There is a major difference between the clinical presentations of endometriosis causing intestinal stenosis and endometriosis causing ureteral stenosis. Whereas a severe bowel stricture originating from endometriosis infiltration, by definition, gives rise to subocclusive symptoms, obstructive uropathy because of ureteral endometriosis may go unnoticed and cause progressive hydroureteronephrosis in the absence of colicky pain (1Nezhat C. Falik R. McKinney S. King L.P. Pathophysiology and management of urinary tract endometriosis., 2Barra F. Scala C. Biscaldi E. Vellone V.G. Ceccaroni M. Terrone C. et al.Ureteral endometriosis: a systematic review of epidemiology, pathogenesis, diagnosis, treatment, risk of malignant transformation and fertility.).Women with a diagnosis of deep endometriosis, which is the lesion phenotype most frequently associated with ureteral involvement, should systematically undergo an ultrasound evaluation of the urinary tract to rule out ureteral dilatation. Reduced or absent kidney function can be detected with elusive or no previous suggestive symptoms, although this occurs infrequently (1Nezhat C. Falik R. McKinney S. King L.P. Pathophysiology and management of urinary tract endometriosis., 2Barra F. Scala C. Biscaldi E. Vellone V.G. Ceccaroni M. Terrone C. et al.Ureteral endometriosis: a systematic review of epidemiology, pathogenesis, diagnosis, treatment, risk of malignant transformation and fertility.). With awareness of this potential condition, ultrasonographic screening and active surveillance of all women with deep endometriotic lesions may limit the risk of this severe disease complication.Arena et al. (3Arena A. Del Forno S. Orsini B. Iodice R. Degli Esposti E. Aru A.C. et al.Ureteral endometriosis, the hidden enemy: multivariable fractional polynomial approach for evaluation of pre-operative risk factors in the absence of ureteral dilatation.) have tried to take a further step forward, that is, to predict ureteral involvement in the form of extrinsic compression or distortion caused by endometriosis even in the absence of stenosis and secondary ureteral dilatation. Toward this aim, they prospectively assessed a series of women with a diagnosis of deep endometriosis of the posterior compartment who were scheduled for excisional surgery. In addition to detailed clinical evaluation, including the use of validated scales for measuring the severity of symptoms, the patients systematically underwent transvaginal and transabdominal ultrasonography. According to the investigators, “the diagnosis of ureteral involvement required the retroperitoneal isolation and examination of the diameter, course, and consistency of both ureters in the pelvis.” During a 40-month period, 300 consecutive patients underwent surgery for posterior deep infiltrating endometriosis, and ureteral endometriosis was diagnosed in 145 of these patients (48.3%). After exclusion from the analysis of the 16 women with a preoperative diagnosis of hydronephrosis, nonobstructive ureteral endometriosis was associated with previous surgery, a posterior nodule with a transverse diameter >1.8 cm, parametrial involvement, and adenomyosis.

Some methodological and clinical considerations might help contextualize the study findings into everyday practice. The diagnostic standards adopted seem somewhat undefined. Ureteral dilatation is a fact, whereas in the absence of hydroureteronephrosis, any criterion that is not objectively measurable inevitably introduces some degree of subjectivity. The investigators argue that in all cases, endometriosis has been histologically demonstrated in lesions adjacent to the ureter and removed during ureterolysis. This is reassuring, but it still may not ensure adequate reproducibility of the diagnosis, and what the interobserver variability would have been if the same women had been operated on by other surgeons is uncertain.

Moreover, in this series, the positive and negative predictive values of the test were 66% and 72%, respectively. Considering the high prevalence of the condition (approximately 50%), these values probably did not markedly change the surgical approach. The prevalence of the index condition influences the predictive values. If the prevalence of ureteral endometriosis decreases, the positive predictive value tends to decrease (for example, to approximately 40% in the case of a prevalence of 25%), but the negative predictive value should increase (and vice versa in cases of higher prevalence). These considerations underline the fact that the result of the “test” should be considered cautiously when planning surgical procedures, especially in hospitals with different prevalence rates of ureteral endometriosis.

