Endometriosis-Related Ovarian Cancer: Where Are We Now? A Narrative Review towards a Pragmatic Approach.

BACKGROUND: Endometriosis affects more than 10% of reproductive-aged women, causing pelvic pain and infertility. Despite the benign nature of endometriosis, ovarian endometriomas carry a higher risk of developing endometrioid carcinomas (EnOCs) and clear cell ovarian carcinomas (CCCs). Atypical endometriosis, defined as cytological atypia resembling intraepithelial cancer, is considered the precursor of endometriosis-associated ovarian cancer (EAOC). This narrative review aims to provide an overview of EAOC, proposing a practical approach to clinical and therapeutic decision making. METHODS: An electronic literature search was conducted from inception up to January 2023, using the MEDLINE database via PubMed to evaluate the existing literature on EAOC, including its pathogenesis, the diagnostic process, and the therapeutic possibilities, with articles not relevant to the topic or lacking scientific merit being excluded. RESULTS: Eighty-one articles were included in the review to present the current state of the art regarding EAOC. A pragmatic clinical flowchart is proposed to guide therapeutic decisions and improve patient outcomes. CONCLUSIONS: Endometriosis patients may have an increased risk of developing EAOC (either EnOC or CCC). Despite not being fully accepted, the concept of AE may reshape the endometriosis-ovarian cancer relationship. Further research is needed to understand the unaddressed issues.

Adenomyosis among patients undergoing postpartum hysterectomy for uncontrollable uterine bleeding: A multicenter, observational, retrospective, cohort study on histologically-based prevalence and clinical characteristics.

OBJECTIVE: To assess the prevalence of adenomyosis at pathologic examination, and its association with obstetric complications, peripartum maternal clinical characteristics and neonatal birth weight in patients undergoing postpartum hysterectomy due to postpartum hemorrhage (PPH). METHODS: A multicenter, observational, retrospective, cohort study was carried out including all women who underwent postpartum hysterectomy due to PPH at gestational week 23+0 or later, between January 2010 and May 2023. Patients were categorized into two groups based on the presence of adenomyosis at pathologic examination, and were compared for obstetric complications, peripartum maternal clinical characteristics, and neonatal birth weight. RESULTS: The histologically-based prevalence of adenomyosis in patients undergoing postpartum hysterectomy due to PPH was 39.4%. Adenomyosis was associated with a longer hospitalization time (regression coefficient: 4.43 days, 95% CI: 0.34-8.52, P = 0.034) and a higher risk of hypertensive disorders (OR: 5.82, 95% CI: 1.38-24.46, P = 0.016), threatened preterm labor (OR: 3.34, 95% CI: 1.08-10.31, P = 0.036), urgent/emergency C-section (OR: 24.15, 95% CI: 2.60-223.96, P = 0.005), postpartum maternal complications (OR: 4.96, 95% CI: 1.48-16.67, P = 0.012), maternal intensive care unit admission (OR: 3.56, 95% CI: 1.05-12.05, P = 0.041), and low birth weight neonates (OR: 3.8, 95% CI: 1.32-11.02, P = 0.013). CONCLUSION: In patients undergoing postpartum hysterectomy due to PPH, adenomyosis is a highly prevalent condition among, and is associated with adverse obstetric, maternal, and neonatal outcomes.

The role of hysteroscopy with morcellator without anesthesia in the management of abnormal uterine bleeding.

