- Email: [email protected]
Urinary Tract Endometriosis: Clinical, Diagnostic, and Therapeutic Aspects
Female Urology Urinary Tract Endometriosis: Clinical, Diagnostic, and Therapeutic Aspects Manuel Pérez-Utrilla Pérez, Alfredo Aguilera Bazán, José María Alonso Dorrego, Alicia Hernández, Manuel Girón de Francisco, Mario Martín Hernández, Javier de Santiago, and Javier de la Peña Barthel OBJECTIVES
METHODS RESULTS
CONCLUSIONS
To describe our experience at La Paz University Hospital with 12 patients with urinary tract endometriosis, an uncommon pathologic finding, the most extensive series published by Spanish investigators to our knowledge. We performed a retrospective analysis of 12 cases of urinary tract endometriosis diagnosed from 1993 to 2008. The mean patient age was 37.75 years. Of the 12 patients, 5 had bladder involvement and 7 had ureteral involvement, 2 bilateral, 2 left, and 3 right. In those with bladder endometriosis, the diagnosis was made by cystoscopy and biopsy in 4 patients. Treatment consisted of laparoscopic hysterectomy and partial cystectomy in 1 patient and exploratory laparotomy, transvesical resection, and transurethral resection of the bladder in 3 patients. One of the patients who underwent transurethral resection of the bladder experienced 2 relapses. The first relapse was treated with transurethral resection of the bladder and the second with laparoscopic partial cystectomy. In the patients with ureteral endometriosis, the diagnosis was mainly established by magnetic resonance imaging. Treatment consisted of ureteroneocystostomy in 5 patients (bilateral in 1) and laparoscopic ureterolysis in 2, with later ureteral resection and end-to-end anastomosis in 1 of them. The patient who underwent bilateral ureteroneocystostomy finally required right autotransplantation because of early ureteral relapses. Urinary tract endometriosis is an uncommon pathologic finding. Surgery is the treatment of choice. We believe partial cystectomy should be considered as an initial option in selected cases, depending on the extent and location of lesions. For cases of ureteral endometriosis, the initial technique depends on the location and depth of the lesion. UROLOGY 73: 47–51, 2009. © 2009 Elsevier Inc.
E
ndometriosis is a condition in which endometrial tissue, glands, or stroma is found outside the normal limits of the myometrium or uterine cavity. The disorder is most often seen in young women (aged 25-35 years). Endometriosis has been estimated to affect 4%-15% of all women with child-bearing potential,1 and is the most frequent pelvic gynecologic disorder. The pelvic region is the most common location— particularly, the ovaries and the broad ligament. Cases have also been reported with locations far removed from the pelvic region, such as the lungs and gastrointestinal tract. Urinary tract involvement is uncommon, with a variable incidence reported. In this context, the bladder is the most common location,2 representing 84% of all cases of urinary tract endometriosis.
The present report describes our experience, with the contribution of 12 new patients. This is the most extensive series published by Spanish investigators to date, to our knowledge.
MATERIAL AND METHODS From January 2001 to January 2008, 10 cases of urinary tract endometriosis were diagnosed. Two additional patients were incorporated into this study, 1 diagnosed in 1993 and the other in 1997, for a total of 12 patients. Seven patients had been referred from the Department of Gynecology, 1 from the Department of Nephrology, and 4 were initially evaluated in the Department of Urology.
RESULTS From the Departments of Urology and Gynecology, La Paz University Hospital, Madrid, Spain Reprint requests: Servicio de Urología. Hospital Universitario La Paz, Paseo de la Castellana 261, Madrid 28046 Spain. E-mail: [email protected] Submitted: June 11, 2008, accepted (with revisions): August 11, 2008
© 2009 Elsevier Inc. All Rights Reserved
The mean patient age was 37.75 years (range 30-45). One third of the patients had a history of endometriosis in some other location before diagnosis. Three patients (25%) were nulliparous. Of the remaining 9 women, 4 had undergone cesarean section (33% of the series). Of 0090-4295/09/$34.00 doi:10.1016/j.urology.2008.08.470
47
Table 1. Treatment and follow-up of patients with bladder endometriosis Pt. No.
Surgical Procedure
Relapse/Follow-up (mo)
1 2 3 4 5
Hysterectomy ⫹ laparoscopic partial cystectomy Transurethral resection of the bladder Laparotomy ⫹ transvesical resection Transurethral resection of the bladder Transurethral resection of the bladder Transurethral resection of the bladder Hysterectomy, bilateral adnexectomy, and laparoscopic partial cystectomy
No/14 No/168 No/36; lost to follow-up No/68 Yes/42 Yes/20
Pt. No., patient number.
Table 2. Treatment and follow-up of patients with ureteral endometriosis Relapse/ Follow-up
Pt. No.
