Int Urogynecol J DOI 10.1007/s00192-015-2665-1
REVIEW ARTICLE
Urinary retention and uterine leiomyomas: a case series and systematic review of the literature Clara Q. Wu & Guylaine Lefebvre & Helena Frecker & Heinrich Husslein
Received: 18 November 2014 / Accepted: 17 February 2015 # The International Urogynecological Association 2015
Abstract Uterine leiomyomas are underrecognized as a cause of acute urinary retention (AUR) in women. The objective of this study was to present a case series and systematic review of the literature, to elucidate the pathogenesis of leiomyoma-related AUR, and to suggest management strategies. We included patients presenting with AUR and uterine leiomyomas at our institution between January 2011 and December 2013. Further, we systematically searched the Cochrane Library (from 1898 to June 2014), EMBASE (from 1947 to June 2014), and MEDLINE (from 1946 to June 2014) databases according to the PRISMA guidelines. A total of six patients with AUR and leiomyomas presented to our institution. Through the systematic review, another 31 cases of AUR were identified. Combined patient ages ranged from 25 to 75 years. Uterine size ranged from 10 to 22 weeks on physical examination and from 5.5 to 26 cm on imaging. The dominant leiomyoma size ranged from 5.7 to 22.4 cm. Significant risk factors were posterior or fundal leiomyoma position and the presence of a retroverted uterus. Proposed mechanisms for leiomyoma-related AUR include proximal urethra or
bladder-neck compression, premenstrual pelvic congestion, vascular steal effect, and compression of pudendal or sacral nerves. Patients were treated with hysterectomy, myomectomy, uterine fibroid embolization, hormones, or by conservative management alone. In the absence of neurologic disorders or other risk factors, neither urodynamic studies nor neuromuscular testing seem to contribute to diagnosis or guide management in women with uterine leiomyomas and AUR. Patients presenting to gynecologists seem to experience shorter times to diagnosis and treatment compared with other specialties. It is essential to recognize leiomyomas as a potential cause of AUR in order to reduce unnecessary testing and delays in diagnosis and management. Keywords Acute urinary retention . Fibroid-induced retention . Uterine leiomyomas . Urinary obstruction
Introduction
Electronic supplementary material The online version of this article (doi:10.1007/s00192-015-2665-1) contains supplementary material, which is available to authorized users. C. Q. Wu Department of Obstetrics, Gynecology & Reproductive Sciences, University of Saskatchewan, Regina, Saskatchewan, Canada G. Lefebvre : H. Frecker : H. Husslein Division of Obstetrics and Gynecology, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada H. Husslein (*) Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria e-mail: [email protected]
Acute urinary retention (AUR) is a rare condition in women, with an incidence of approximately 7:100,000 per year [1, 2]. AUR can be a result of impaired detrusor contractility or mechanical obstruction [3]. Common causes include neurogenic insult (multiple sclerosis, spinal-cord injury, diabetes), constipation, medications, infections, stones, tumors, and psychogenic etiologies [4, 5]. The incidence of urinary retention in reproductive-aged women has been estimated to be around 3:100,000 [6]. Gynecology-associated cases of AUR involve mostly postoperative patients [7, 8] but can also be related to benign or malignant pelvic tumors, pelvic organ prolapse, postpartum vulvar edema, labial fusion, and imperforate hymen [5, 9]. Generally, affected patients experience variable difficulties with bladder emptying, followed by intermittent
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and subsequently recurrent episodes of AUR. In some instances, sudden onset of AUR without precursor symptoms can occur. Duration of AUR episodes may vary, and spontaneous resolution may occur. Nevertheless, bladder decompression via catheterization is often required [4]. Uterine leiomyomas are the most common type of tumors found in women [10]. It is estimated that 30 % of reproductive-age women have uterine leiomyomas, and of those, 25 % are symptomatic [11]. There has been little published evidence relating AUR to uterine leiomyomas, and current guidelines do not provide specific recommendations on the management of AUR in this condition [10, 12–14]. Published articles are case reports and case series, with no retrospective or prospective controlled studies on the topic. Despite more than three decades since the first published case report, we continue to lack concrete understanding of the pathophysiological mechanisms underlying AUR in women with uterine leiomyomas. The objective of this study was to present a series of AUR cases in patients with uterine leiomyomas and to perform a systematic review of the literature to identify salient case reports of AUR and to provide the most comprehensive and up to date review on the topic. We attempt to summarize the currently available evidence regarding the pathogenesis of AUR in the context of uterine leiomyomas and provide guidance in the management of AUR in such patients.
Methods
through the St. Michael’s Hospital Medical Records Database (Soarian Clinicals, Siemens Medical Solutions USA, Inc). The study was conducted following approval from the St. Michael’s Hospital Research Ethics Board (REB# 14238c). Systematic review We systematically searched the Cochrane Library (from 1898 to June 2014), EMBASE (from 1947 to June 2014), and MEDLINE (from 1946 to June 2014) databases. The search strategy was devised in collaboration with a research librarian. Search terms used included Burinary retention^, Bfibroid^, Bl e i o m y o m a ^, a n d But er in e m yo ma ^ (s ee Onl ine Appendix A). We retrieved all English-language publications examining urinary retention in women with uterine leiomyoma. All citations were first screened by two independent reviewers in duplicate. Selected studies were then assessed on a full-text level. Disparities were resolved with group discussion. Studies examining urinary retention in women with gravid uteri, nonuterine leiomyomas, or neurological disorders were excluded. Review articles, letters, and editorials were equally excluded (Fig. 1). Data involving patient characteristics, clinical presentation, physical examination, imaging results, treatment modality, pathology reports, and treatment outcome were retrieved by the two independent researchers using an electronic data extraction form and analyzed in light of results of our case series. This systematic review was performed in accordance with the PRISMA statement guidelines [15].
