Anterior compartment endometriosis

Anterior compartment pelvic endometriosis consists in  the presence of endometrium-like tissue and stroma lesion  s localized in the anterior pelvic structures; when extending under the peritoneal surface, these lesions are considered nodules of deep endometriosis (DE) [1]. 

The most important localizations  of anterior compartment DE are bladder endometriosis (BE) and pre-vesical   ureteral endometriosis (UE), both part  of urinary tract endometriosis (UTE).
BE is defined as the presence of endometrium-like tissue  and stroma  in the detrusor muscle [2]; UE is diagnosed when endometrium-like  tissue and stroma  are localized in ureteral wall [3]. DE nodules infiltrating the anterior parametrium (corresponding to the connective tissue surrounding both ureters) and the vesicouterine pouch should be considered part of anterior compartment endometriosis, although a standardized description of these two localizations has been not yet reported. 

GA10 Endometriosis
GA10.D Endometriosis of urinary system  
GA10.D0 Endometriosis of the bladder  
GA10.DY Endometriosis of other sites in the urinary system  
GA10.DZ Endometriosis of unspecified site in the urinary system  
GA10.Y Endometriosis of other specified sites  

The prevalence  of UTE ranges from 1 to 6% of all individuals  affected by endometriosis [4], occurring more frequently in patients with DE (15-55%) [4, 5]. The urinary bladder is the most frequent organ involved (70-85% of cases) [6]. The prevalence of UE varies considerably from 0.01% to 1.7% in individuals with endometriosis [7, 8]. 
BE most frequently involves the vesical base and dome. UE is commonly unilateral, with a left-sided predisposition, often affecting the distal third ureteral segment at about 3-4 cm above the vesicoureteral junction [3]. 
In patients undergoing surgery for DE, parametrial involvement may be a common finding, present in 15-75% of cases (9-11). Although the exact prevalence of parametrial endometriosis has been estimated with varying results, the specific incidence of anterior parametrial endometriosis has not been established.

Similar to other DE locations, the pathogenesis of anterior compartment endometriosis remains unclear. The retrograde menstruation theory and the Müllerian remnant theory are among the hypothesis of debate for sustaining  endometriosis development [9]. 
Some authors suggest that BE may occur following the implantation of endometrial cells on the peritoneum of the anterior pouch. Alternately,  UE may originate from implantation of these cells on the lateral pelvis,  therefore, the two forms are not frequently associated [6]. The positional predisposition of UE to the left lateral and distal third lower ureteral segment supports the hypothesis of retrograde menstruation [7]. Consistent with this theory, decreased fluid movement in the left hemipelvis due to the presence of the sigmoid colon would favor adhesion and growth of menstrual endometrium regurgitated by tubes on the peritoneal surface of the left pelvic sidewall. The retrograde menstruation theory could also explain the origin of anterior parametrial and subperitoneal vesicouterine pouch nodules, which may be the result of the infiltration of superficial peritoneal implants.
The Müllerian-remnant theory hypothesizes that DE originated from adenomyosis localized in the retroperitoneum secondary to embryonic rests of the Müllerian duct or as an extension of adenomyotic nodules arising in the myometrium. DE implants [10], including those affecting ureters and bladder [11], are histologically characterized by fibrotic and smooth myomatous tissue with islands or strains of glands and stroma, similarly  to uterine adenomyosis; this  adds support to the Müllerian-remnant theory. Therefore, the concept of “adenomyotic disease of the retroperitoneal space” was introduced. According to this theory, anterior invasion of vesicovaginal space by adenomyotic nodules may be implicated in the genesis of BE and lateral invasion through parametrium in pre-vesical UE (where the ureter proceeds toward the parametrial tunnel) [11]. Other authors hypothesize that the hematogenic or lymphatic spread of endometrial cells may be responsible for the genesis and establishment of distant implants [12].

For all endometriotic implants, histopathology remains the definitive modality of diagnosis. BE is defined as the presence of endometrial-like glands and stroma in vesical detrusor muscle [2]. 
Ureteral endometriosis is frequently classified as extrinsic or intrinsic according to histologic characteristics: in the extrinsic pattern, endometriosis invades the ureteral adventitia extending from the surrounding connective ureteral tissue (belonging to parametrium), and hence is potentially able to cause extrinsic compression of the ureteral wall; in the intrinsic disease, endometriosis tissue directly infiltrates the muscularis, submucosa, or mucosa of the ureter. These two types of UE may coexist along the ureteral course [13]. Severe ureteral obstruction has been reported to be even more seen commonly with extrinsic UE [14], as it is often related to secondary fibrosis originating near the endometriotic implants.