Treatment
1
No/12
4 5
H ⫹ RtA ⫹ LtUR ⫹ LtUNC ⫹ sigmoid resection ⫹ colorectal anastomosis LtUR ⫹ LtUNC H ⫹ LtA ⫹ laparoscopic right ureterolysis Right colic pain in immediate postoperative period: RtUR ⫹ EEUA ⫹ right double J stent RtUR ⫹ RtUNC BUR ⫹ BUNC
6 7
LtUR ⫹ LtUNC Laparoscopic right ureterolysis
No/15 No/3
2 3
No/71 No/13
No/36 Yes/23
Complications Bilateral involvement; preoperative IVU and renogram showed right functional annulment Lost to follow-up Right obstructive uropathy 2 mo, right PN 7 mo, RtUNC 9 mo, good bilateral kidney function Lost to follow-up 2 mo, obstructive uropathy: bilateral double J stent 4 mo, after removal of stent, repeat obstructive uropathy: left double J stent ⫹ right PN 16 mo, intestinal relapse: rectosigmoid resection ⫹ coloanal anastomosis 22 mo, right ureteral relapse: RtUR ⫹ autotransplant of right iliac fossa None Ureterovaginal fistula, right PN
Pt. No. ⫽ patient number; H, hysterectomy; Rt, right; A, adnexectomy; Lt, left; UR, ureteral resection; UNC, ureteroneocystostomy; IVU, intravenous urography; EEAU, end-to-end ureteral anastomosis; PN, percutaneous nephrostomy; BUR, bilateral ureteral resection.
the 12 patients, 5 had bladder involvement (retrotrigone in 2, trigone in 1, and posterior surface/bladder fundus in 2) and 7 had ureteral and periureteral involvement (2 bilateral, 2 left, and 3 right). In all patients, the distal third was the affected zone. Of the 7 patients with ureteral foci, 4 (57%) had previously undergone pelvic surgery compared with 3 of the 5 patients (60%) with bladder endometriosis. For the patients with bladder endometriosis, the most common initial manifestation was cyclic micturition syndrome (60%). The diagnosis was confirmed by cystoscopy and biopsy in 4 of the 5 patients. In fifth patient, abdominal ultrasonography revealed the perivesical mass, which mainly affected the posterior surface of the bladder. Exploratory laparoscopy was indicated, with biopsy and resection of the endometriosis lesion. Treatment consisted of the operations listed in Table 1. Three patients were treated with adjuvant gonadotropin-releasing hormone analogs. For the 7 patients with ureteral endometriosis, the most common manifestation was lumbar pain (71%). The diagnosis was established by pelvic magnetic resonance imaging (MRI) in 4 patients. The treatment is listed in Table 2. In 1 of the patients with bilateral involvement, bilateral ureteral resection was done with bilateral ureteroneocystostomy posteriorly. This patient 48
required urinary bypass owing to early relapse at 2 months, extensive intestinal resection because of intestinal relapse at 16 months, and finally autotransplantation (Fig. 1) in the right iliac fossa.
COMMENT Endometriosis is the most common gynecologic disorder in women.3 It represents the most common gynecologic diagnosis in hospitalized women aged 15-44 years.4 The estimated prevalence of endometriosis is 10%-20% for the general female population,5 3%-10% for women with child-bearing potential (20-45 years), and ⱕ25%-35% for infertile women.6 Some investigators7 have reported urologic involvement in 15%-25% of all cases, although this range appears rather exaggerated. No large series have been reported in support of these data. Ball and Platt8 reported that only 1.2%-3.9% of all women with endometriosis have urologic involvement producing symptoms or requiring treatment, with this reduced group of patients the subject of different scientific reports. Endometriosis has been reported in a broad range of locations, although the pelvis has been the most commonly affected region. It is mainly found in the ovaries (54%), broad ligament (35%), Douglas sac (35%), and uterosacral ligaments (8%).9 Studies have also reported UROLOGY 73 (1), 2009
Figure 1. Bilateral pyelography after distal right ureteral resection and autotransplantation.