In addition, the high prevalence of ureteral endometriosis per se could indicate a selection bias, because women with particularly severe conditions might be referred or self-refer to the investigators’ renowned and highly valued center of expertise. Again, if this is true, the generalizability of the observed results might be limited.

Indeed, the presence of at least three of the four identified predictors, that is, previous surgery, the transverse diameter of a posterior compartment lesion, and parametrial fibrotic infiltration, should always raise the suspicion of possible ureteral involvement. For example, the lateral border of a large rectovaginal lesion might be very close to the distal ureteral tract. For similar anatomic reasons, the risk of ureteral involvement is especially high when endometriotic fibrosis affects the lateral parametria. As the investigators explain, previous surgery may constitute a risk factor, because when the procedure is not performed in a center of expertise, deep lesions that require particularly high technical capabilities to be safely excised are frequently left behind. As a result, women often self-refer to centers of expertise only when repeat surgery is eventually necessary. The identification of adenomyosis as a predictor of ureteral endometriosis could be explained by its observed strong association with deep infiltrating endometriosis (4Marcellin L. Santulli P. Bourdon M. Maignien C. Campin L. Lafay-Pillet M.C. et al.Focal adenomyosis of the outer myometrium and deep infiltrating endometriosis severity.).

According to the investigators, their findings are important, because “the suspicion of ureteral involvement is crucial for the correct surgical planning, requiring an expert surgeon”; “treatment of early lesions can prevent subsequent ureteral stenosis and potentially the loss of renal function”; and correct prediction of the condition allows “extensive preoperative counseling for patients.” These seem three fundamental but partly separate principles that merit distinct consideration.

When almost one in two women turns out to have ureteral endometriosis, it seems sensible to systematically plan the procedure with an expert surgeon who has sufficient training to deal with severe, infiltrating deep lesions wherever they are found and independently from the presence of the identified predictors of ureteral endometriosis. All the women in the present series were operated on by a single, extremely capable surgeon. In such a setting, correctly predicting nonobstructive ureteral involvement may not change the outcome to a great extent, because the women are operated on by the best available surgeon in any case. In less specialized settings, the prediction of ureteral involvement may well be more relevant but, in our opinion, not so much to try to better plan the surgical team, but instead to refer the patient to centers of expertise with the objective of optimizing the efficacy of the procedure and minimizing the risk of complications, two variables that are strictly operator-dependent (1Nezhat C. Falik R. McKinney S. King L.P. Pathophysiology and management of urinary tract endometriosis., 2Barra F. Scala C. Biscaldi E. Vellone V.G. Ceccaroni M. Terrone C. et al.Ureteral endometriosis: a systematic review of epidemiology, pathogenesis, diagnosis, treatment, risk of malignant transformation and fertility., 5Cunha F.L.D. Arcoverde F.V.L. Andres M.P. Gomes D.C. Bautzer C.R.D. Abrao M.S. et al.Laparoscopic treatment of ureteral endometriosis: a systematic review.).One essential clinical message provided by the investigators is that “routine intraoperative retroperitoneal identification and inspection of both ureters is highly advisable in all women undergoing surgery for deep infiltrating endometriosis.” This is a very useful safety maneuver, not only to identify extrinsic ureteral compression but also to prevent inadvertent and potentially unrecognized intraoperative iatrogenic ureteral lesions. However, not all gynecologists are trained to safely perform ureteral isolation and ureterolysis in women with severe deep endometriosis, even when the lesion sites and characteristics are correctly predicted preoperatively (5Cunha F.L.D. Arcoverde F.V.L. Andres M.P. Gomes D.C. Bautzer C.R.D. Abrao M.S. et al.Laparoscopic treatment of ureteral endometriosis: a systematic review.).