UE is often associated with wide parametrial involvement arising from a persistent DE affecting the posterior parametrium (uterosacral ligaments, rectovaginal ligaments   , lateral rectal ligaments) and lateral parametrium (cardinal ligaments, vesicouterine ligaments) [15]. UE nodules might result from the extension of large endometriotic nodules localized in rectovaginal space (47-56% of cases), uterosacral ligaments (10-50%), and bowel (26-39%) [16-18]. Isolated UE is rare [18]. 

Symptoms and Signs
Documented symptoms of dysmenorrhea, dyspareunia, and non-menstrual pelvic pain in individuals of reproductive age should raise the suspicion of DE [19].
Up to 50% of patients with UE may not have specific symptoms; these patients may  complain of flank or abdominal pain, and/or gross hematuria [3]. Conversely, patients with BE (approximately 70%) may  present with urinary symptoms, such as dysuria, frequency, and bladder pain; less commonly, hematuria and urinary urgency may be described  [2]. 
Physical examination allows identification of a palpable nodule or a thickened area along the anterior vaginal wall that may be painful in 35–100% of patients with BE [2]. In contrast. physical examination is not usually abnormal in UE , although the palpation of a posterior compartment nodule or a wide parametrial retraction may suggest an eventual ureteral involvement. 
The degree of symptoms correlates poorly with the degree of ureteral obstruction due to UE [3].

Ultrasound
Ultrasonography has a fundamental role in diagnosing and planning the most appropriate treatment for anterior compartment endometriosis. 
Obliteration of the uterovesical region, which can be related to anterior compartment DE, can  be evaluated by the anterior sliding sign [20]. This is evaluated by placing the transvaginal probe in the anterior fornix and, therefore, balloting the uterus between the probe and one hand of the operator placed over the suprapubic region. A vesicouterine septum is considered non-obliterated if the posterior vesical wall slides freely over the anterior uterine wall (sliding sign positive); otherwise, a vesicouterine septum is considered obliterated if the posterior vesical wall does not slide freely over the anterior uterine wall (sliding sign negative). Although the anterior sliding sign has been reported in the International Deep Endometriosis Analysis (IDEA) criteria for evaluating patients with suspected endometriosis, it has been not validated in the current literature [20].
In suspected BE, location, size, and distance of the nodule from ureteral orifices should be evaluated. On ultrasound, BE nodules are generally spherical or comma-shaped lesions with regular or irregular margins; they are usually covered by a small hyperechoic rim reflecting layers of the bladder wall (submucosal and serosa). Their Colour Doppler analysis reveals minimal to moderate internal blood flow and this may help in doing a differential diagnosis between other bladder intraluminal lesions [21]. According to IDEA criteria, BE should be localized to the following bladder zones: base, dome, trigone, and extra-abdominal areas. The BE nodules should be measured in three orthogonal planes [20]. The addition of three-dimensional (3D) reconstruction does not improve the performance of transvaginal ultrasound in diagnosing the presence and characteristics of BE [22]. 
Ultrasound may allow for visualization of anterior parametrial nodules, which can eventually cause an extrinsic ureteral involvement. These nodules are described as hypoechoic areas with irregular margins, low vascularization, starry morphology, and close to paracervical tissue on transverse plane [23]. 
In the case of concomitant anterior parametrial nodules or large trigonal BE nodules (which may infiltrate the vesical intramural ureter [2]), the pre-vesical ureter may undergo dilatation (hydroureter), appearing as a tubular anechoic structure with or without vermiculation (contractions to move urine from kidneys to bladder), similarly to blood vessels but with negative vascular activity on Color and Power doppler analysis.
In general, the location and distance between the ureteral stricture and the bladder should be estimated, evaluating the ureteral diameters before and after the point of stenosis [3]. Although it has not been systematically reported, TVS allows for detecting (sub)mucosal infiltration of BE nodules [24]. 
Currently, a standardized and reproducible exploratory technique for evaluating DE parametrial lesions and establishing a common terminology for describing the anatomy at imaging and surgery has not been reported. In the case of UE, abdominal ultrasonography may demonstrate hydronephrosis, which should be graded on the appearance of the calyces and renal pelvis, and on the thickness of the renal parenchyma. 