locations far removed from the genitourinary apparatus, including the lungs,10 skin,11 and digestive tract.12 Within the urinary system, the bladder is the most commonly affected (80%-84%), followed by the ureter (15%), kidney (4%), and urethra (2%).13 In the bladder, the retrotrigone and dome are the most frequently affected sites. Two possible ureteral lesions must be considered: intrinsic and extrinsic. The extrinsic form is more common and is characterized by contiguity involvement of the ureter, compressing and causing fibrosis of the ureteral structures, and impairing function of the kidney in ⱕ30% of cases. The intrinsic lesions originate from lymphatic or venous metastases14 and can manifest as obstructive conditions or result in cyclic hematuria when the ureteral mucosa is affected.6 The symptoms generated by endometriosis are very nonspecific. As a result, the diagnosis must be determined from an adequate compilation of the clinical history and a thorough physical examination. However, most patients with endometriosis will have normal physical examination findings. Logically, the symptoms depend on the location and depth of infiltration of the endometriosis lesion. Chapron15 considered pelvic endometriosis to be the cause of 25%-35% of all cyclic, chronic pelvic pain conditions. Regarding urinary manifestations, patients with bladder involvement usually present with micturition syndrome (usually of a cyclical nature), dysuria, and increased micturition frequency. Urinary urgency and micturition frequency predominate. Menuria (hematuria UROLOGY 73 (1), 2009
coinciding with the menstrual cycle) is less frequent,7 occurring in 20% of cases. The endometrial focus infiltrates the bladder from the pericystium toward the mucosa, from outside to inside. In some cases, the mucosa is not affected—thus, explaining the absence of hematuria in some patients. It seems logical that bladder endometriosis might be underdiagnosed for this same reason, because the micturition syndrome can be mild. In our series, the main symptom was cyclical micturition syndrome (3 patients), although dysmenorrhea or chronic pelvic pain was also present. When the ureter is affected, the symptoms depend on whether the lesion is intrinsic or extrinsic. The most common presentation is the absence of symptoms, with no symptoms in ⱕ50% of patients with ureteral endometriosis,4 followed by abdominal or lumbar pain (owing to secondary obstruction). In our experience, 2 cases corresponded to an incidental diagnosis, and the rest of the patients presented with lumbar or pelvic pain. With renal involvement, the most common manifestation is lumbar pain, although the condition can be asymptomatic and can be incidentally diagnosed as renal masses of different sizes.16 Imaging techniques can be used to confirm the clinical diagnosis or contribute to the preoperative workup. Ultrasonography should be used in the initial evaluation. Although it is very useful for differentiating solid lesions from cystic cavities, the findings are quite variable and, in some cases, can simulate benign or malignant lesions, fundamentally when evaluating the adnexa, such as dermoid cysts, hemorrhagic cysts, or tumors. In view of this important lack of specificity, some investigators consider endometriosis to be the most difficult adnexal lesion to diagnose on the basis of the ultrasound findings alone.17 The technique with the greatest specificity in identifying endometriosis lesions is MRI.18 MRI outperforms computed tomography and is able to more precisely define the magnitude of the lesions, as well as their depth. As observed in our center, MRI was of demonstrated usefulness, contributing to the diagnosis of 4 of the 7 patients with ureteral involvement. When suspecting urinary endometriosis, urologists should request intravenous urography. The upper urinary tract should be evaluated in all patients with pelvic endometriosis to exclude asymptomatic ureteral involvement.19 However, functional annulment of the affected kidney is a common finding on intravenous urography.4 In our series, the diagnosis of 3 of the 7 patients with ureteral involvement was determined from the combination of ultrasonography and intravenous urography. Adequate endoscopic exploration is of great importance. Cystoscopy and/or ureteroscopy not only allow for direction observation of the bladder and/or ureteral lesions, but can also offer histologic material to confirm the diagnosis. One should remember that the macroscopic appearance of the lesions changes with the different phases of the menstrual cycle.19 During actual menstruation, the lesions appear more congested and edematous. 49
In addition, if the ectopic tissue does not extend beyond the pericystium or ureteral adventitial layer, endoscopy will be of little use. Thus, negative endoscopic findings do not necessarily imply the absence of urinary endometriosis. The management of endometriosis depends on the severity of the symptoms, the extent of the disease and its location, and the age of the patient and her desire for future fertility. Medical treatment is based on modifying the endometrial tissue response to hormonal stimulation. Use can be made of a combination of estrogens and progesterone, or of progesterogenic agents, to induce pseudopregnancy.4 Among the drugs most commonly used for this purpose, are medroxyprogesterone acetate and oral contraceptives.20 With small bladder lesions, use has been made of these drugs with partial or complete symptom remission.21 However, the relapse rate in pelvic endometriosis is quite high (ⱕ56%),22 revealing that such treatment only induces a temporary disappearance of the lesions in patients with deep endometriosis. Gonadotropin inhibitors such as danazol reduce the production of folliclestimulating hormone and luteinizing hormone halfway through the cycle—thereby inducing an anovulatory state. A range of side effects has been reported, including skin rash, nausea, diaphoresis, irritability, hot flashes, and androgenic symptoms (hirsutism, acne, oily skin, vocal changes).23 Another option is the use of gonadotropinreleasing hormone analogs, producing hypogonadism after a transient increase in follicle-stimulating hormone and luteinizing hormone levels. Such hypogonadotropic hypogonadism will induce a decrease in the serum estrogen levels to castration levels—triggering anovulation and endometrial tissue regression.24 In our experience, 3 patients with bladder endometriosis were treated with gonadotropin-releasing hormone analogs—in all cases as an adjuvant to surgery. One of these 3 patients suspended the treatment after the second dose because of intolerance. The treatment was indicated after the second transurethral bladder resection, with another relapse after 20 months. The other 2 patients had no relapses or drug tolerance problems. Of the patients with ureteral endometriosis, danazol was prescribed in 1 patient with bilateral and very relapse-prone disease. Her tolerability was good, despite the side effects, which were of mild severity. However, surgical treatment offers better results than clinical management. In a recent study comparing clinical management and surgery for bladder endometriosis, 14 of 16 patients who underwent hormonal therapy developed relapses compared with 0 of the 21 patients who underwent surgery.22 Another aspect to consider is the women who do not wish to preserve fertility or elderly patients, for whom the definitive treatment is surgical castration in the form of hysterectomy and bilateral adnexectomy. When an ovary is preserved, the reintervention rate is eightfold greater.25 50
The surgical treatment modalities for bladder endometriosis have been debated. Some investigators have advocated transurethral resection of the bladder plus medical treatment as the treatment of choice, although a relapse rate of ⱕ35% has been reported with this approach.26 It seems logical that because of the transmural nature of endometriosis, complete transurethral resection would imply bladder perforation. From our experience, and in agreement with Antonelli et al.,27 the recommended approach is partial cystectomy— either open or laparoscopic, depending on surgeon expertise, and depending on the location of the lesion and the patient characteristics. The obstruction produced by ureteral endometriosis is responsible for the associated symptoms, and the severity of the condition, its nature (extrinsic or intrinsic) and location, and the patient’s clinical characteristics, in turn, determine the surgical approach. The obstruction can be resolved by ureterolysis, resection, or nephrectomy. Ureterolysis should be reserved for those cases with limited and nonobstructive ureteral involvement.28 The main limitation of the technique is the possibility of relapse in the event of incomplete surgery and the risk of persistent endometrial tissue. If resection is chosen, ureteral continuity must be restored, with the technique determined according to the location and length of the resected ureteral segment. We believe distal ureteral involvement should be managed with ureteral resection and ureteroneocystostomy, thereby avoiding use of the urinary tract distal to the affected zone. When the lesion lies more proximal or its length is greater, other options include ileal interpositioning or autotransplantation. Of the 5 patients who underwent ureteral resection and ureteroneocystostomy, only 1 developed disease relapse and required autotransplantation owing to the important length of ureter affected.
