"From the tip to the deep of the iceberg": Parametrial involvement in endometriosis.

Deep endometriosis (DE) can be localized in the parametrium, a complex bilateral anatomical structure, sometimes necessitating intricate surgical intervention due to the potential involvement of autonomic nerves, uterine artery, and ureter. If endometriotic ovarian cysts have been considered metaphorically representative of "the tip of the iceberg" concerning concealed DE lesions, it is reasonable to assert that parametrial lesions should be construed as the most profound region of this iceberg. Also, based on a subdual clinical presentation, a comprehensive diagnostic parametrial evaluation becomes imperative to strategize optimal management for patients with suspected DE. Recently, the ULTRAPARAMETRENDO studies aimed to evaluate the role of transvaginal ultrasound for parametrial endometriosis, showing distinctive features, such as a mild hypoechoic appearance, starry morphology, irregular margins, and limited vascularization. The impact of medical therapy on parametrial lesions has not been described in the current literature, primarily due to the lack of adequate detection at imaging. The extension of DE into the parametrium poses significant challenges during the surgical approach, thereby increasing the risk of intra- and postoperative complications, mainly if performed by centers with low expertise and following multiple surgical procedures where parametrial involvement has gone unrecognized. Over time, the principles of nerve-sparing surgery have been incorporated into the surgical DE treatment to minimize iatrogenic damage and potentially reduce the risk of functional complications.

Ultrasonographic characterization of parametrial endometriosis: a prospective study.

OBJECTIVE: To study the ultrasonographic diagnostic accuracy and characteristics of parametrial endometriosis comprehensively. DESIGN: This prospective study enrolled patients with suspected deep endometriosis (DE) scheduled for laparoscopic surgical treatment. Preoperative ultrasonographic examinations were performed following the International Deep Endometriosis Analysis criteria. This study aimed to evaluate the presence of parametrial endometriosis and its ultrasonographic characteristics, using surgical diagnosis as the reference standard. Additionally, indirect signs of DE and concomitant DE nodules associated with parametrial involvement were identified, assessing their predictive significance in the anterior, lateral, and posterior parametrial areas. SETTING: Referral institution for endometriosis. PATIENTS: Patients with suspected DE scheduled for surgical treatment. INTERVENTIONS: Standardized preoperative ultrasonographic examination. MAIN OUTCOME MEASURES: The diagnostic accuracy of transvaginal ultrasound in identifying parametrial endometriosis, including sensitivity and specificity, and the ultrasonographic characteristics of parametrial nodules, prevalence in distinct parametrial areas, and associations with indirect DE signs and concomitant DE nodules. RESULTS: Surgical confirmation of parametrial nodules was observed in 105 of 545 patients (left, 18.5; right, 17.0%). Transvaginal ultrasound demonstrated a sensitivity of 77.1% (95% confidence interval, 68.0%-84.8%) and specificity of 99.1% (95% confidence interval, 67.7%-99.8%). Parametrial nodules typically exhibited characteristics such as a mild hypoechoic appearance (83.6%), starry morphology (74.7%), irregular margins (70.2%), and low vascularization. The posterior parametrial region was the most common location (52.2%), followed by the lateral (41.0%) and anterior (6.8%) parametrial regions. Concomitant DE nodules in the rectum (63.5%) and infiltrating the rectovaginal septum (56.5%) were significantly more prevalent in patients with parametrial involvement. Indirect DE signs, such as the ovaries fixed to the uterine wall (71.8%) and the absence of a posterior sliding sign (51.8%), were also more common in women with parametrial nodules. Hydronephrosis, although relatively uncommon in patients with parametrial involvement (8.2%), was largely detected in lateral parametrial nodules (70.0%). CONCLUSIONS: This study represents a systematic ultrasonographic characterization of parametrial endometriosis. Specifically, it comprehensively assesses the diagnostic accuracy of transvaginal ultrasound in identifying parametrial involvement within a sizable cohort of patients with preoperative suspicion of DE. CLINICAL TRIAL REGISTRATION NUMBER: NCT06017531.

"Things Have Changed"-Laparoscopic Cytoreduction for Advanced and Recurrent Ovarian Cancer: The Experience of a Referral Center on 108 Patients.

