"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.

Experimental and new investigational drugs for the treatment of uterine fibroids.

INTRODUCTION: Uterine fibroids, the most prevalent benign tumors among reproductive-age women, pose treatment challenges that range from surgical interventions to medical therapies for symptom control. Progestins and estroprogestins effectively manage uterine bleeding by suppressing dysfunctional endometrium over fibroids. While GnRH agonists represent a crucial milestone in symptom treatment, their prolonged use results in menopausal-like symptoms and irreversible bone mineral density loss. Advancements in understanding fibroid pathophysiology have prompted the exploration of new compounds to overcome current therapy limitations. AREAS COVERED: This manuscript offers an updated overview of investigational drugs for symptomatic uterine fibroids. EXPERT OPINION: Despite ulipristal acetate's well-established efficacy as a selective progesterone receptor modulator (SPRM) in fibroid treatment, its prescription has declined due to the rare but severe risk of liver damage. Oral GnRH antagonists, like elagolix, relugolix, and linzagolix, with their novel pharmacodynamic properties, are gaining traction in fibroid management, inducing a dose-dependent reduction in circulating sex hormone levels. Ongoing research on natural compounds, such as vitamin D and epigallocatechin gallate (EGCG), presents emerging options for treating uterine fibroids. This evolving landscape reflects the ongoing efforts to improve therapeutic outcomes for individuals with symptomatic uterine fibroids.

A review of phase II and III drugs for the treatment and management of endometriosis.

INTRODUCTION: Endometriosis is an estrogen-dependent disease that gives rise to pelvic pain and infertility. Although estroprogestins and progestins currently stand as the first-line treatments for this condition, demonstrating efficacy in two-thirds of patients, a significant portion of individuals experience only partial relief or symptom recurrence following the cessation of these therapies. The coexistence of superficial, deep endometriosis, and ovarian endometriomas, as three distinct phenotypes with unique pathogenetic and molecular characteristics, may elucidate the current heterogeneous biological response to available therapy. AREAS COVERED: The objective of this review is to furnish the reader with a comprehensive summary pertaining to phase II-III hormonal treatments for endometriosis. EXPERT OPINION: Ongoing research endeavors are directed toward the development of novel hormonal options for this benign yet debilitating disease. Among them, oral GnRH antagonists emerge as a noteworthy option, furnishing rapid therapeutic onset without an initial flare-up; these drugs facilitate partial or complete estrogen suppression, and promote prompt ovarian function recovery upon discontinuation, effectively surmounting the limitations associated with previously employed GnRH agonists. Limited evidence supports the use of selective estrogen and progesterone receptor modulators. Consequently, further extensive clinical research is imperative to garner a more profound understanding of innovative targets for novel hormonal options.

Rituximab for endometriosis: Unlikely translatability from oncology due to safety concerns?

This letter discusses the article "The Effects of Rituximab on Experimental Endometriosis Model in Rats" by Dogan et al., which evaluated the potential therapeutic efficacy of rituximab in an experimental animal model of endometriosis. While the study showed promising results in decreasing the volume of endometriotic implants and differences in B-cell count and fibrosis score, rituximab is typically used as a therapy for B lymphocyte malignancies and has potential short-term and long-term side effects. Additionally, animal models for endometriosis have limitations, and novel models are still being developed. Therefore, further preclinical research is necessary to evaluate the safety and efficacy of rituximab as a potential treatment for endometriosis in humans.

Incidence and ultrasonographic characteristics of cesarean scar niches after uterine closure by double-layer barbed suture: A prospective comparative study.

OBJECTIVE: To compare the ultrasonographic features of uterine scars and clinical symptoms after cesarean delivery (CD) using barbed and conventional smooth sutures. METHODS: This case-control study enrolled women who underwent primary CD at 37 weeks of pregnancy or later. The uterus was closed using either double-layer unidirectional barbed suture or conventional double-layer smooth suture. Ultrasound scans of the uterine scar and evaluations of menstrual patterns were performed at 6, 12, and 24 months after surgery. RESULTS: In all, 102 patients underwent uterine closure with barbed suture, while 135 patients underwent smooth suture. At 6 months, patients in the barbed group had a lower incidence of uterine niches (20.2% vs 32.6%) that were also shallower in depth (P < 0.001). Lower incidence of niches was also observed in the barbed group at 12 and 24 months (P = 0.043 and 0.048, respectively). At these two follow-up times, the smooth group had a higher number of patients reporting postmenstrual spotting (P < 0.05) and more postmenstrual spotting days per month (P < 0.050). CONCLUSION: The use of double-layer barbed suture during CD was associated with a lower incidence of scar niches and a more favorable menstrual pattern compared with the use of smooth suture.

Comparing the pharmacokinetic and pharmacodynamic qualities of current and future therapies for uterine fibroids.

INTRODUCTION: Uterine fibroids are the most common benign gynecological tumors affecting women of reproductive ages. Although surgery is the definitive treatment choice, several medical approaches have been investigated to control their symptoms. The main issue of currently employed drugs for uterine fibroids is the long-term safety and tolerability profile. Today, new emerging options represent hopeful alternatives that could potentially overcome these limitations. AREAS COVERED: This manuscript aims to give an updated overview of the pharmacodynamic and pharmacokinetic properties of current and new investigational medical drugs for the treatment of symptomatic uterine fibroids. The bibliographic research was conducted by searching alone or combined keywords on the following electronic databases: Medline, PubMed, Embase, Science Citation Index via Web of Science. EXPERT OPINION: The most recent therapeutic strategies for uterine fibroids are represented by gonadotropin-releasing hormone antagonists (GnRH-ants; elagolix and relugolix) and selective progesterone receptor modulators (SPRM; ulipristal acetate). After early promising results, studies on innovative drugs, such as linzagolix (GnRH-ant) and vilaprisan (SPRM) are demanding. In the near future, a deeper knowledge of biological mechanisms at the basis of the genesis and growth of uterine fibroids could pave the way for the development of innovative targeted therapies.