CONCLUSIONS Urinary tract endometriosis is an uncommon condition. The symptoms are nonspecific, and this is why a meticulous patient history is extremely important. Of the possible urinary locations, bladder endometriosis is the most common presentation. In such cases, it is particularly important to obtain a biopsy by way of cystoscopy at the appropriate moment. MRI is the imaging technique that best characterizes these lesions. Surgery is the treatment of choice. We believe partial cystectomy should be consider in selected patients as the initial option because of the transmural nature of bladder endometriosis. In cases of ureteral endometriosis, the initial technique is determined by the location and depth of the lesion. References 1. Schwartzwald D, Mooppan U, Ohm HK, et al. Endometriosis of bladder. Urology. 1992;39:219-222. 2. Vercellini P, Meschia M, De Giorgio O, et al. Bladder detrusor endometriosis: Clinical and pathogenetic implications. J Urol. 1996;155:770-771.
UROLOGY 73 (1), 2009
3. Bologna RA, Whitmore KE. Genitourinary endometriosis. AUA Update Series. 2001;1:21. 4. Comiter CV. Endometriosis of the urinary tract. Urol Clin North Am. 2002;29:625-635. 5. Vessey MP, Villard-Mackintosh L, Painter R. Epidemiology of endometriosis in women attending family planning clinics. BMJ. 1993;306:182-184. 6. Llerena Ibarguren R, Lecumberri Castaños D, Padilla Nieva J, et al. Endometrioma urinario. Arch Esp Urol. 2002;55:1209-1215. 7. Shook TE, Nyberg LM. Endometriosis of the urinary tract. Urology. 1988;31:1-6. 8. Ball TL, Platt MA. Urologic complications of endometriosis. Am J Obstet Gynecol. 1962;84:1516-1521. 9. Pastor Navarro H, Donate Moreno MJ, Giménez Basch JM, et al. Endometriosis vesical: Revisión de la literatura, con especial referencia a la española y aportación de dos nuevos casos. Arc Esp Urol. 2006;59:111-122. 10. Park YB, Heo GM, Moon HK, et al. Pulmonary endometriosis resected by video-assisted thoracoscopic surgery. Respirology. 2006; 11:221-223. 11. Catalina-Fernandez I, Lopez-Presa D, Saenz-Santamaria J. Fine needle aspiration cytology in cutaneous and subcutaneous endometriosis. Acta Cytol. 2007;51:380-384. 12. Tumay V, Ozturk E, Ozturk H, et al. Appendiceal endometriosis mimicking acute appendicitis. Acta Chir Belg. 2006;106:712713. 13. Dones J, Spada F, Squifflet J, et al. Bladder endometriosis must be considered as bladder adenomyosis. Fertil Steril. 2000;74:1175-1181. 14. Fujita K. Endometriosis of the ureter. J Urol. 1976;116:664-666. 15. Chapron C. Doleur et endometriose profonde. J Gynecol Biol Reprod 2003;32:32-36.