Objective: To evaluate the feasibility of hysteroscopy with morcellator without anesthesia and the diagnostic accuracy of 2D, 3D and power Doppler transvaginal sonography (TVS) in patients with abnormal uterine bleeding (AUB). Material and Methods: This was a retrospective study including women with AUB. All patients underwent 2D, 3D and power Doppler TVS evaluation of the uterine cavity, and patients with suspicion on ultrasound (US) of endometrial pathology (EP) underwent hysteroscopy with morcellator without anesthesia. The painful symptomatology was assessed during the procedure using a visual analogue scale (VAS). Additionally, histological evaluation was performed. Results: A total of 182 women underwent US imaging, of whom 131 (72%) had hysteroscopy. 130/131 patients completed the hysteroscopic examination with good compliance (VAS <4). One patient (0.8%) was unable to complete the procedure due to nulliparity and cervical stenosis. Of the 130 patients the US diagnosis was confirmed in 120 (92.3%), while in 10 patients (7.7%) the hysteroscopic diagnosis was different from the US diagnosis. Histological examination confirmed benign endometrial polyps in 115/130 patients (88.5%), while premalignant conditions were diagnosed in 3/130 patients (2.3%) and malignant conditions in 2/130 (1.5%). Of the 10 patients with endometrial thickening, two were diagnosed with a malignant condition. Conclusion: This study confirmed the feasibility of managing patients with AUB and suspicion of EP using "see-and-treat" hysteroscopy with morcellator without anesthesia. This procedure has the potential to yield desired outcomes while minimizing pain and discomfort, presenting a feasible outpatient approach for both treating and preventing endometrial carcinoma without requiring anesthesia.

Deep Infiltrating Endometriosis in Adolescence: Early Diagnosis and Possible Prevention of Disease Progression.

Endometriosis has a prevalence of 10% worldwide in premenopausal women. Probably, endometriosis begins early in the life of young girls, and it is commonly diagnosed later in life. The prevalence of deep infiltrating endometriosis (DIE) in adolescence is currently unknown due to diagnostic limits and underestimation of clinical symptoms. Dysmenorrhea is a common symptom in adolescents affected by DIE, often accompanied by dyspareunia and chronic acyclic pelvic pain. Ultrasonography-either performed transabdominal, transvaginal or transrectal-should be considered the first-line imaging technique despite the potential for missed diagnosis due to early-stage disease. Magnetic resonance imaging should be preferred in the case of virgo patients or when ultrasonographic exam is not accepted. Diagnostic laparoscopy is deemed acceptable in the case of suspected DIE not responding to conventional hormonal therapy. An early medical and/or surgical treatment may reduce disease progression with an immediate improvement in quality of life and fertility, but at the same time, painful symptoms may persist or even recur due to the surgery itself. The aim of this narrative review is to report the prevalence of DIE in adolescents, describe the pathogenetic theories and discuss the management in adolescent women, including the challenging road to diagnosis and the treatment alternatives.

The implications of the anatomy of the nerves and vessels in the treatment of rectosigmoid endometriosis.

Endometriosis is a common benign gynecological disease characterized by the presence of endometrial glands and stroma outside the uterus. It can be defined as endometrioma, superficial peritoneal endometriosis or deep infiltrating endometriosis (DIE) depending on the location and the depth of infiltration of the organs. In 5%-12% of cases, DIE affects the digestive tract, frequently involving the distal part of the sigmoid colon and rectum. Surgery is generally recommended in cases of obstructive symptoms and in cases with pain that is non-responsive to medical treatment. Selection of the most optimal surgical technique for the treatment of bowel endometriosis must consider different variables, including the number of lesions, eventual multifocal lesions, as well as length, width and grade of infiltration into the bowel wall. Except for some major and widely accepted indications regarding bowel resection, established international guidelines are not clear on when to employ a more conservative approach like rectal shaving or discoid resection, and when, instead, to opt for bowel resection. Damage to the pelvic autonomic nervous system may be avoided by detection of the middle rectal artery, where its relationship with female pelvic nerve fibers allows its use as an anatomical landmark. To reduce the risk of potential vascular and nervous complications related to bowel resection, a less invasive approach such as shaving or discoid resection can be considered as potential treatment options. Additionally, the middle rectal artery can be used as a reference point in cases of upper bowel resection, where a trans mesorectal technique should be preferred to prevent devascularization and denervation of the bowel segments not affected by the disease.

Diagnostic Accuracy of Ultrasound in the Diagnosis of Uterine Leiomyomas and Sarcomas.