It is conceivable that some of the excised infiltrating endometriotic lesions that were externally compressing or distorting the ureter, if not correctly identified and removed, would have progressed and caused stenosis and hydroureteronephrosis in the future. However, this study was not designed to define this outcome, and the preventive value of preoperative identification of ureteral endometriosis without stenosis remains to be determined. Moreover, it would be important to determine the number of women needed to undergo ureterolysis and excision of endometriotic lesions externally compressing the ureter to prevent one case of obstructive uropathy. The associated morbidity, especially when the above procedures are not performed by expert surgeons, should be also included in the overall balance.

All candidates for excision of deep infiltrating endometriotic lesions of the posterior compartment must receive complete, evidence-based, balanced, and quantitative information regarding the expected benefits of the proposed procedures, the types and percentages of risk of complications, including a detailed description of short- and long-term health consequences, and treatment alternatives, independently of lesion diameters or other preoperative predictors of extrinsic ureteral compression without ureteral dilatation. This type of counseling may take time but is of invaluable ethical, psychological, and practical importance. It would be unfortunate if a surgeon who is not concerned about taking much more time at the operating table to pursue radical excision of endometriotic lesions would struggle to add some minutes to the preoperative consultation to empower patients to reach an adequately informed decision.

In conclusion, the investigators should be commended for identifying the above predictors of nonobstructing ureteral endometriosis, because this can translate into increased awareness of the condition, optimal selection of surgeons, and, hence, a potential increase in the efficacy of the procedure and, most notably, improvement in patient safety. Because the most important factor in determining the outcome of surgery for deep endometriotic lesions infiltrating pelvic structures and organs, including the ureter, appears to be the availability of capable gynecologists, abdominal surgeons, and urologists with specific experience in forms of severe endometriosis (2Barra F. Scala C. Biscaldi E. Vellone V.G. Ceccaroni M. Terrone C. et al.Ureteral endometriosis: a systematic review of epidemiology, pathogenesis, diagnosis, treatment, risk of malignant transformation and fertility.), the most profitable use that gynecologists can make of the findings of Arena et al.(3Arena A. Del Forno S. Orsini B. Iodice R. Degli Esposti E. Aru A.C. et al.Ureteral endometriosis, the hidden enemy: multivariable fractional polynomial approach for evaluation of pre-operative risk factors in the absence of ureteral dilatation.) is probably to refer women to tertiary care centers once deep endometriosis with possible ureteral involvement has been preoperatively predicted. In addition, the benefit of being treated in such centers compared with general hospitals could be studied and measured, because the magnitude of such benefit might be larger than that attainable with any predictive algorithm when applied in nonspecialized hospitals.ReferencesNezhat C. Falik R. McKinney S. King L.P.

Pathophysiology and management of urinary tract endometriosis.

Nat Rev Urol. 14: 359-372Barra F. Scala C. Biscaldi E. Vellone V.G. Ceccaroni M. Terrone C. et al.

Ureteral endometriosis: a systematic review of epidemiology, pathogenesis, diagnosis, treatment, risk of malignant transformation and fertility.

Hum Reprod Update. 24: 710-730Arena A. Del Forno S. Orsini B. Iodice R. Degli Esposti E. Aru A.C. et al.

Ureteral endometriosis, the hidden enemy: multivariable fractional polynomial approach for evaluation of pre-operative risk factors in the absence of ureteral dilatation.

Fertil Steril. ()Marcellin L. Santulli P. Bourdon M. Maignien C. Campin L. Lafay-Pillet M.C. et al.

Focal adenomyosis of the outer myometrium and deep infiltrating endometriosis severity.

Fertil Steril. 114: 818-827Cunha F.L.D. Arcoverde F.V.L. Andres M.P. Gomes D.C. Bautzer C.R.D. Abrao M.S. et al.

Laparoscopic treatment of ureteral endometriosis: a systematic review.

J Minim Invas Gynecol. 28: 779-787Article InfoPublication History

Published online: July 03, 2021

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DOI: https://doi.org/10.1016/j.fertnstert.2021.06.014

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©2021 American Society for Reproductive Medicine, Published by Elsevier Inc.

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