UROLOGY 73 (1), 2009
16. Bazaz-Malik G, Saraf V, Rana BS. Endometriosis of the kidney. J Urol. 1980;123:422-423. 17. Woodward PJ, Sohaey R, Mezzeti TP. Endometriosis: Radiologic– pathologic correlation. Radiographics. 2001;21:193-216. 18. Togashi K, Nishimura K, Kimura I, et al. Endometrial cysts: Diagnosis with MR imaging. Radiology. 1991;180:73-78. 19. Monllor GJ, Merino Hernaez C, Oliver Gómez, et al. Endometriosis vesical, aproximación diagnóstica y terapeútica. Acta Urol Esp. 1991;15:86-89. 20. Olive DL, Pritts EA. Treatment of endometriosis. N Engl J Med. 2001;345:266-275. 21. Westney OL, Amundsen CL, McGuire EJ. Bladder endometriosis: Conservative management. J Urol. 2000;163:1814-1817. 22. Price DT, Maloney KE, Ibrahim GK, et al. Vesical endometriosis: Report of two cases and review of the literature. Urology. 1996;48: 639-643. 23. Cohen MR. Laparoscopic diagnosis and pseudomenopause treatment of endometriosis with danazol. Clin Obstet Gynecol. 1980;23: 901-904. 24. Goebel R, Rjosk HK. Laboratory and clinical studies with the new antigonadotropin, danazol. Acta Endocrinol Suppl. 1977;212:134135. 25. Nannoum AB, Hickman TN, Goodman SB, et al. Incidence of symptom recurrence after hysterectomy for endometriosis. Fertil Steril. 1995;64:898-902. 26. Sánchez Merino JM, Guillan Maquieira C, Alonso G, et al. Endometriosis vesical: Revisión de la literatura española. Arch Esp Urol. 2005;58:189-194. 27. Antonelli A, Simeone C, Zani D, et al. Clinical aspects and surgical treatment of urinary tract endometriosis: Our experience with 31 cases. Eur Urol. 2006;49:1093-1097. 28. Yohannes P. Ureteral endometriosis. J Urol. 2003;170:20-25.
51
METHODS RESULTS
CONCLUSIONS
To describe our experience at La Paz University Hospital with 12 patients with urinary tract endometriosis, an uncommon pathologic finding, the most extensive series published by Spanish investigators to our knowledge. We performed a retrospective analysis of 12 cases of urinary tract endometriosis diagnosed from 1993 to 2008. The mean patient age was 37.75 years. Of the 12 patients, 5 had bladder involvement and 7 had ureteral involvement, 2 bilateral, 2 left, and 3 right. In those with bladder endometriosis, the diagnosis was made by cystoscopy and biopsy in 4 patients. Treatment consisted of laparoscopic hysterectomy and partial cystectomy in 1 patient and exploratory laparotomy, transvesical resection, and transurethral resection of the bladder in 3 patients. One of the patients who underwent transurethral resection of the bladder experienced 2 relapses. The first relapse was treated with transurethral resection of the bladder and the second with laparoscopic partial cystectomy. In the patients with ureteral endometriosis, the diagnosis was mainly established by magnetic resonance imaging. Treatment consisted of ureteroneocystostomy in 5 patients (bilateral in 1) and laparoscopic ureterolysis in 2, with later ureteral resection and end-to-end anastomosis in 1 of them. The patient who underwent bilateral ureteroneocystostomy finally required right autotransplantation because of early ureteral relapses. Urinary tract endometriosis is an uncommon pathologic finding. Surgery is the treatment of choice. We believe partial cystectomy should be considered as an initial option in selected cases, depending on the extent and location of lesions. For cases of ureteral endometriosis, the initial technique depends on the location and depth of the lesion. UROLOGY 73: 47–51, 2009. © 2009 Elsevier Inc.
E
ndometriosis is a condition in which endometrial tissue, glands, or stroma is found outside the normal limits of the myometrium or uterine cavity. The disorder is most often seen in young women (aged 25-35 years). Endometriosis has been estimated to affect 4%-15% of all women with child-bearing potential,1 and is the most frequent pelvic gynecologic disorder. The pelvic region is the most common location— particularly, the ovaries and the broad ligament. Cases have also been reported with locations far removed from the pelvic region, such as the lungs and gastrointestinal tract. Urinary tract involvement is uncommon, with a variable incidence reported. In this context, the bladder is the most common location,2 representing 84% of all cases of urinary tract endometriosis.
The present report describes our experience, with the contribution of 12 new patients. This is the most extensive series published by Spanish investigators to date, to our knowledge.
MATERIAL AND METHODS From January 2001 to January 2008, 10 cases of urinary tract endometriosis were diagnosed. Two additional patients were incorporated into this study, 1 diagnosed in 1993 and the other in 1997, for a total of 12 patients. Seven patients had been referred from the Department of Gynecology, 1 from the Department of Nephrology, and 4 were initially evaluated in the Department of Urology.
RESULTS From the Departments of Urology and Gynecology, La Paz University Hospital, Madrid, Spain Reprint requests: Servicio de Urología. Hospital Universitario La Paz, Paseo de la Castellana 261, Madrid 28046 Spain. E-mail: [email protected] Submitted: June 11, 2008, accepted (with revisions): August 11, 2008
© 2009 Elsevier Inc. All Rights Reserved
The mean patient age was 37.75 years (range 30-45). One third of the patients had a history of endometriosis in some other location before diagnosis. Three patients (25%) were nulliparous. Of the remaining 9 women, 4 had undergone cesarean section (33% of the series). Of 0090-4295/09/$34.00 doi:10.1016/j.urology.2008.08.470
47
Table 1. Treatment and follow-up of patients with bladder endometriosis Pt. No.