Case series We conducted a chart review of patients who were treated for episodes of AUR and uterine leiomyoma at St. Michael’s Hospital in Toronto, Canada, from January 2011 to December 2013 inclusively. Patients were selected from the operative lists of the Minimally-Invasive Surgery Staff at the Department of Obstetrics and Gynecology. All patients with the dual diagnosis of AUR and uterine leiomyoma were selected for inclusion. Patients were excluded from the study if they had a gravid uterus, urinary disorders, stones, tumors, or psychogenic conditions susceptible to causing AUR. Patients’ surgical records relating to their gynecological surgery for uterine leiomyoma during the study period were reviewed. The following demographic and clinical data were abstracted from individual patient charts: age, gravity, parity, smoking status, previous medical history, clinical presentation of AUR, body mass index (BMI), physical exam findings, imaging results [ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI)], and pathology report. Intervention method [surgery, uterine fibroid embolization (UFE), medical or conservative therapy] and postoperative outcomes were also abstracted. Patient data were retrieved
Results Case series We screened the operative lists of the Minimally-Invasive Surgery Staff at our Department of Obstetrics and Gynecology and retrieved medical records of 568 consecutive women who had either been seen in consultation for or had undergone a hysterectomy or myomectomy in our hospital by laparotomy, laparoscopy, hysteroscopy, or robotic surgery. Of those, 284 cases were performed for uterine leiomyomas. After application of inclusion and exclusion criteria, six patients with the dual diagnosis of AUR and uterine leiomyomas were identified (Table 1). Patient ages ranged between 38 and 51 years. All except one patient were parous (83.3 %). All patients were premenopausal (2/6; 33.3 %) or perimenopausal (4/6; 66.7 %). BMI ranged between 21.6 and 34.4 kg/m2. All except one patient had recurrent episodes of AUR. Urinary frequency, urgency, stress urinary incontinence, pressure, and difficulty initiating flow were among other associated symptoms presented in our case series. Of note, patient 4
Int Urogynecol J Fig. 1 Literature review process
Articles identified through the Cochrane Library (n = 11)
Articles identified through EMBASE (n = 90)
Articles identified through MEDLINE (n = 57)
Articles identified through database searching (n = 158)
Additional articles identified through search of the grey literature (n = 0)
Articles after duplicates removed (n = 117)
Articles screened (n = 117)
Full-text articles assessed for eligibility (n = 20)
Articles excluded (n = 97) - Not relevant (n = 91) - Review articles (n = 3) - Letter/commentary (n = 2) - Abstract only (n = 1)
Full-text articles excluded (n = 0) Studies included in qualitative synthesis (n = 20)
had a history of multiple sclerosis; at the time of presentation, she was asymptomatic and had an expanded disability status scale score of zero. On physical examination, all patients had enlarged uteri, ranging from 10 to 22 weeks in size. Four patients had a retroverted uterus, one of which had documented anterior cervical deviation; one had an anteverted uterus; one case did not report on uterus position. Based on imaging results, uterine size measured between 5.5×5.7 cm and 22.4×14.1×10.5 cm. The dominant leiomyomas ranged between 5.9×7.6×7.8 and 13.6×12.2×7.8 cm in size and were varied in location (2 posterior, 1 fundal, 1 central, and 1 anterior). Two patients were treated via vaginal hysterectomy, one with abdominal hysterectomy, one with laparoscopicassisted vaginal hysterectomy, one with total laparoscopic hysterectomy, and one with ulipristal acetate. AUR symptoms resolved in all patients following treatment. On pathology, uteri weighed between 421 and 998 g. Time from AUR onset to diagnosis varied between 6 and 78 months. Systematic review Our systematic search of the literature yielded 158 studies across three databases (Fig. 1). After removal of duplicates, 117 titles and abstracts were screened for potentially relevant articles for inclusion. Articles unrelated to the correlation between AUR and uterine leiomyomas (n=91), review articles
(n=3), letters and editorials (n=2), and abstract-only articles (n=1) were subsequently excluded. Ultimately, 20 studies met inclusion criteria and were reviewed in full length. Twenty studies (16 case reports and 4 case series totaling 31 women) are included in this systematic review (for a detailed description of each case, please see Online Appendix B). Case reports were published between 1978 and 2014 and originated from Belgium, Greece, India, Japan, Spain, Taiwan, Turkey, and the United States. Patient age ranged from 25 to 53 years. All women had confirmed uterine leiomyomas and presented with either new-onset or recurrent AUR. AUR was commonly accompanied by other obstructive urinary symptoms, such as difficulty emptying, pelvic pressure, and recurrent urinary tract infections. On physical examination, patients had reportedly 14- to 20week-size uteri, and the majority had a posterior mass occupying or impacting into the pelvic cul-de-sac. Diagnostic and imaging reports included pelvic US, MRI, CT, urodynamic studies, needle electromyography, and cystourethroscopy. Uterine size ranged between 8.0×9.6×9.9 and 20.2×16.8× 12.8 cm, with a dominant leiomyoma size between 5.7×4.3 and 11×11.6×11.7 cm. Based on the 18 cases that reported on dominant leiomyoma positions, nine leiomyomas were posterior [7, 13, 16–21], five fundal [13, 22], two central [13, 14], one anterior [23], and two in the lower body of the uterus [23, 24].