Patients with BE and UE may present urinary symptoms similar to those caused by urinary tract infections and urinary tract stones. The ultrasonographic evaluation and urine culture have an important role in differentiating urinary tract endometriosis and these  two other clinical conditions. In addition, the presence of urinary tract stones can be identified at ultrasound as mobile and echogenic formations with associated acoustic shadowing. Additionally, bladder wall thickening due to inflammation, can be visualized at ultrasound, being associated to chronic urinary tract infections and the presence of urinary tract stones. Abdominal X-ray and computed tomography (CT) can be employed to detect the presence of most urinary tract stones [5].
Another differential diagnosis is bladder papilloma, which can be diagnosed by guided tissue sampling at cystoscopy. Differentiating BE from bladder cancer, which can have overlapping symptoms, may be challenging. At the ultrasound, BE nodules are often distinguished by a small hyperechogenic rim reflecting layers of the bladder wall (submucosal and serosa).  In contrast, in bladder cancers, spiky, or papillary projections interrupt the hyperechogenic layers of the bladder wall. Additionally, cancerous bladder lesions may show significant intralesional vascularity at Color Doppler analysis. 
BE should also be distinguished from interstitial cystitis, a diagnosis of exclusion after eliminating the presence of other conditions [25].
UE should be also differentiated from other urologic causes of intrinsic or extrinsic ureteral stenosis, such as primary or metastatic cancer and idiopathic retroperitoneal fibrosis. These conditions primarily affect postmenopausal individuals in most cases [3, 25]. 

In the last years, ultrasound has been increasingly employed for detecting the presence of endometriosis as the first diagnostic tool [20]. Magnetic resonance imaging (MRI) should be considered as a complementary or supplementary imaging technique to ultrasound in the presurgical staging of anterior compartment endometriosis, particularly, in patients with no conclusive ultrasonographic findings. The use of cystoscopy is not routinely advised, but only in cases where malignancy is suspected or to estimate the distance between BE nodules and ureteral orifices if not evaluable at ultrasound [2]. Retrograde ureteropyelography may be used for intraoperatively localizing the level and degree of obstruction due to UE. Pre-operative renal scintigraphy may be considered whenever hydronephrosis or hydroureter is present to estimate glomerular filtration rate and to help to predict the efficacy of surgical decompression of ureteral obstruction in ameliorating kidney function [3].

When evaluating patients with suspected endometriosis, the routine ultrasonographic examination should be extended beyond the uterus and ovaries into the anterior pelvic compartments to evaluate structural mobility and to look for DE nodules [26]. Patients suffering from symptoms suggestive of DE, including anterior compartment endometriosis. can benefit from a preoperative sonographic diagnosis performed by experienced ultrasonographers having received dedicated training for endometriosis.  The International Deep Endometriosis Analysis (IDEA) criteria should be employed for characterizing the presence of endometriosis [20]. 

Medical treatment
Hormonal treatment should be considered an effective option for patients with DE, including anterior compartment endometriosis. The choice of the optimal medical compound is based on patient preferences and treatment goals as well as the efficacy and the safety profile, the desire for contraception, the cost, and the route of administration of the drugs. In the majority of cases, combined contraceptives and progestogens are employed as first-line hormonal for patients with DE [27]. 
Medical therapy has been reported efficacious for treating symptoms related to BE [2]. Hence, if the decision is taken to medically control BE, thus avoiding excisional surgery, long-term treatment should be planned. Medical therapy is contraindicated as a first-line treatment in patients with ureteral obstruction because of the risk of progressive increase in the severity of ureteral stenosis and hydronephrosis which could lead to loss of renal function. However, the role of hormonal therapy in patients with UE without obstruction and suffering pain symptoms has not been established. In these patients, hormonal drugs can be employed for controlling symptoms or while planning the surgical approach under renal function control [3].  