Surgical Procedure
Relapse/Follow-up (mo)
1 2 3 4 5
Hysterectomy ⫹ laparoscopic partial cystectomy Transurethral resection of the bladder Laparotomy ⫹ transvesical resection Transurethral resection of the bladder Transurethral resection of the bladder Transurethral resection of the bladder Hysterectomy, bilateral adnexectomy, and laparoscopic partial cystectomy
No/14 No/168 No/36; lost to follow-up No/68 Yes/42 Yes/20
Pt. No., patient number.
Table 2. Treatment and follow-up of patients with ureteral endometriosis Relapse/ Follow-up
Pt. No.
Treatment
1
No/12
4 5
H ⫹ RtA ⫹ LtUR ⫹ LtUNC ⫹ sigmoid resection ⫹ colorectal anastomosis LtUR ⫹ LtUNC H ⫹ LtA ⫹ laparoscopic right ureterolysis Right colic pain in immediate postoperative period: RtUR ⫹ EEUA ⫹ right double J stent RtUR ⫹ RtUNC BUR ⫹ BUNC
6 7
LtUR ⫹ LtUNC Laparoscopic right ureterolysis
No/15 No/3
2 3
No/71 No/13
No/36 Yes/23
Complications Bilateral involvement; preoperative IVU and renogram showed right functional annulment Lost to follow-up Right obstructive uropathy 2 mo, right PN 7 mo, RtUNC 9 mo, good bilateral kidney function Lost to follow-up 2 mo, obstructive uropathy: bilateral double J stent 4 mo, after removal of stent, repeat obstructive uropathy: left double J stent ⫹ right PN 16 mo, intestinal relapse: rectosigmoid resection ⫹ coloanal anastomosis 22 mo, right ureteral relapse: RtUR ⫹ autotransplant of right iliac fossa None Ureterovaginal fistula, right PN
Pt. No. ⫽ patient number; H, hysterectomy; Rt, right; A, adnexectomy; Lt, left; UR, ureteral resection; UNC, ureteroneocystostomy; IVU, intravenous urography; EEAU, end-to-end ureteral anastomosis; PN, percutaneous nephrostomy; BUR, bilateral ureteral resection.
the 12 patients, 5 had bladder involvement (retrotrigone in 2, trigone in 1, and posterior surface/bladder fundus in 2) and 7 had ureteral and periureteral involvement (2 bilateral, 2 left, and 3 right). In all patients, the distal third was the affected zone. Of the 7 patients with ureteral foci, 4 (57%) had previously undergone pelvic surgery compared with 3 of the 5 patients (60%) with bladder endometriosis. For the patients with bladder endometriosis, the most common initial manifestation was cyclic micturition syndrome (60%). The diagnosis was confirmed by cystoscopy and biopsy in 4 of the 5 patients. In fifth patient, abdominal ultrasonography revealed the perivesical mass, which mainly affected the posterior surface of the bladder. Exploratory laparoscopy was indicated, with biopsy and resection of the endometriosis lesion. Treatment consisted of the operations listed in Table 1. Three patients were treated with adjuvant gonadotropin-releasing hormone analogs. For the 7 patients with ureteral endometriosis, the most common manifestation was lumbar pain (71%). The diagnosis was established by pelvic magnetic resonance imaging (MRI) in 4 patients. The treatment is listed in Table 2. In 1 of the patients with bilateral involvement, bilateral ureteral resection was done with bilateral ureteroneocystostomy posteriorly. This patient 48
required urinary bypass owing to early relapse at 2 months, extensive intestinal resection because of intestinal relapse at 16 months, and finally autotransplantation (Fig. 1) in the right iliac fossa.
COMMENT Endometriosis is the most common gynecologic disorder in women.3 It represents the most common gynecologic diagnosis in hospitalized women aged 15-44 years.4 The estimated prevalence of endometriosis is 10%-20% for the general female population,5 3%-10% for women with child-bearing potential (20-45 years), and ⱕ25%-35% for infertile women.6 Some investigators7 have reported urologic involvement in 15%-25% of all cases, although this range appears rather exaggerated. No large series have been reported in support of these data. Ball and Platt8 reported that only 1.2%-3.9% of all women with endometriosis have urologic involvement producing symptoms or requiring treatment, with this reduced group of patients the subject of different scientific reports. Endometriosis has been reported in a broad range of locations, although the pelvis has been the most commonly affected region. It is mainly found in the ovaries (54%), broad ligament (35%), Douglas sac (35%), and uterosacral ligaments (8%).9 Studies have also reported UROLOGY 73 (1), 2009
Figure 1. Bilateral pyelography after distal right ureteral resection and autotransplantation.