46
53
42
38
45
51
1
2
3
4
5
6
5
2
3
2
0
2
G
2
1
1
2
0
2
P
NR
34.4
25.1
31.7
21.6
25.9
BMI
Recurrent AUR, urinary frequency, urgency, stress incontinence, pressure, difficulty initiating flow
Recurrent AUR, stress incontinence Single episode AUR, urinary frequency
Recurrent AUR, urinary frequency
Recurrent AUR, urinary frequency
Recurrent AUR (2–3×/month)× 13 months, feeling of protrusion from the vaginal introitus
Symptom presentation
US: 22.4×14.1×10.5 cm anteverted uterus; 13.6×12.2×7.8 cm submucosal central fibroid MRI: 6.6×7.7×16 cm retroverted, multifibroid uterus; 6.3×8.2×9.1 cm intramural fibroid in anterior lower uterine body
US: retroverted, multifibroid uterus; 7 cm fibroid in the posterior aspect of the lower uterine segment US: 10.8 cm retroverted, immobile uterus; 10.4×9.7×9.3 cm intramural posterior fibroid US: 5.7×5.5 cm retroverted uterus; 7.8×7.6×5.9 cm subserosal fundal fibroid NR
Diagnostic findings
Ulipristal acetate
Vaginal hysterectomy, McCall culdoplasty Total laparoscopic hysterectomy
Abdominal hysterectomy
Vaginal hysterectomy, McCall culdoplasty
Laparoscopic assisted vaginal hysterectomy, McCall culdoplasty
Treatment
NA
998 g uterus
458 g uterus
970 g uterus
421 g uterus
535 g uterus
Pathology
AUR acute urinary retention, G gravidity, P parity, BMI body mass index, MRI magnetic resonance imaging, NA not applicable, NR not reported, US ultrasound
Age
Patients with urinary retention and uterine leiomyoma
Case no.
Table 1
NR
78
NR
18
6
13
Time from symptom onset to diagnosis (months)
Immediate postoperative resolution
Immediate postoperative resolution Immediate postoperative resolution
Immediate postoperative resolution
Immediate postoperative resolution
Immediate postoperative resolution
Outcome
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Twenty patients (64.5 %) were treated with hysterectomy by laparotomy or laparoscopy with or without oophorectomy [3, 7, 12, 13, 16–20, 25–29]. The others were treated by uterine-sparing procedures, specifically, four by myomectomy [13, 22, 24], three with UFE [23, 30], two with lifestyle modifications [12], one with a ganodotropin-releasing hormone (GnRH) antagonist (depot leuprolide acetate) [14], and one with an aromatase inhibitor (fadrazole) [21]. On pathology, uteri weighed between 330 and 2,750 g. Patients waited on average 7 months (from 2 weeks to 2 years) before receiving a diagnosis. Symptoms of AUR resolved in all patients following treatment(s). Combined cases The results from our case series are in accordance with our findings from the literature. Notably, AUR only occurred in patients with a dominant leiomyoma size >5 cm. Upon combining our case series with the cases from the literature, 37 women with AUR were evaluated. Patient ages ranged from 25 to 75 years. Uterine size ranged from 10 to 22 weeks on physical examination and from 5.5 to 26 cm on imaging. The dominant leiomyoma size ranged from 5.7 to 22.4 cm; with regard to location, 11 were posterior, six fundal, three central, two anterior, and two in the lower body of the uterus. Pathological examination revealed the uterine weight to be between 330 and 2,750 g.
Discussion Results of our systematic review of the literature demonstrate that there is only limited evidence regarding uterine leiomyomas and AUR. Generally, affected patients may either present with a sudden onset of AUR without precursor symptoms or experience variable difficulties with bladder emptying, culminating in intermittent and subsequently recurrent episodes of AUR of variable duration. Several mechanisms have been proposed by which uterine leiomyomas can cause AUR. The most commonly reported hypothesis suggests that an impacted fibroid uterus causes proximal urethral or bladder-neck compression by anterior and superior deviation of the cervix [7, 12, 16, 17, 22]. During normal physiologic voiding, the cervix is rotated away from the urethra and/or bladder neck, which may be hindered by uterine leiomyomas. Some authors postulate that rather than direct compression of the urethra, the anterior and superior displacement of the cervix leads to compression of the lower portion of the bladder. Collapse of the lower bladder, which is more likely in when the patient is in the supine position, then interferes with urine drainage into the urethra and results in AUR [12, 26, 31].