OBJECTIVE: To report the feasibility of laparoscopic cytoreduction surgery for primary and recurrent ovarian cancer in a select group of patients. METHODS: A retrospective analysis was conducted on a cohort of patients with FIGO stage IIIA-IV advanced ovarian cancer who underwent laparoscopic primary debulking surgery (PDS), interval debulking surgery (IDS), or secondary debulking surgery (SDS) between June 2008 and January 2020. The primary endpoint was achieving optimal cytoreduction, defined as residual tumor less than 1 cm. Secondary endpoints included evaluating surgical complications and long-term survival, assessed at three-month intervals during the initial two years and then every six months. RESULTS: This study included a total of 108 patients, among whom, 40 underwent PDS, 44 underwent IDS, and 24 underwent SDS. Optimal cytoreduction rates were found to be 95.0%, 97.7%, and 95.8% for the PDS, ISD, and SDS groups, respectively. Early postoperative complications (<30 days from surgery) occurred in 19.2% of cases, with 7.4% of these cases requiring reintervention. One patient died following postoperative respiratory failure. Late postoperative complications (<30 days from surgery) occurred in 9.3% of cases, and they required surgical reintervention only in one case. After laparoscopic optimal cytoreduction with a median follow-up time of 25 months, the overall recurrence rates were 45.7%, 38.5%, and 39.3% for PDS, ISD, and SDS, respectively. The three-year overall survival rates were 84%, 66%, and 63%, respectively, while the three-year disease-free survival rates were 48%, 51%, and 71%, respectively. CONCLUSIONS: Laparoscopic cytoreduction surgery is feasible for advanced ovarian cancer in carefully selected patients, resulting in high rates of optimal cytoreduction, satisfactory peri-operative morbidity, and encouraging survival outcomes. Future studies should focus on establishing standardized selection criteria and conducting well-designed investigations to further refine patient selection and evaluate long-term outcomes.

Ultrasonographic Findings Indirectly Predicting Parametrial Involvement in Patients with Deep Endometriosis: The ULTRA-PARAMETRENDO I Study.

STUDY OBJECTIVE: To evaluate ultrasonographic findings as a first-line imaging tool to indirectly predict the presence of parametrial endometriosis (PE) in women with suspected deep endometriosis (DE) undergoing surgery. DESIGN: Retrospective analysis of a prospectively collected database (ULTRA-PARAMETRENDO I study; NCT05239871). SETTING: Referral center for DE. PATIENTS: Consecutive patients undergoing laparoscopic surgery for DE. INTERVENTIONS: Preoperative transvaginal ultrasonography was done according to the International Deep Endometriosis Analysis consensus statement. A stepwise forward regression analysis was performed considering the simultaneous presence of DE nodules and the following ultrasonographic indirect signs of DE: diffuse adenomyosis, endometriomas, ovary fixed to the lateral pelvic wall or the uterine wall, absence of anterior/posterior sliding sign, and hydronephrosis. The gold standard for the presence of PE was surgery with histologic confirmation. MEASUREMENTS AND MAIN RESULTS: Of 1079 patients, 212 had a surgical diagnosis of PE (left: 18.5%; right: 17.0%; bilateral: 15.9%). The obtained prediction model (χ2 = 222.530; p <.001) for PE included, as independent indirect DE signs presence of hydronephrosis (odds ratio [OR] = 14.5; p = .002), complete absence of posterior sliding sign (OR = 3.3; p <.001), presence of multiple endometriomas per ovary (OR = 3.0; p = .001), and ovary fixation to the uterine wall (OR = 2.4; p <.001); as independent concomitant DE nodules, presence of uterosacral nodules with the largest diameter >10 mm (OR = 3.2; p <.001), presence of rectal endometriosis with the largest diameter >25 mm (OR = 2.3; p = .004), and rectovaginal septum infiltration (OR = 2.3; p = .003). The optimal diagnostic balance was obtained considering at least 2 concomitant DE nodules and at least 1 indirect DE sign (area under the curve 0.75; 95% confidence interval, 0.72-0.79). CONCLUSION: Specific indirect ultrasonographic findings should raise suspicion of PE in women undergoing preoperative assessment for DE. The suspicion of parametrial invasion may be critical to address patients to expert leading centers, where proper diagnosis and surgical treatment for PE can be performed.

Role of ultrasonographic parameters for predicting tubal involvement in infertile patients affected by endometriosis: A retrospective cohort study.

INTRODUCTION: Transvaginal ultrasound is fundamental for the mapping of endometriosis, and the imaging criteria have been clearly described for different organs study. However, no specific ultrasonographic signs of tubal endometriosis have been reported, with the exception of hydrosalpinx, which is the expression of an extreme tubal damage and obstruction. The detection of tubal pathology in infertile patients is fundamental, therefore the aim of the study was to evaluate incidence of tubal endometriosis in infertile patients, and to analyze ultrasonographic signs useful for detection of this condition. MATERIAL AND METHODS: It is a single-center, retrospective cohort study. All 500 consecutive infertile women who underwent laparoscopic surgery for endometriosis were included. The preoperative workup included transvaginal ultrasound and was compared to intraoperative findings and histologic study. RESULTS: The incidence of tubal endometriosis in our study was 8%. Using hydrosalpinx as the ultrasonographic marker for tubal involvement the overall pooled, sensitivity and specificity of TVU were 12% (95%CI, 5-23%) and 99% (95%CI, 98-100%), respectively. If at least one ultrasonographic parameter like hydrosalpinx, periadnexal adhesions or ovarian cyst was considered as a sign of tubal endometriosis, a sensitivity, VPN and specificity were 94% (95% IC, 85-98%), 97% (95%IC, 93-99%) and 31% (95%CI, 27-36%), respectively. DISCUSSION: Hydrosalpinx as ultrasonographic sign alone is characterized by a high specificity but low sensitivity for detection of tubal endometriosis; its sensitivity can be improved by the addition of other markers such as endometrioma and/or periadnexal adhesions.

