic signs are not yet sufficient to make an accurate diagnosis of chronic endometritis, thus requiring a histopathological confirmation to make it.

Hysteroscopy in the new media: quality and reliability analysis of hysteroscopy procedures on YouTube™.

BACKGROUND: Hysteroscopy plays a crucial role in diagnosing and managing various intrauterine pathologies. However, its execution can be influenced by patients' perception and understanding, which are often shaped by digital resources such as YouTubeTM. Given its popularity and accessibility, YouTubeTM has the potential to greatly influence patients' knowledge and expectations about this procedure, highlighting the need for accurate and reliable information. PURPOSE: This study aims to assess the reliability and quality of hysteroscopy information available to patients on YouTubeTM. Understanding the nature of information patients' access can help address their fears and potential misunderstandings about the procedure, consequently reducing the likelihood of suspension or postponement due to anxiety. METHODS: A comprehensive analysis of YouTubeTM was conducted, simulating the search process of a patient seeking information about hysteroscopy. The study evaluated the reliability and quality of 90 out of the first 100 hysteroscopy-related videos on YouTubeTM, scored by four gynecologists-two experienced hysteroscopists and two trainees. The videos were assessed for reliability and quality using the mDISCERN and Global Quality Scale (GQS) scores. RESULTS: The average mDISCERN and GQS scores for the evaluated videos were below the optimal three points, highlighting the lack of fluency, comprehensiveness, and reliability of the available information. Notably, while videos produced by experts, including doctors and professional channels, had higher scores, they still fell short of the minimum score of 3. These videos also were not considered more suitable for either patients or trainees. Videos that were assessed as reliable (mDISCERN ≥ 3) were observed to be longer and were more frequently produced by doctors. These videos were suggested more to trainees rather than patients. Similarly, videos deemed as fluent and comprehensive (GQS ≥ 3) were longer and were more often recommended to patients. CONCLUSIONS: While YouTubeTM is a widely used source of medical information, the quality and reliability of hysteroscopy videos on the platform are poor. The strategic use of selected, high-quality hysteroscopy videos can enhance procedure success and alleviate patient fears. However, the unsupervised discovery of information by patients could potentially lead to procedure failure or an elevated level of stress due to misleading or incorrect information.

"Better late than never but never late is better", especially in young women. A multicenter Italian study on diagnostic delay for symptomatic endometriosis.

PURPOSE: The aim of the study was to assess the length of diagnostic delay of symptomatic endometriosis in Italy and analyse the presence of correlations between the socio-demographic status of patients and the clinical characteristics/type of diagnosis. MATERIALS AND METHODS: This multicenter cross-sectional questionnaire-based study was conducted in 10 tertiary Italian referral centres for diagnosis and treatment endometriosis. A total of 689 respondents with histologically proven endometriosis and onset of the disease with pain symptoms completed an on-line self-reported questionnaire written in their own language (World Endometriosis Research Foundation-Endometriosis Phenome and Biobanking Harmonisation Project-Endometriosis Patient Questionnaire-Minimum) evaluating endometriosis related symptoms, family history of endometriosis and chronic pelvic pain, demographic data, as well as medical, reproductive, and obstetric history. RESULTS: The mean diagnostic delay found was of 11.4 years. The mean time (14.8 years) from symptoms onset to diagnosis was significantly longer among patients aged 9-19 vs patients aged 20-30 (mean 6.9 years, p < 0.001) and patients aged 31-45 (mean 2.9, p < 0.001). No significant association were found between a delayed diagnosis and any of the clinically relevant factors such as the number or severity of the reported symptoms, familiarity, hormonal therapy intake or methodology of diagnosis. CONCLUSIONS: The mean diagnostic delay of endometriosis in Italy is about 11 years. The delay can be up to 4 years longer in patients with pain symptoms onset under 20 years. Educating clinicians and patients on pathologic nature of endometriosis related pelvic pain is advisable to reduce waiting time to diagnosis, especially for young women.

Diode laser use in hysteroscopic surgery: current status and future perspectives.

Recent advances in surgical technology and innovative techniques have revolutionized surgical gynecology, including transcervical hysteroscopic procedures. Surgical lasers (Nd-Yag, Argon, diode, and CO2 lasers) have been promoted to remove a variety of gynecological pathologies. For hysteroscopic surgery, the diode laser represents the most versatile and feasible innovation, with simultaneous cut and coagulate action, providing improved hemostasis compared with CO2 laser. The newest diode laser devices exhibit increased power and a dual wavelength, to work precisely with reduced thermal dispersion and minimal damage to surrounding tissues. Their efficacy and safety have been validated both in the hospitals as well as in the office setting. Updated evidence reports that several hysteroscopic procedures, including endometrial polypectomies, myomectomies and metroplasties can be successfully performed with a diode laser. Therefore, this review aimed to give a deeper understanding of the role of laser energy in gynecology and subsequently in hysteroscopy in order to safely incorporate this technology into clinical practice.