locations far removed from the genitourinary apparatus, including the lungs,10 skin,11 and digestive tract.12 Within the urinary system, the bladder is the most commonly affected (80%-84%), followed by the ureter (15%), kidney (4%), and urethra (2%).13 In the bladder, the retrotrigone and dome are the most frequently affected sites. Two possible ureteral lesions must be considered: intrinsic and extrinsic. The extrinsic form is more common and is characterized by contiguity involvement of the ureter, compressing and causing fibrosis of the ureteral structures, and impairing function of the kidney in ⱕ30% of cases. The intrinsic lesions originate from lymphatic or venous metastases14 and can manifest as obstructive conditions or result in cyclic hematuria when the ureteral mucosa is affected.6 The symptoms generated by endometriosis are very nonspecific. As a result, the diagnosis must be determined from an adequate compilation of the clinical history and a thorough physical examination. However, most patients with endometriosis will have normal physical examination findings. Logically, the symptoms depend on the location and depth of infiltration of the endometriosis lesion. Chapron15 considered pelvic endometriosis to be the cause of 25%-35% of all cyclic, chronic pelvic pain conditions. Regarding urinary manifestations, patients with bladder involvement usually present with micturition syndrome (usually of a cyclical nature), dysuria, and increased micturition frequency. Urinary urgency and micturition frequency predominate. Menuria (hematuria UROLOGY 73 (1), 2009
coinciding with the menstrual cycle) is less frequent,7 occurring in 20% of cases. The endometrial focus infiltrates the bladder from the pericystium toward the mucosa, from outside to inside. In some cases, the mucosa is not affected—thus, explaining the absence of hematuria in some patients. It seems logical that bladder endometriosis might be underdiagnosed for this same reason, because the micturition syndrome can be mild. In our series, the main symptom was cyclical micturition syndrome (3 patients), although dysmenorrhea or chronic pelvic pain was also present. When the ureter is affected, the symptoms depend on whether the lesion is intrinsic or extrinsic. The most common presentation is the absence of symptoms, with no symptoms in ⱕ50% of patients with ureteral endometriosis,4 followed by abdominal or lumbar pain (owing to secondary obstruction). In our experience, 2 cases corresponded to an incidental diagnosis, and the rest of the patients presented with lumbar or pelvic pain. With renal involvement, the most common manifestation is lumbar pain, although the condition can be asymptomatic and can be incidentally diagnosed as renal masses of different sizes.16 Imaging techniques can be used to confirm the clinical diagnosis or contribute to the preoperative workup. Ultrasonography should be used in the initial evaluation. Although it is very useful for differentiating solid lesions from cystic cavities, the findings are quite variable and, in some cases, can simulate benign or malignant lesions, fundamentally when evaluating the adnexa, such as dermoid cysts, hemorrhagic cysts, or tumors. In view of this important lack of specificity, some investigators consider endometriosis to be the most difficult adnexal lesion to diagnose on the basis of the ultrasound findings alone.17 The technique with the greatest specificity in identifying endometriosis lesions is MRI.18 MRI outperforms computed tomography and is able to more precisely define the magnitude of the lesions, as well as their depth. As observed in our center, MRI was of demonstrated usefulness, contributing to the diagnosis of 4 of the 7 patients with ureteral involvement. When suspecting urinary endometriosis, urologists should request intravenous urography. The upper urinary tract should be evaluated in all patients with pelvic endometriosis to exclude asymptomatic ureteral involvement.19 However, functional annulment of the affected kidney is a common finding on intravenous urography.4 In our series, the diagnosis of 3 of the 7 patients with ureteral involvement was determined from the combination of ultrasonography and intravenous urography. Adequate endoscopic exploration is of great importance. Cystoscopy and/or ureteroscopy not only allow for direction observation of the bladder and/or ureteral lesions, but can also offer histologic material to confirm the diagnosis. One should remember that the macroscopic appearance of the lesions changes with the different phases of the menstrual cycle.19 During actual menstruation, the lesions appear more congested and edematous. 49
In addition, if the ectopic tissue does not extend beyond the pericystium or ureteral adventitial layer, endoscopy will be of little use. Thus, negative endoscopic findings do not necessarily imply the absence of urinary endometriosis. The management of endometriosis depends on the severity of the symptoms, the extent of the disease and its location, and the age of the patient and her desire for future fertility. Medical treatment is based on modifying the endometrial tissue response to hormonal stimulation. Use can be made of a combination of estrogens and progesterone, or of progesterogenic agents, to induce pseudopregnancy.4 Among the drugs most commonly used for this purpose, are medroxyprogesterone acetate and oral contraceptives.20 With small bladder lesions, use has been made of these drugs with partial or complete symptom remission.21 However, the relapse rate in pelvic endometriosis is quite high (ⱕ56%),22 revealing that such treatment only induces a temporary disappearance of the lesions in patients with deep endometriosis. Gonadotropin inhibitors such as danazol reduce the production of folliclestimulating hormone and luteinizing hormone halfway through the cycle—thereby inducing an anovulatory state. A range of side effects has been reported, including skin rash, nausea, diaphoresis, irritability, hot flashes, and androgenic symptoms (hirsutism, acne, oily skin, vocal changes).23 Another option is the use of