Hormonal factors can further aggravate the compressive symptoms. It is speculated that premenstrual pelvic congestion may aggravate leiomyoma-related anatomical distortions [25]. We were, however, unable to verify this theory with our case series, as we did not have symptom calendars in relation to women’s menstrual cycles. In addition, the premenstrual surge in prostaglandin synthesis and the lowered uterine artery impendence are reported to increase intrauterine pressure and uterine volume [7, 25]. Furthermore, highly vascularized fibroids may appropriate blood supply from the surrounding pelvic organs (i.e., the vascular steal effect), thereby creating a state of relative chronic hypoxia of the surrounding organs [30]. Chronic ischemia has been shown to damage detrusor contractility in animal studies [32, 33]. This hypothesis is bolstered by reports of UFE resolving AUR [30]. It has been suggested that it is not the volume reduction and subsequent relief of mechanical obstruction that corrects AUR but, rather, the reduction in perfusion within the leiomyoma. Lastly, it has been proposed that an impacted fibroid uterus may compress the pudendal and sacral nerves, thus impeding bladder-muscle innervation [20]. Andrada et al. conducted urodynamic testing and needle electromyography in women with fibroids and AUR, confirming a neurogenic lesion compatible with chronic motor polyradiculopathy of S1 and S2 nerve roots, along with an acontractile detrusor muscle [20]. The authors hypothesized that the leiomyomas compressed the pelvic plexus, thus inducing axonal loss in muscles innervated by S1 and S2 nerve roots. Surprisingly, the electromyogram normalized 4 months after abdominal hysterectomy. In summary, the development of AUR in patients with uterine leiomyomas seems to be dependent on anatomical and hormonal factors as well as factors related to leiomyoma size and location. The critical size at which symptoms of AUR develop is dependent on individual anatomical variation and distortion, but a dominant uterine leiomyoma size of 5–6 cm seems to be necessary to cause AUR. Leiomyomas located in the posterior or fundal aspect of the uterus and which are associated with a retroverted uterus seem to pose the greatest risk based on our series and review of available evidence. However, data about the location of leiomyomas in the general population is lacking, therefore it is unclear whether the location of fibroids is really a risk factor or just mirrors the general distribution. Impaction or incarceration of a leiomyoma or the uterus in the hollow of the sacrum seems to be a critical factor for the development of AUR in the majority of cases. The incarceration process is likely of greater importance than the actual size of the dominant leiomyoma or uterus. Often, very large uterine leiomyomas or uteri do not cause AUR; they surpass the sacral promontory and can grow freely without entrapment into the hollow of the sacrum. Current practice guidelines on the management of uterine leiomyomas do not specify the treatment of urinary retention in these patients [10]. Authors of existing literature advocate for the acute management of AUR with bladder decompression through catheterization, either with an indwelling French
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Foley catheter, a suprapubic catheter, or clean intermittent catheterization [34], until further treatment can be undertaken [4, 26]. Additional conservative management strategies include limiting fluid intake before sleep, changing position from supine to prone before getting up, leaning forward when initiating voids, avoiding straining, using the Credé maneuver to void, and a trial of a pessary to elevate the bladder neck [12, 13]. Of note, patients identified in our combined case series waited between 2 and 78 months before diagnosis of the cause of their AUR could be confirmed. Yazdany et al. related that patients presenting to the urology department underwent surgical intervention on average 14 months after first presentation for treatment of the cause of AUR, whereas gynecology patients waited 2.1 months. Indeed, since uterine leiomyomas are not yet a well-established cause of AUR, patients often experience unnecessary testing and delays in intervention and treatment [13]. If left untreated, AUR can cause permanent damage to the detrusor muscle, development of bladder trabeculation, diverticula, vesicoureteral reflux, and recurrent urinary tract infections [19, 35]. In the absence of neurologic disorders or other risk factors (e.g., constipation, medications, etc.), neither urodynamic studies nor neuromuscular testing seem to contribute to the diagnosis or to guiding treatment management in women with uterine leiomyomas and AUR [12, 20, 26]. Regarding surgical treatment options, hysterectomy is the most definitive management for AUR patients with uterine
leiomyomas. Uterus-preserving options include myomectomy and UFE, although recurrence of AUR after UFE has been reported [13, 23, 36, 37]. The minimally invasive approach in our series distinguishes itself from the abdominal approach reported in most cases in the literature. For perimenopausal patients, a trial of GnRH agonist, aromatase inhibitor, or ulipristal acetate may be considered prior to surgical treatment [11, 21, 38, 39]. We report the incipient use of ulipristal acetate use for AUR in patients with uterine leiomyomas (see case 6). Ulipristal acetate is a selective progesterone receptor modulator (SPRM) with proapoptotic and antiproliferative effects on leiomyoma cells. Its use has effectively reduced fibroid size in previous studies [40–42]. Ultimately, treatment options depend on the clinical situation, patient preference, and individualized risk–benefit evaluation. A proposed algorithm for the management of AUR in women with uterine leiomyomas is shown in Fig. 2. In order to establish a better understanding of the pathophysiology of AUR in women with uterine leiomyomas, including the effect of specific combinations of anatomical features and leiomyoma/uterine size and location, prospective controlled studies should be conducted. However, given the difficulty in powering prospective studies for a rare event such as AUR, a retrospective analysis may be the most feasible method by which to review this topic. Our study summarizes the best available evidence on this topic regarding pathophysiological hypotheses and treatment options. For physicians
AUR in a female patient
Physical and pelvic exam, urine sample and TVUS +/- MRI
Absence of leiomyoma
Consider other DDx for AUR
Presence of leiomyoma
Other risk factors for AUR present (i.e. neurological disorders, etc.)
Additional investigations only if clinically indicated
Short-term management Bladder decompression through catheterization
Abbreviations: AUR = acute urinary retention. DDx = differential diagnoses. GnRH = gonadotropin releasing hormone. MRI = magnetic resonance imaging. TVUS = transvaginal ultrasound. UFE = uterine fibroid embolization.