Surgical treatment
Surgical treatment of BE should be performed after an accurate diagnostic workup. Two techniques for surgical treatment of BE have been proposed: transurethral resection (TUR) and partial cystectomy (alone or in combination). TUR has been reported for treating BE nodules even though evidence supporting the efficacy and safety of this procedure is poor. Partial cystectomy consists of partial bladder resection for detrusor endometriosis with or without preventive cystoscopic catheterization of the ureters. In general, the main objective of each surgical procedure should be to entirely remove the bladder lesion [2, 28].
The surgical treatment of UE aims to relieve ureteral obstruction and avoid recurrence. The presence of hydroureteronephrosis should be a strong indication for surgical treatment, which includes conservative ureterolysis or radical approaches, such as ureterectomy, with end-to-end anastomosis, ureteroneocystostomy, and/or nephroureterectomy [29]. The surgical treatment depends on the extension of ureteral nodules and renal function. In current experience, ureterolysis and eventual nerve-sparing parametrectomy with resection of involved ligaments is an optimal surgical option [30]. After that, a definitive decision concerning ureteroneocystostomy is considered after a meticulous evaluation of the ureteral course, caliber, presence of vermiculation, and residual vascularization. More than 50% of the patients may reveal extrinsic endometriosis on histopathologic specimens but will require ureteroneocystostomy after extensive ureterolysis [31]. Additionally, distal ureteral resection with ureteral reimplantation and bladder psoas hitch (if necessary) should be considered when the nodules involve the bladder trigone [28]. In patients with suspected UE, preoperative ureteral stenting may facilitate ureteral identification and guide ureterolysis; postoperative ureteral stenting may help to prevent its obstruction caused by local edema and inflammation after surgery, which may be responsible for complications (i.e., ureteral fistula) [3]. 

The risk of anterior compartment endometriosis recurrence after surgical treatment has not been reported in the current literature. In general, for the prevention of recurrence of DE and associated symptoms, long-term administration of postoperative hormone suppression/treatment  (estroprogestins, progestins, and GnRH-agonists) should be considered [32]. 

Anterior compartment DE is a challenging condition. In particular, UE may be asymptomatic or associated with non-specific disease symptoms, which, if not correctly diagnosed, can lead to persistent hydronephrosis and ultimately renal failure. Therefore, prompt detection and treatment of this condition are mandatory. The possible coexistence of other locations of DE (such as posterior compartment endometriosis) adds support to the fact that clinical management should be undertaken at specialized centres comprised of dedicated sonographers and advanced gynecological surgeons working in multidisciplinary collaboration with urologists and general surgeons. 