gonadotropinreleasing hormone analogs, producing hypogonadism after a transient increase in follicle-stimulating hormone and luteinizing hormone levels. Such hypogonadotropic hypogonadism will induce a decrease in the serum estrogen levels to castration levels—triggering anovulation and endometrial tissue regression.24 In our experience, 3 patients with bladder endometriosis were treated with gonadotropin-releasing hormone analogs—in all cases as an adjuvant to surgery. One of these 3 patients suspended the treatment after the second dose because of intolerance. The treatment was indicated after the second transurethral bladder resection, with another relapse after 20 months. The other 2 patients had no relapses or drug tolerance problems. Of the patients with ureteral endometriosis, danazol was prescribed in 1 patient with bilateral and very relapse-prone disease. Her tolerability was good, despite the side effects, which were of mild severity. However, surgical treatment offers better results than clinical management. In a recent study comparing clinical management and surgery for bladder endometriosis, 14 of 16 patients who underwent hormonal therapy developed relapses compared with 0 of the 21 patients who underwent surgery.22 Another aspect to consider is the women who do not wish to preserve fertility or elderly patients, for whom the definitive treatment is surgical castration in the form of hysterectomy and bilateral adnexectomy. When an ovary is preserved, the reintervention rate is eightfold greater.25 50
The surgical treatment modalities for bladder endometriosis have been debated. Some investigators have advocated transurethral resection of the bladder plus medical treatment as the treatment of choice, although a relapse rate of ⱕ35% has been reported with this approach.26 It seems logical that because of the transmural nature of endometriosis, complete transurethral resection would imply bladder perforation. From our experience, and in agreement with Antonelli et al.,27 the recommended approach is partial cystectomy— either open or laparoscopic, depending on surgeon expertise, and depending on the location of the lesion and the patient characteristics. The obstruction produced by ureteral endometriosis is responsible for the associated symptoms, and the severity of the condition, its nature (extrinsic or intrinsic) and location, and the patient’s clinical characteristics, in turn, determine the surgical approach. The obstruction can be resolved by ureterolysis, resection, or nephrectomy. Ureterolysis should be reserved for those cases with limited and nonobstructive ureteral involvement.28 The main limitation of the technique is the possibility of relapse in the event of incomplete surgery and the risk of persistent endometrial tissue. If resection is chosen, ureteral continuity must be restored, with the technique determined according to the location and length of the resected ureteral segment. We believe distal ureteral involvement should be managed with ureteral resection and ureteroneocystostomy, thereby avoiding use of the urinary tract distal to the affected zone. When the lesion lies more proximal or its length is greater, other options include ileal interpositioning or autotransplantation. Of the 5 patients who underwent ureteral resection and ureteroneocystostomy, only 1 developed disease relapse and required autotransplantation owing to the important length of ureter affected.
CONCLUSIONS Urinary tract endometriosis is an uncommon condition. The symptoms are nonspecific, and this is why a meticulous patient history is extremely important. Of the possible urinary locations, bladder endometriosis is the most common presentation. In such cases, it is particularly important to obtain a biopsy by way of cystoscopy at the appropriate moment. MRI is the imaging technique that best characterizes these lesions. Surgery is the treatment of choice. We believe partial cystectomy should be consider in selected patients as the initial option because of the transmural nature of bladder endometriosis. In cases of ureteral endometriosis, the initial technique is determined by the location and depth of the lesion. References 1. Schwartzwald D, Mooppan U, Ohm HK, et al. Endometriosis of bladder. Urology. 1992;39:219-222. 2. Vercellini P, Meschia M, De Giorgio O, et al. Bladder detrusor endometriosis: Clinical and pathogenetic implications. J Urol. 1996;155:770-771.
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3. Bologna RA, Whitmore KE. Genitourinary endometriosis. AUA Update Series. 2001;1:21. 4. Comiter CV. Endometriosis of the urinary tract. Urol Clin North Am. 2002;29:625-635. 5. Vessey MP, Villard-Mackintosh L, Painter R. Epidemiology of endometriosis in women attending family planning clinics. BMJ. 1993;306:182-184. 6. Llerena Ibarguren R, Lecumberri Castaños D, Padilla Nieva J, et al. Endometrioma urinario. Arch Esp Urol. 2002;55:1209-1215. 7. Shook TE, Nyberg LM. Endometriosis of the urinary tract. Urology. 1988;31:1-6. 8. Ball TL, Platt MA. Urologic complications of endometriosis. Am J Obstet Gynecol. 1962;84:1516-1521. 9. Pastor Navarro H, Donate Moreno MJ, Giménez Basch JM, et al. Endometriosis vesical: Revisión de la literatura, con especial referencia a la española y aportación de dos nuevos casos. Arc Esp Urol. 2006;59:111-122. 10. Park YB, Heo GM, Moon HK, et al. Pulmonary endometriosis resected by video-assisted thoracoscopic surgery. Respirology. 2006; 11:221-223. 11. Catalina-Fernandez I, Lopez-Presa D, Saenz-Santamaria J. Fine needle aspiration cytology in cutaneous and subcutaneous endometriosis. Acta Cytol. 2007;51:380-384. 12. Tumay V, Ozturk E, Ozturk H, et al. Appendiceal endometriosis mimicking acute appendicitis. Acta Chir Belg. 2006;106:712713. 13. Dones J, Spada F, Squifflet J, et al. Bladder endometriosis must be considered as bladder adenomyosis. Fertil Steril. 2000;74:1175-1181. 14. Fujita K. Endometriosis of the ureter. J Urol. 1976;116:664-666. 15. Chapron C. Doleur et endometriose profonde. J Gynecol Biol Reprod 2003;32:32-36.
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