Fig. 2 Management of leiomyoma-related acute urinary retention
5-6cm
Long-term management
Behavioral changes in women denying surgery or hormonal treatment
Fertility no longer desired
Menopausal
Pre/perimenopausal
Hysterectomy
Hysterectomy, UFE, GnRH agonists, aromatase inhibitor, ulipristal acetate
Fertility desired Myomectomy, GnRH agonists, aromatase inhibitor, ulipristal acetate
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confronted with women with AUR, it is essential to recognize uterine leiomyomas as a potential cause in order to reduce unnecessary testing and avoid delays in diagnosis and management.
Funding This study did not receive external funding. Conflicts of interest None Author contribution Wu: Project development, data collection, and manuscript writing Lefebvre: Project development, and manuscript writing and editing Frecker: Data collection, and manuscript writing and editing Husslein: Project development, data collection, and manuscript writing and editing
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REVIEW ARTICLE
Urinary retention and uterine leiomyomas: a case series and systematic review of the literature Clara Q. Wu & Guylaine Lefebvre & Helena Frecker & Heinrich Husslein
Received: 18 November 2014 / Accepted: 17 February 2015 # The International Urogynecological Association 2015
Abstract Uterine leiomyomas are underrecognized as a cause of acute urinary retention (AUR) in women. The objective of this study was to present a case series and systematic review of the literature, to elucidate the pathogenesis of leiomyoma-related AUR, and to suggest management strategies. We included patients presenting with AUR and uterine leiomyomas at our institution between January 2011 and December 2013. Further, we systematically searched the Cochrane Library (from 1898 to June 2014), EMBASE (from 1947 to June 2014), and MEDLINE (from 1946 to June 2014) databases according to the PRISMA guidelines. A total of six patients with AUR and leiomyomas presented to our institution. Through the systematic review, another 31 cases of AUR were identified. Combined patient ages ranged from 25 to 75 years. Uterine size ranged from 10 to 22 weeks on physical examination and from 5.5 to 26 cm on imaging. The dominant leiomyoma size ranged from 5.7 to 22.4 cm. Significant risk factors were posterior or fundal leiomyoma position and the presence of a retroverted uterus. Proposed mechanisms for leiomyoma-related AUR include proximal urethra or
bladder-neck compression, premenstrual pelvic congestion, vascular steal effect, and compression of pudendal or sacral nerves. Patients were treated with hysterectomy, myomectomy, uterine fibroid embolization, hormones, or by conservative management alone. In the absence of neurologic disorders or other risk factors, neither urodynamic studies nor neuromuscular testing seem to contribute to diagnosis or guide management in women with uterine leiomyomas and AUR. Patients presenting to gynecologists seem to experience shorter times to diagnosis and treatment compared with other specialties. It is essential to recognize leiomyomas as a potential cause of AUR in order to reduce unnecessary testing and delays in diagnosis and management. Keywords Acute urinary retention . Fibroid-induced retention . Uterine leiomyomas . Urinary obstruction
Introduction
Electronic supplementary material The online version of this article (doi:10.1007/s00192-015-2665-1) contains supplementary material, which is available to authorized users. C. Q. Wu Department of Obstetrics, Gynecology & Reproductive Sciences, University of Saskatchewan, Regina, Saskatchewan, Canada G. Lefebvre : H. Frecker : H. Husslein Division of Obstetrics and Gynecology, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada H. Husslein (*) Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria e-mail: [email protected]
Acute urinary retention (AUR) is a rare condition in women, with an incidence of approximately 7:100,000 per year [1, 2]. AUR can be a result of impaired detrusor contractility or mechanical obstruction [3]. Common causes include neurogenic insult (multiple sclerosis, spinal-cord injury, diabetes), constipation, medications, infections, stones, tumors, and psychogenic etiologies [4, 5]. The incidence of urinary retention in reproductive-aged women has been estimated to be around 3:100,000 [6]. Gynecology-associated cases of AUR involve mostly postoperative patients [7, 8] but can also be related to benign or malignant pelvic tumors, pelvic organ prolapse, postpartum vulvar edema, labial fusion, and imperforate hymen [5, 9]. Generally, affected patients experience variable difficulties with bladder emptying, followed by intermittent
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and subsequently recurrent episodes of AUR. In some instances, sudden onset of AUR without precursor symptoms can occur. Duration of AUR episodes may vary, and spontaneous resolution may occur. Nevertheless, bladder decompression via catheterization is often required [4]. Uterine leiomyomas are the most common type of tumors found in women [10]. It is estimated that 30 % of reproductive-age women have uterine leiomyomas, and of those, 25 % are symptomatic [11]. There has been little published evidence relating AUR to uterine leiomyomas, and current guidelines do not provide specific recommendations on the management of AUR in this condition [10, 12–14]. Published articles are case reports and case series, with no retrospective or prospective controlled studies on the topic. Despite more than three decades since the first published case report, we continue to lack concrete understanding of the pathophysiological mechanisms underlying AUR in women with uterine leiomyomas. The objective of this study was to present a series of AUR cases in patients with uterine leiomyomas and to perform a systematic review of the literature to identify salient case reports of AUR and to provide the most comprehensive and up to date review on the topic. We attempt to summarize the currently available evidence regarding the pathogenesis of AUR in the context of uterine leiomyomas and provide guidance in the management of AUR in such patients.