BACKGROUND: Differential diagnosis between uterine leiomyomas and sarcomas is challenging. Ultrasound shows an uncertain role in the clinical practice given that pooled estimates about its diagnostic accuracy are lacking. OBJECTIVES: To assess the accuracy of ultrasound in the differential diagnosis between uterine leiomyomas and sarcomas. DATA SOURCES: A systematic review was performed searching 5 electronic databases (MEDLINE, Web of Sciences, Google Scholar, Scopus, and ClinicalTrial.gov) from their inception to June 2023. METHODS OF STUDY SELECTION: All peer-reviewed observational or randomized clinical trials that reported an unbiased postoperative histologic diagnosis of uterine leiomyoma or uterine sarcoma that also comprised a preoperative ultrasonographic evaluation of the uterine mass. TABULATION, INTEGRATION, AND RESULTS: Sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and area under the curve on summary receiver operating characteristic were calculated for each included study and as pooled estimate, with 95% confidence interval (CI); 972 women (694 with uterine leiomyomas and 278 with uterine sarcomas) were included. Ultrasound showed pooled sensitivity of 0.76 (95% CI, 0.70-0.81), specificity of 0.89 (95% CI, 0.87-0.92), positive and negative likelihood ratios of 6.65 (95% CI, 4.45-9.93) and 0.26 (95% CI, 0.07-1.0) respectively, diagnostic odds ratio of 23.06 (95% CI, 4.56-116.53), and area under the curve of 0.8925. CONCLUSIONS: Ultrasound seems to have only a moderate diagnostic accuracy in the differential diagnosis between uterine leiomyomas and sarcomas, with a lower sensitivity than specificity.

Diagnostic accuracy of MRI in the differential diagnosis between uterine leiomyomas and sarcomas: A systematic review and meta-analysis.

BACKGROUND: Differential diagnosis between uterine leiomyomas and sarcomas is challenging. Magnetic resonance imaging (MRI) represents the second-line diagnostic method after ultrasound for the assessment of uterine masses. OBJECTIVES: To assess the accuracy of MRI in the differential diagnosis between uterine leiomyomas and sarcomas. SEARCH STRATEGY: A systematic review and meta-analysis was performed searching five electronic databases from their inception to June 2023. SELECTION CRITERIA: All peer-reviewed observational or randomized clinical trials that reported an unbiased postoperative histologic diagnosis of uterine leiomyoma or uterine sarcoma, which also comprehended a preoperative MRI evaluation of the uterine mass. DATA COLLECTION AND ANALYSIS: Sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and area under the curve on summary receiver operating characteristic of MRI in differentiating uterine leiomyomas and sarcomas were calculated as individual and pooled estimates, with 95% confidence intervals (CI). RESULTS: Eight studies with 2495 women (2253 with uterine leiomyomas and 179 with uterine sarcomas), were included. MRI showed pooled sensitivity of 0.90 (95% CI 0.84-0.94), specificity of 0.96 (95% CI 0.96-0.97), positive likelihood ratio of 13.55 (95% CI 6.20-29.61), negative likelihood ratio of 0.08 (95% CI 0.02-0.32), diagnostic odds ratio of 175.13 (95% CI 46.53-659.09), and area under the curve of 0.9759. CONCLUSIONS: MRI has a high diagnostic accuracy in the differential diagnosis between uterine leiomyomas and sarcomas.

Extrauterine adenomyoma: A case report and systematic review of the literature.

OBJECTIVE: To describe a case of extrauterine adenomyoma (EA) and review all the cases of EA in the literature. METHODS: Pubmed/MEDLINE, Embase, and Google Scholar from 1807 to December 2022. All studies reporting the histologic diagnosis of an EA. We collected the following data: patient's age, size and location of adenomyoma, presence of endometriosis and adenomyosis, past gynecologic treatment, symptoms, diagnostic imaging, surgical intervention, alternative/adjuvant treatment, associated malignancy, and follow up. RESULTS: Sixty-seven studies with 85 patients were included. Pain was the most frequent symptom (69.5%). Among diagnostic examinations, ultrasonography was used in 60 out of 81 reported cases, with several radiologic features described. EA was located inside the pelvis in 77.6% of patients. Adnexa were the most frequent site of the disease (24, 28.2%). History of endometriosis or adenomyosis was described in 35 patients (35, 41.2%). Uterine tissue morcellation was reported in 6 of the 85 patients (7.1%). Associated malignancy was detected in 9 out of 85 patients with available data (10.6%). There were two recurrences of disease. CONCLUSION: Specific imaging features of EA are yet to be described in the literature. History of endometriosis and adenomyosis or uterine tissue morcellation may be suggestive of EA. Histologic examination can give a definitive diagnosis and exclude malignant transformation.