PAX8 Positivity, Abnormal p53 Expression, and p16 Negativity in a Primary Endometrial Squamous Cell Carcinoma: A Case Report and Review of the Literature.

Primary endometrial squamous cell carcinoma (PESCC) is a rare entity. As the clinicopathologic features and the immunophenotype have not been completely defined yet, here we report our experience and review of the literature on this topic. A 73-yr-old nulliparous woman presented with pelvic pain and vaginal bleeding. Endometrial biopsy showed a carcinoma with squamous differentiation infiltrating the myometrium. Total hysterectomy with bilateral salpingo-oophorectomy and selective pelvic lymphadenectomy was performed. Definitive diagnosis was squamous carcinoma of the endometrium, with one lymph node metastasis (stage IIIC1). Immunohistochemistry evidenced immunoreactivity of the tumor cells for cytokeratin 5, p63, cytokeratin 7, PAX8, PTEN, and cyclin D1, aberrant p53 overexpression, and Ki-67 reactivity in ~70% of the tumor cells. Estrogen and progesterone receptor, PAX2, WT1, and p16 were negative. Our case was the first PAX8-positive PESCC in the literature, underlining the Mullerian system origin of this neoplasm. Abnormal p53 expression of this case confirmed its role in the pathogenesis of PESCC. Further studies on a large number of cases are needed to better understand the pathologic features and the immunophenotype of PESCC.

State of the art, new treatment strategies, and emerging drugs for non-hormonal treatment of endometriosis: a systematic review of randomized control trials.

Objective: The aim of this systematic review is to recap the data obtained from randomized controlled trials looking at new pharmacologic treatments for endometriosis published over the last decade with a focus on non-hormonal therapeutic options alleviating endometriosis-associated pelvic pain.Methods: We identified relevant original studies in the English language through a search of the MEDLINE, Scopus, and EMBASE (2012 to present) databases using the appropriate MeSH terms and applying the article type filter 'randomized controlled trials'. A total of 179 records were found during the electronic search. After a detailed evaluation and review of the manuscripts, seven primary articles met the inclusion criteria. A systematic review of the data was conducted.Results: This review included several, non-hormonal emerging drug therapies for endometriosis-associated pelvic pain. Based on our results, we divided well-founded studies into three subgroups: antiangiogenic agents, immunomodulators, and natural components. Randomized control trials showed promising results with dopamine agonists (cabergoline, quinagolide, and bromocriptine), and the immunomodulatory JNK inhibitor bentamapimod. Agents that have not been represented in randomized control trials or have failed to demonstrate efficacy include statins and TNF-α inhibitors.Conclusion: Although there are substantial improvements in non-hormonal therapy options, majority of the currently available treatment options are supressive rather than curative and do not present a final solution for patients. Future research priorities should be to identify novel target therapies and to evalute the effects of available drugs through different routes of administration.

Current status and challenges of drug development for hormonal treatment of endometriosis: a systematic review of randomized control trials.

OBJECTIVE: The aim of this systematic review is to summarize the data obtained from randomized controlled trials looking at new pharmacologic treatments for endometriosis published over the last decade with a focus on hormonal therapeutic options for endometriosis-associated pelvic pain (EAPP), excluding studies focusing on fertility. METHODS: We identified relevant original studies in the English language through a search of the MEDLINE, Scopus, and EMBASE (2012 to present) databases using the appropriate MeSH terms and applying the article type filter 'randomized controlled trials'. A total of 219 records were found during the electronic search. After a detailed evaluation and review of the manuscripts, 11 primary articles met the inclusion criteria. A systematic review of the data was conducted. RESULTS: This review included several emerging drug therapies for EAPP. Randomized control trials showed promising results with several oral gonadotropin-releasing hormone antagonists (elagolix, relugolix, ASP1707, linzagolix). However, studies of other hormonal agents such as aromatase inhibitors and selective progesterone receptor modulators have not yielded significant or new advantages. Selective estrogen receptor modulators have not been represented in randomized control trials and have failed to demonstrate clinical efficacy. CONCLUSION: Although numerous novel agents are being investigated for the treatment of endometriosis, there is still no significant progress in the development of curative rather than suppressive drugs. Therefore, further efforts are needed to develop an effective and hopefully curative treatment for this chronic, costly, and overwhelming disease.