Methods
through the St. Michael’s Hospital Medical Records Database (Soarian Clinicals, Siemens Medical Solutions USA, Inc). The study was conducted following approval from the St. Michael’s Hospital Research Ethics Board (REB# 14238c). Systematic review We systematically searched the Cochrane Library (from 1898 to June 2014), EMBASE (from 1947 to June 2014), and MEDLINE (from 1946 to June 2014) databases. The search strategy was devised in collaboration with a research librarian. Search terms used included Burinary retention^, Bfibroid^, Bl e i o m y o m a ^, a n d But er in e m yo ma ^ (s ee Onl ine Appendix A). We retrieved all English-language publications examining urinary retention in women with uterine leiomyoma. All citations were first screened by two independent reviewers in duplicate. Selected studies were then assessed on a full-text level. Disparities were resolved with group discussion. Studies examining urinary retention in women with gravid uteri, nonuterine leiomyomas, or neurological disorders were excluded. Review articles, letters, and editorials were equally excluded (Fig. 1). Data involving patient characteristics, clinical presentation, physical examination, imaging results, treatment modality, pathology reports, and treatment outcome were retrieved by the two independent researchers using an electronic data extraction form and analyzed in light of results of our case series. This systematic review was performed in accordance with the PRISMA statement guidelines [15].
Case series We conducted a chart review of patients who were treated for episodes of AUR and uterine leiomyoma at St. Michael’s Hospital in Toronto, Canada, from January 2011 to December 2013 inclusively. Patients were selected from the operative lists of the Minimally-Invasive Surgery Staff at the Department of Obstetrics and Gynecology. All patients with the dual diagnosis of AUR and uterine leiomyoma were selected for inclusion. Patients were excluded from the study if they had a gravid uterus, urinary disorders, stones, tumors, or psychogenic conditions susceptible to causing AUR. Patients’ surgical records relating to their gynecological surgery for uterine leiomyoma during the study period were reviewed. The following demographic and clinical data were abstracted from individual patient charts: age, gravity, parity, smoking status, previous medical history, clinical presentation of AUR, body mass index (BMI), physical exam findings, imaging results [ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI)], and pathology report. Intervention method [surgery, uterine fibroid embolization (UFE), medical or conservative therapy] and postoperative outcomes were also abstracted. Patient data were retrieved
Results Case series We screened the operative lists of the Minimally-Invasive Surgery Staff at our Department of Obstetrics and Gynecology and retrieved medical records of 568 consecutive women who had either been seen in consultation for or had undergone a hysterectomy or myomectomy in our hospital by laparotomy, laparoscopy, hysteroscopy, or robotic surgery. Of those, 284 cases were performed for uterine leiomyomas. After application of inclusion and exclusion criteria, six patients with the dual diagnosis of AUR and uterine leiomyomas were identified (Table 1). Patient ages ranged between 38 and 51 years. All except one patient were parous (83.3 %). All patients were premenopausal (2/6; 33.3 %) or perimenopausal (4/6; 66.7 %). BMI ranged between 21.6 and 34.4 kg/m2. All except one patient had recurrent episodes of AUR. Urinary frequency, urgency, stress urinary incontinence, pressure, and difficulty initiating flow were among other associated symptoms presented in our case series. Of note, patient 4
Int Urogynecol J Fig. 1 Literature review process
Articles identified through the Cochrane Library (n = 11)
Articles identified through EMBASE (n = 90)
Articles identified through MEDLINE (n = 57)
Articles identified through database searching (n = 158)
Additional articles identified through search of the grey literature (n = 0)
Articles after duplicates removed (n = 117)
Articles screened (n = 117)
Full-text articles assessed for eligibility (n = 20)
Articles excluded (n = 97) - Not relevant (n = 91) - Review articles (n = 3) - Letter/commentary (n = 2) - Abstract only (n = 1)
Full-text articles excluded (n = 0) Studies included in qualitative synthesis (n = 20)
had a history of multiple sclerosis; at the time of presentation, she was asymptomatic and had an expanded disability status scale score of zero. On physical examination, all patients had enlarged uteri, ranging from 10 to 22 weeks in size. Four patients had a retroverted uterus, one of which had documented anterior cervical deviation; one had an anteverted uterus; one case did not report on uterus position. Based on imaging results, uterine size measured between 5.5×5.7 cm and 22.4×14.1×10.5 cm. The dominant leiomyomas ranged between 5.9×7.6×7.8 and 13.6×12.2×7.8 cm in size and were varied in location (2 posterior, 1 fundal, 1 central, and 1 anterior). Two patients were treated via vaginal hysterectomy, one with abdominal hysterectomy, one with laparoscopicassisted vaginal hysterectomy, one with total laparoscopic hysterectomy, and one with ulipristal acetate. AUR symptoms resolved in all patients following treatment. On pathology, uteri weighed between 421 and 998 g. Time from AUR onset to diagnosis varied between 6 and 78 months. Systematic review Our systematic search of the literature yielded 158 studies across three databases (Fig. 1). After removal of duplicates, 117 titles and abstracts were screened for potentially relevant articles for inclusion. Articles unrelated to the correlation between AUR and uterine leiomyomas (n=91), review articles
(n=3), letters and editorials (n=2), and abstract-only articles (n=1) were subsequently excluded. Ultimately, 20 studies met inclusion criteria and were reviewed in full length. Twenty studies (16 case reports and 4 case series totaling 31 women) are included in this systematic review (for a detailed description of each case, please see Online Appendix B). Case reports were published between 1978 and 2014 and originated from Belgium, Greece, India, Japan, Spain, Taiwan, Turkey, and the United States. Patient age ranged from 25 to 53 years. All women had confirmed uterine leiomyomas and presented with either new-onset or recurrent AUR. AUR was commonly accompanied by other obstructive urinary symptoms, such as difficulty emptying, pelvic pressure, and recurrent urinary tract infections. On physical examination, patients had reportedly 14- to 20week-size uteri, and the majority had a posterior mass occupying or impacting into the pelvic cul-de-sac. Diagnostic and imaging reports included pelvic US, MRI, CT, urodynamic studies, needle electromyography, and cystourethroscopy. Uterine size ranged between 8.0×9.6×9.9 and 20.2×16.8× 12.8 cm, with a dominant leiomyoma size between 5.7×4.3 and 11×11.6×11.7 cm. Based on the 18 cases that reported on dominant leiomyoma positions, nine leiomyomas were posterior [7, 13, 16–21], five fundal [13, 22], two central [13, 14], one anterior [23], and two in the lower body of the uterus [23, 24].