"In Situ" Methotrexate Injection Followed by Hysteroscopic Resection for Caesarean Scar Pregnancy: A Single-Center Experience.

BACKGROUND: We evaluated the efficacy of local methotrexate (MTX) treatment followed by hysteroscopic resection for caesarean scar pregnancy and its impact on future fertility. METHODS: Monocentric, prospective, observational study performed in the Haykel Hospital between June 2016 and December 2020. Twenty-one women with caesarean scar pregnancy underwent a transcutaneous ultrasound-guided direct injection of MTX into the gestational sac in an outpatient setting. Hysteroscopic resection of residual trophoblastic retention was then performed according to perisaccular blood flow. MAIN RESULTS: Two patients had complete spontaneous trophoblast expulsion after MTX injection, and hysteroscopy was performed in 19 patients for residual trophoblastic retention 1 to 12 weeks after MTX injection. Successful preservation of a healthy uterus with the combined procedure was obtained in 94.8% of patients. Hemostatic hysterectomy was required in one patient. Mean hospitalization duration was 1.5 days. Three patients had spontaneous pregnancy after the procedure. CONCLUSION: Direct MTX injection into the gestational sac for caesarean scar pregnancy followed by hysteroscopic resection was an effective technique with a short hospitalization, fertility preservation and a low major complication rate compared with other modalities of treatment reported in the literature. Further larger prospective comparative studies are needed to confirm the efficacy of this procedure.

Application of Deep Learning Model in the Sonographic Diagnosis of Uterine Adenomyosis.

BACKGROUND: This study aims to evaluate the diagnostic performance of Deep Learning (DL) machine for the detection of adenomyosis on uterine ultrasonographic images and compare it to intermediate ultrasound skilled trainees. METHODS: Prospective observational study were conducted between 1 and 30 April 2022. Transvaginal ultrasound (TVUS) diagnosis of adenomyosis was investigated by an experienced sonographer on 100 fertile-age patients. Videoclips of the uterine corpus were recorded and sequential ultrasound images were extracted. Intermediate ultrasound-skilled trainees and DL machine were asked to make a diagnosis reviewing uterine images. We evaluated and compared the accuracy, sensitivity, positive predictive value, F1-score, specificity and negative predictive value of the DL model and the trainees for adenomyosis diagnosis. RESULTS: Accuracy of DL and intermediate ultrasound-skilled trainees for the diagnosis of adenomyosis were 0.51 (95% CI, 0.48-0.54) and 0.70 (95% CI, 0.60-0.79), respectively. Sensitivity, specificity and F1-score of DL were 0.43 (95% CI, 0.38-0.48), 0.82 (95% CI, 0.79-0.85) and 0.46 (0.42-0.50), respectively, whereas intermediate ultrasound-skilled trainees had sensitivity of 0.72 (95% CI, 0.52-0.86), specificity of 0.69 (95% CI, 0.58-0.79) and F1-score of 0.55 (95% CI, 0.43-0.66). CONCLUSIONS: In this preliminary study DL model showed a lower accuracy but a higher specificity in diagnosing adenomyosis on ultrasonographic images compared to intermediate-skilled trainees.

Unilateral hydroureteronephrosis after introduction of a levonorgestrel-releasing intrauterine system: a case report and literature review.

