Clinical Research Directory

Deep Endometriosis Affecting the Urogenital Tract: Long-term Outcomes and Impact on Renal Function

Endometriosis is a chronic estrogen-dependent disease characterized by the presence and growth of endometrium-like tissue outside the uterine cavity. This ectopic endometrial tissue induces a chronic local and systemic inflammatory response, resulting in the most common manifestations of the disease: chronic pelvic pain, infertility, and pelvic adhesions. In deep endometriosis (DE), adhesions and infiltrative growth may damage adjacent organs. Overall, endometriosis affects approximately 10% of women of reproductive age. Its prevalence is higher among women with infertility (20-50%) and among patients with chronic pelvic pain (up to 90%). The disease is usually categorized as superficial peritoneal, ovarian, or deep endometriosis (DE). Deep endometriosis is a progressive form of the disease that may affect organs beyond the pelvic cavity, including the urinary tract, alter their anatomy, and cause functional impairment. Urogenital involvement occurs in approximately 1-5.5% of all women with endometriosis; the prevalence is substantially higher among patients with DE, reaching 16-53% according to the available literature. Within the urinary tract, the bladder is most commonly affected (70-85%), followed by the ureters (9-23%), kidneys (approximately 4%), and urethra (approximately 2%). Ureteral endometriosis is therefore a relatively rare but clinically significant entity. It may be unilateral or bilateral, with a predominance of left-sided involvement. Two basic forms are distinguished: * "Extrinsic" - ureteral stenosis caused by periureteral fibrosis and the presence of DE lesions without infiltration of the ureteral wall. * "Intrinsic" - ureteral stenosis caused by direct infiltration of the ureteral wall by endometriotic tissue. Ureteral stenosis causes secondary hydronephrosis and, unless treated in a timely manner, may lead to a progressive loss of renal function. The disease frequently remains asymptomatic for a prolonged period. Up to half of cases are diagnosed incidentally or only at an advanced stage, when renal damage is already irreversible. Early detection and timely planning of surgical management are therefore essential for preserving renal function. The main surgical procedures are: * ureterolysis - release of the ureter from fibrotic adhesions, preferred for the extrinsic form; * ureteroneocystostomy (UCNA) - indicated for the intrinsic form when the affected segment must be resected and the ureter reimplanted into the bladder; * ureteroureterostomy (ureteral anastomosis) - appropriate for the intrinsic form when, following resection, the distal ureteral segment is sufficiently long to allow anastomosis of healthy margins. Despite the clinical significance of the condition, prospective studies objectively evaluating the evolution of renal function after the individual types of surgical management of ureteral endometriosis are still lacking. A modern diagnostic strategy combining specialized ultrasound, dynamic renal scintigraphy (MAG3), and analysis of urinary biomarkers of tubular injury (KIM-1, CCL-2, L-FABP) enables earlier detection of renal dysfunction and more accurate monitoring of postoperative recovery. Identification of sensitive biomarkers of early renal injury and validation of an algorithm for their use could substantially improve decisions regarding the timing of surgery and subsequent postoperative follow-up. Based on our experience, some patients surgically treated for hydronephrosis caused by DE-related ureteral stenosis show persistent morphological changes on renal ultrasound and the manifestation of systemic conditions such as arterial hypertension during long-term follow-up. To date, no study has focused on the long-term follow-up of patients with ureteral DE and its potential consequences. The expected benefit of this study is to establish clear criteria for the indication of surgical treatment of ureteral endometriosis and to develop an evidence-based protocol for long-term follow-up.

Combining Ultrasound and Biomarkers to Diagnose Superficial Endometriosis

Endometriosis is a benign gynecological disease characterized by uterine-like cells growing outside the uterus, leading to pain, infertility, and inflammation. Endometriosis most commonly occurs in the forms of Superficial Endometriosis (SE), Deep Endometriosis and Ovarian Endometriosis (Endometrioma) (OE). Ultrasound diagnosis of DE and OE has become more reliable with advances in ultrasound technology, technique and expertise, leading to decreased diagnosis time for patients and allowing for better optimization of surgeries if required. SE, however, lacks any reliable non-invasive diagnosis methods. SE is the most common form of endometriosis and is defined as a disease that lines the peritoneum and is small and superficial in nature, leading to chronic inflammation, infertility, and pain. SE is difficult to visualize on ultrasound due to its size and alignment with tissue, requiring fluid to expand the pelvis and partially suspend these small lesions, allowing them to be diagnosed through ultrasound. Leonardi et al. observed that in some patients, a physiologic change occurs whereby fluid fills the pouch of Douglas (POD), allowing increased visualizing during ultrasound. This led to the development of Saline-infused sonoPODgraphy (SPG), a novel method utilizing modified commonly used ultrasound techniques called saline-infusion sonohysterography (SIS) and hysterosalpingo-contrast-sonography (HyCoSy), to reliably visualize the POD (Leonardi et al, 2019). Visualizing the POD is important as SE is often deposited in the POD. This diagnostic accuracy pilot study aims to pioneer the technique whereby SPG will be evaluated as a novel, rapid, non-invasive diagnostic tool for SE. The injected fluid from the POD will be withdrawn and evaluated for novel biomarkers, allowing us to further develop rapid diagnostics and better understand disease mechanisms. We hypothesize that SPG will allow for the diagnosis of SE with a diagnostic accuracy parallel to the current invasive gold standard, laparoscopy.

Impact of Food Supplementation on Quality of Life in Patients With Endometriosis and Pelvic Pain.

This study examines whether the food supplement Doliral can improve quality of life and reduce pelvic pain in women with endometriosis, compared with placebo, over several weeks.

Observational Study on the Use of Ultrasound to Recognize Superficial Endometriosis in a Specific Area of the Pelvis (the Uterosacral Ligaments)

An observational, prospective, multicenter study conducted on patients of childbearing age undergoing laparoscopic surgery for early-stage benign or malignant gynecological disease. The study does not include changes to the standard care pathway.

Assessing the Efficacy of Indocyanine Green for Ureter Identification During Robot-Assisted Surgery in Advanced-Stage Endometriosis

The goal of this side-randomized, self-controlled trial, 1-site study is to explore the efficacy of Indocyanine Green Fluorescence (ICG) for Intraoperative Ureter Identification During Robot-Assisted Single-Site Surgery in Advanced-Stage Endometriosis. Researchers will perform temporary ureteral stent using indocyanine green fluorescence for intraoperative ureteral identification on either the left or right side of subjects who are undergoing a robotic assisted transumbilical resection of advanced endometriosis. Participants will be randomized to receive ICG-assisted ureteral identification on either the left or right side. Randomization will be conducted using a computer-generated block randomization method. The primary aim is to determine whether ICG-assisted ureter visualization can reduce operative time for endometriosis resection and ureterolysis, and minimize the risk of ureteral injury. Secondary objectives are to assess the feasibility and safety of temporary ureteral ICG stenting for intraoperative ureter identification in advanced endometriosis.