46
53
42
38
45
51
1
2
3
4
5
6
5
2
3
2
0
2
G
2
1
1
2
0
2
P
NR
34.4
25.1
31.7
21.6
25.9
BMI
Recurrent AUR, urinary frequency, urgency, stress incontinence, pressure, difficulty initiating flow
Recurrent AUR, stress incontinence Single episode AUR, urinary frequency
Recurrent AUR, urinary frequency
Recurrent AUR, urinary frequency
Recurrent AUR (2–3×/month)× 13 months, feeling of protrusion from the vaginal introitus
Symptom presentation
US: 22.4×14.1×10.5 cm anteverted uterus; 13.6×12.2×7.8 cm submucosal central fibroid MRI: 6.6×7.7×16 cm retroverted, multifibroid uterus; 6.3×8.2×9.1 cm intramural fibroid in anterior lower uterine body
US: retroverted, multifibroid uterus; 7 cm fibroid in the posterior aspect of the lower uterine segment US: 10.8 cm retroverted, immobile uterus; 10.4×9.7×9.3 cm intramural posterior fibroid US: 5.7×5.5 cm retroverted uterus; 7.8×7.6×5.9 cm subserosal fundal fibroid NR
Diagnostic findings
Ulipristal acetate
Vaginal hysterectomy, McCall culdoplasty Total laparoscopic hysterectomy
Abdominal hysterectomy
Vaginal hysterectomy, McCall culdoplasty
Laparoscopic assisted vaginal hysterectomy, McCall culdoplasty
Treatment
NA
998 g uterus
458 g uterus
970 g uterus
421 g uterus
535 g uterus
Pathology
AUR acute urinary retention, G gravidity, P parity, BMI body mass index, MRI magnetic resonance imaging, NA not applicable, NR not reported, US ultrasound
Age
Patients with urinary retention and uterine leiomyoma
Case no.
Table 1
NR
78
NR
18
6
13
Time from symptom onset to diagnosis (months)
Immediate postoperative resolution
Immediate postoperative resolution Immediate postoperative resolution
Immediate postoperative resolution
Immediate postoperative resolution
Immediate postoperative resolution
Outcome
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Twenty patients (64.5 %) were treated with hysterectomy by laparotomy or laparoscopy with or without oophorectomy [3, 7, 12, 13, 16–20, 25–29]. The others were treated by uterine-sparing procedures, specifically, four by myomectomy [13, 22, 24], three with UFE [23, 30], two with lifestyle modifications [12], one with a ganodotropin-releasing hormone (GnRH) antagonist (depot leuprolide acetate) [14], and one with an aromatase inhibitor (fadrazole) [21]. On pathology, uteri weighed between 330 and 2,750 g. Patients waited on average 7 months (from 2 weeks to 2 years) before receiving a diagnosis. Symptoms of AUR resolved in all patients following treatment(s). Combined cases The results from our case series are in accordance with our findings from the literature. Notably, AUR only occurred in patients with a dominant leiomyoma size >5 cm. Upon combining our case series with the cases from the literature, 37 women with AUR were evaluated. Patient ages ranged from 25 to 75 years. Uterine size ranged from 10 to 22 weeks on physical examination and from 5.5 to 26 cm on imaging. The dominant leiomyoma size ranged from 5.7 to 22.4 cm; with regard to location, 11 were posterior, six fundal, three central, two anterior, and two in the lower body of the uterus. Pathological examination revealed the uterine weight to be between 330 and 2,750 g.
Discussion Results of our systematic review of the literature demonstrate that there is only limited evidence regarding uterine leiomyomas and AUR. Generally, affected patients may either present with a sudden onset of AUR without precursor symptoms or experience variable difficulties with bladder emptying, culminating in intermittent and subsequently recurrent episodes of AUR of variable duration. Several mechanisms have been proposed by which uterine leiomyomas can cause AUR. The most commonly reported hypothesis suggests that an impacted fibroid uterus causes proximal urethral or bladder-neck compression by anterior and superior deviation of the cervix [7, 12, 16, 17, 22]. During normal physiologic voiding, the cervix is rotated away from the urethra and/or bladder neck, which may be hindered by uterine leiomyomas. Some authors postulate that rather than direct compression of the urethra, the anterior and superior displacement of the cervix leads to compression of the lower portion of the bladder. Collapse of the lower bladder, which is more likely in when the patient is in the supine position, then interferes with urine drainage into the urethra and results in AUR [12, 26, 31].