Inflammation calls for more: Severe pelvic inflammatory disease with or without endometriosis. Outcomes on 311 laparoscopically treated women.

OBJECTIVE: To study possible associations between endometriosis and pelvic inflammatory disease (PID). DESIGN: Retrospective cohort analysis over 14 consecutive years, based on medical records and insurance coding in a tertiary care endometriosis reference center. SETTING: Tertiary care reference center for endometriosis. PATIENTS: Retrospective analysis on all women submitted to laparoscopy in our Unit MAIN OUTCOME MEASURES: Intra-operative data about complications and fertility-impairing procedures, intra-, peri- and post-operative complications. INTERVENTIONS: Retrospective disease codes-triggered chart analysis. RESULTS: The study population was divided into two groups: Group 1 included women with PID and no endometriosis (n = 115); Group 2 included women with PID and endometriosis (n = 96). Endometriosis had a prevalence of 63 % in patients submitted to surgery for PID, significantly higher than the one reported in general population and than the one reported in a Tertiary Care Endometriosis Unit. A significantly higher number of salpingectiomes was needed in group 2 patients (208 versus 80, p < 0.0001). CONCLUSIONS: This study seems to confirm an higher prevalence of pelvic inflammatory disease in endometriosis patients. Intra-operative findings of PID with associated endometriosis show more aggressive patterns.

Are we choosing the correct FSH starting dose during controlled ovarian stimulation for intrauterine insemination cycles? Potential application of a nomogram based on woman's age and markers of ovarian reserve.

PURPOSE: To evaluate the potential application of a nomogram based on woman's age and ovarian reserve markers as a tool to optimize the follicle-stimulating hormone (FSH) starting dose in intrauterine insemination (IUI) cycles. METHODS: We conducted a retrospective analysis enrolling 179 infertile women undergoing controlled ovarian stimulation (COS), followed by IUI. Each woman received an FSH starting dose according to clinical decision. After collecting data about COS and IUI procedures, we calculated the FSH starting dose according to the nomogram. The main outcomes measured were women's baseline characteristics, COS, and clinical outcomes. RESULTS: The FSH starting dose calculated by the nomogram was significantly lower than the one actually prescribed (p < 0.001), in only 14.8% of the cycles nomogram calculated a higher starting dose. When gonadotropin dose was decreased during COS, and similarly in case of hyper-response (more than two follicles ≥ 16 mm retrieved), the FSH starting dose calculated by the nomogram would have been lower in most of the cases (81.8% and 48.8%, respectively). Conversely, when gonadotropin dose was increased during COS and in case of low ovarian response (no follicle ≥ 16 mm retrieved), the FSH starting dose calculated by the nomogram would have been lower in most of the cases (64.7% and 100%, respectively); in these groups median anti-Müllerian hormone (AMH) level was 5.62 ng/mL. CONCLUSIONS: The application of this nomogram in IUI cycles would lead to a more tailored FSH starting dose and improved cost-effectiveness, although in PCOS women, particularly the ones with high AMH, it does not seem adequate.

Inositol phosphoglycans and preeclampsia: from bench to bedside.

The metabolic syndrome that occurs in preeclampsia reflects the complex interactions between immunological alterations and the systemic inflammation that have been shown to take place during this complication of human pregnancy. Inositol phosphoglycans play a definite role in the insulin resistance in preeclampsia with a higher production and urinary excretion of this molecule before and during preeclampsia. Recent researches suggest that the feto-placental glucose metabolism in the first and early second trimester is mainly linked to the nonoxidative pathway of glycogen catabolism supporting the pivotal role of the inositol phosphoglycan P-type. In this article we present the results of a case-control study carried out in the first trimester to evaluate the potential of urinary P-IPG release as a early marker of the disease. A single mid-stream sample of maternal urine was collected at 11 weeks of gestation for this single centre retrospective study. Twenty-seven patients out of 331 women recruited (8.1%) went on to develop preeclampsia but no sample attained positivity. Further details about the development of the metabolic syndrome during preeclampsia were retrieved also from other studies to implement our knowledge about the pathophysiology of this syndrome and to identify biochemical aspects that could help in clinical practice.