1.    International working group of AAGL, et al., An International Terminology for Endometriosis, 2021. J Minim Invasive Gynecol, 2021. 28(11): p. 1849-1859.
2.    Leone Roberti Maggiore, U., et al., Bladder Endometriosis: A Systematic Review of Pathogenesis, Diagnosis, Treatment, Impact on Fertility, and Risk of Malignant Transformation. Eur Urol, 2017. 71(5): p. 790-807.
3.    Barra, F., et al., Ureteral endometriosis: a systematic review of epidemiology, pathogenesis, diagnosis, treatment, risk of malignant transformation and fertility. Human Reproduction Update, 2018: p. dmy027-dmy027.
4.    Knabben, L., et al., Urinary tract endometriosis in patients with deep infiltrating endometriosis: prevalence, symptoms, management, and proposal for a new clinical classification. Fertil Steril, 2015. 103(1): p. 147-52.
5.    Gabriel, B., et al., Prevalence and management of urinary tract endometriosis: a clinical case series. Urology, 2011. 78(6): p. 1269-74.
6.    Berlanda, N., et al., Ureteral and vesical endometriosis. Two different clinical entities sharing the same pathogenesis. Obstet Gynecol Surv, 2009. 64(12): p. 830-42.
7.    Vercellini, P., et al., Is ureteral endometriosis an asymmetric disease? BJOG, 2000. 107(4): p. 559-61.
8.    Antonelli, A., et al., Clinical aspects and surgical treatment of urinary tract endometriosis: our experience with 31 cases. Eur Urol, 2006. 49(6): p. 1093-7; discussion 1097-8.
9.    Vercellini, P., et al., Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol, 2014. 10(5): p. 261-75.
10.    Anaf, V., et al., Smooth muscles are frequent components of endometriotic lesions. Hum Reprod, 2000. 15(4): p. 767-71.
11.    Donnez, J., M. Nisolle, and J. Squifflet, Ureteral endometriosis: a complication of rectovaginal endometriotic (adenomyotic) nodules. Fertil Steril, 2002. 77(1): p. 32-7.
12.    Fujita, K., Endometriosis of the ureter. J Urol, 1976. 116(5): p. 664.
13.    Yohannes, P., Ureteral endometriosis. J Urol, 2003. 170(1): p. 20-5.
14.    Frenna, V., et al., Laparoscopic management of ureteral endometriosis: our experience. J Minim Invasive Gynecol, 2007. 14(2): p. 169-71.
15.    Ceccaroni, M., et al., Total Laparoscopic Ureteroneocystostomy for Ureteral Endometriosis: A Single-Center Experience of 160 Consecutive Patients. J Minim Invasive Gynecol, 2018.
16.    Seracchioli, R., et al., Histological evaluation of ureteral involvement in women with deep infiltrating endometriosis: analysis of a large series. Hum Reprod, 2015. 30(4): p. 833-9.
17.    Bosev, D., et al., Laparoscopic management of ureteral endometriosis: the Stanford University hospital experience with 96 consecutive cases. J Urol, 2009. 182(6): p. 2748-52.
18.    Uccella, S., et al., Laparoscopy for ureteral endometriosis: surgical details, long-term follow-up, and fertility outcomes. Fertil Steril, 2014. 102(1): p. 160-166 e2.
19.    Koninckx, P.R., et al., Deep endometriosis: definition, diagnosis, and treatment. Fertil Steril, 2012. 98(3): p. 564-71.
20.    Guerriero, S., et al., Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group. Ultrasound Obstet Gynecol, 2016. 48(3): p. 318-32.
21.    Guerriero, S., et al., Accuracy of transvaginal ultrasound for diagnosis of deep endometriosis in uterosacral ligaments, rectovaginal septum, vagina and bladder: systematic review and meta-analysis. Ultrasound Obstet Gynecol, 2015. 46(5): p. 534-45.
22.    Barra, F., et al., Ultrasonographic 3D Evaluation in the Diagnosis of Bladder Endometriosis: A Prospective Comparative Diagnostic Accuracy Study. Gynecol Obstet Invest, 2021. 86(3): p. 299-306.
23.    Mariani, L.L., et al., Sonographic features of endometriosis infiltrating the lateral parametrium. J Gynecol Obstet Hum Reprod, 2021. 50(7): p. 102-116.
24.    Ros, C., et al., Accuracy of Transvaginal Ultrasound Compared to Cystoscopy in the Diagnosis of Bladder Endometriosis Nodules. J Ultrasound Med, 2020.
25.    Scioscia, M., et al., Ultrasound Differential Diagnosis in Deep Infiltrating Endometriosis of the Urinary Tract. J Ultrasound Med, 2020. 39(11): p. 2261-2275.
26.    Leonardi, M. and G. Condous, How to perform an ultrasound to diagnose endometriosis. Australas J Ultrasound Med, 2018. 21(2): p. 61-69.
27.    Ferrero, S., F. Barra, and U. Leone Roberti Maggiore, Current and Emerging Therapeutics for the Management of Endometriosis. Drugs, 2018. 78(10): p. 995-1012.
28.    Ceccaroni, M., et al., Total laparoscopic bladder resection in the management of deep endometriosis: "take it or leave it." Radicality versus persistence. Int Urogynecol J, 2020. 31(8): p. 1683-1690.
29.    Cavaco-Gomes, J., et al., Laparoscopic management of ureteral endometriosis: A systematic review. Eur J Obstet Gynecol Reprod Biol, 2017. 210: p. 94-101.
30.    Ceccaroni, M., R. Clarizia, and G. Roviglione, Nerve-sparing Surgery for Deep Infiltrating Endometriosis: Laparoscopic Eradication of Deep Infiltrating Endometriosis with Rectal and Parametrial Resection According to the Negrar Method. J Minim Invasive Gynecol, 2020. 27(2): p. 263-264.
31.    Ceccaroni, M., et al., Total Laparoscopic Ureteroneocystostomy for Ureteral Endometriosis: A Single-Center Experience of 160 Consecutive Patients. J Minim Invasive Gynecol, 2019. 26(1): p. 78-86.
32.    Members of the Endometriosis Guideline Core, G., et al., ESHRE guideline: endometriosis. Hum Reprod Open, 2022. 2022(2): p. hoac009.

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