Insertion of a LNG-Intra-uterine System (LNG-IUS) has many gynecological indications. The approved indications worldwide are contraception, treatment of abnormal uterine bleeding depending on not organic disease, and endometrial protection in case of an estrogenic therapy. Instead adenomyosis, fibroids, and fertility-sparing management of endometrial hyperplasia or early endometrial cancer in patients with desire of pregnancy are off label indications. Hydroureteronephrosis is an uncommon complication during LNG-IUS insertion. There are few cases described in the literature. The first diagnostic approach for this complication is an abdominal-pelvic ultrasound scan to identify the abnormal position of the device. Diagnostic management includes computed tomography (CT) or magnetic resonance imaging (MRI), which are necessary to confirm hydroureteronephrosis and to assess the exact location of the LNG-IUS in the abdomen. A minimally invasive approach is the standard of care with the removal of the device, while the therapeutic management of the hydroureteronephrosis depends on ureteral and kidney involvement. We report the history of a dislocated LNG-IUS in the left paracervical space with subsequent ipsilateral hydroureteronephrosis. In our case we removed the device through hysteroscopy and later inserted a J-J stent. Follow-up at three months revealed the persistence of left hydroureteronephrosis, so we performed ureter reimplantation. We also performed a review of the literature to analyze common diagnostic and therapeutic pathways for this rare complication.

Sonographic Assessment of Uterine Biometry for the Diagnosis of Diffuse Adenomyosis in a Tertiary Outpatient Clinic.

BACKGROUND: to compare several uterine biometric parameters at transvaginal ultrasound (TVUS) between adenomyosis and non-adenomyosis uteri and evaluate their role for the diagnosis of diffuse adenomyosis. METHODS: prospective observational study conducted between the 1 February 2022 and the 30 April 2022. In this case, 56 patients with TVUS diagnosis of adenomyosis were included. A 1:1 ratio age and parity-matched group of non-adenomyosis patients was selected. We compared sonographic uterine biometric parameters (longitudinal (LD), anteroposterior (APD) and transverse (TD) diameters, volume, simple and complex diameter ratios) and investigated their diagnostic performance. RESULTS: all sonographic parameters were significantly different between the study groups, except for TD/(LD+APD). Optimal cut-off values of APD and LD/APD showed the best sensitivity and specificity. APD diameter equal or superior to 39.5 mm (95% CI, 36.2-42.8) had sensitivity of 0.70 (95% CI, 0.57-0.80), specificity of 0.71 (95% CI, 0.59-0.82) and accuracy of 0.75 (95% CI, 0.66-0.84). LD/APD equal or inferior to 2.05 (95% CI, 1.96-2.13) showed sensitivity and specificity of 0.70 (95% CI, 0.57-0.80) each and accuracy of 0.72 (95% CI, 0.62-0.81). CONCLUSIONS: several biometric uterine parameters at TVUS in fertile-aged women were statistically different between adenomyosis and non-adenomyosis uteri, though their optimal cut-off values showed low accuracy in diagnosing adenomyosis.

Neonatal outcome in pregnancy hypotiroidee women.

To evaluate the impact that hypothyroidism may have on the course of pregnancy and on neonatal outcome. This cross-sectional study consisting of 160 pregnant women (60 with hypothyroidism and 100 as control) who had been hospitalized at the Obstetrics and Gynecology of the University of Siena. The obstetric visit, the collection of anamnestic data and serum concentrations of TSH, FT4 and AbTPO were performed for each woman. Stratification of the population into two groups based on the BMI showed that there is an average difference of -0.88 before pregnancy BMI between healthy women and hypothyroid women. Moreover, with regard to the obstetric history, 8.7 times higher risk of abortion was found in hypothyroid women. About the current pregnancy in hypothyroid women, slight fetal growth delay, increased risk of premature rupture of membranes (PROM), and a higher risk of developing hypertension and gestational diabetes had been found. The importance of a more detailed anamnesis should be evaluated with greater attention at the beginning of pregnancy. This, in order to avoid the risks related to a hypothyroidism condition during pregnancy and to establish an early therapeutic treatment appropriate to the metabolic demands of each patient.