Hormonal factors can further aggravate the compressive symptoms. It is speculated that premenstrual pelvic congestion may aggravate leiomyoma-related anatomical distortions [25]. We were, however, unable to verify this theory with our case series, as we did not have symptom calendars in relation to women’s menstrual cycles. In addition, the premenstrual surge in prostaglandin synthesis and the lowered uterine artery impendence are reported to increase intrauterine pressure and uterine volume [7, 25]. Furthermore, highly vascularized fibroids may appropriate blood supply from the surrounding pelvic organs (i.e., the vascular steal effect), thereby creating a state of relative chronic hypoxia of the surrounding organs [30]. Chronic ischemia has been shown to damage detrusor contractility in animal studies [32, 33]. This hypothesis is bolstered by reports of UFE resolving AUR [30]. It has been suggested that it is not the volume reduction and subsequent relief of mechanical obstruction that corrects AUR but, rather, the reduction in perfusion within the leiomyoma. Lastly, it has been proposed that an impacted fibroid uterus may compress the pudendal and sacral nerves, thus impeding bladder-muscle innervation [20]. Andrada et al. conducted urodynamic testing and needle electromyography in women with fibroids and AUR, confirming a neurogenic lesion compatible with chronic motor polyradiculopathy of S1 and S2 nerve roots, along with an acontractile detrusor muscle [20]. The authors hypothesized that the leiomyomas compressed the pelvic plexus, thus inducing axonal loss in muscles innervated by S1 and S2 nerve roots. Surprisingly, the electromyogram normalized 4 months after abdominal hysterectomy. In summary, the development of AUR in patients with uterine leiomyomas seems to be dependent on anatomical and hormonal factors as well as factors related to leiomyoma size and location. The critical size at which symptoms of AUR develop is dependent on individual anatomical variation and distortion, but a dominant uterine leiomyoma size of 5–6 cm seems to be necessary to cause AUR. Leiomyomas located in the posterior or fundal aspect of the uterus and which are associated with a retroverted uterus seem to pose the greatest risk based on our series and review of available evidence. However, data about the location of leiomyomas in the general population is lacking, therefore it is unclear whether the location of fibroids is really a risk factor or just mirrors the general distribution. Impaction or incarceration of a leiomyoma or the uterus in the hollow of the sacrum seems to be a critical factor for the development of AUR in the majority of cases. The incarceration process is likely of greater importance than the actual size of the dominant leiomyoma or uterus. Often, very large uterine leiomyomas or uteri do not cause AUR; they surpass the sacral promontory and can grow freely without entrapment into the hollow of the sacrum. Current practice guidelines on the management of uterine leiomyomas do not specify the treatment of urinary retention in these patients [10]. Authors of existing literature advocate for the acute management of AUR with bladder decompression through catheterization, either with an indwelling French
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Foley catheter, a suprapubic catheter, or clean intermittent catheterization [34], until further treatment can be undertaken [4, 26]. Additional conservative management strategies include limiting fluid intake before sleep, changing position from supine to prone before getting up, leaning forward when initiating voids, avoiding straining, using the Credé maneuver to void, and a trial of a pessary to elevate the bladder neck [12, 13]. Of note, patients identified in our combined case series waited between 2 and 78 months before diagnosis of the cause of their AUR could be confirmed. Yazdany et al. related that patients presenting to the urology department underwent surgical intervention on average 14 months after first presentation for treatment of the cause of AUR, whereas gynecology patients waited 2.1 months. Indeed, since uterine leiomyomas are not yet a well-established cause of AUR, patients often experience unnecessary testing and delays in intervention and treatment [13]. If left untreated, AUR can cause permanent damage to the detrusor muscle, development of bladder trabeculation, diverticula, vesicoureteral reflux, and recurrent urinary tract infections [19, 35]. In the absence of neurologic disorders or other risk factors (e.g., constipation, medications, etc.), neither urodynamic studies nor neuromuscular testing seem to contribute to the diagnosis or to guiding treatment management in women with uterine leiomyomas and AUR [12, 20, 26]. Regarding surgical treatment options, hysterectomy is the most definitive management for AUR patients with uterine
leiomyomas. Uterus-preserving options include myomectomy and UFE, although recurrence of AUR after UFE has been reported [13, 23, 36, 37]. The minimally invasive approach in our series distinguishes itself from the abdominal approach reported in most cases in the literature. For perimenopausal patients, a trial of GnRH agonist, aromatase inhibitor, or ulipristal acetate may be considered prior to surgical treatment [11, 21, 38, 39]. We report the incipient use of ulipristal acetate use for AUR in patients with uterine leiomyomas (see case 6). Ulipristal acetate is a selective progesterone receptor modulator (SPRM) with proapoptotic and antiproliferative effects on leiomyoma cells. Its use has effectively reduced fibroid size in previous studies [40–42]. Ultimately, treatment options depend on the clinical situation, patient preference, and individualized risk–benefit evaluation. A proposed algorithm for the management of AUR in women with uterine leiomyomas is shown in Fig. 2. In order to establish a better understanding of the pathophysiology of AUR in women with uterine leiomyomas, including the effect of specific combinations of anatomical features and leiomyoma/uterine size and location, prospective controlled studies should be conducted. However, given the difficulty in powering prospective studies for a rare event such as AUR, a retrospective analysis may be the most feasible method by which to review this topic. Our study summarizes the best available evidence on this topic regarding pathophysiological hypotheses and treatment options. For physicians
AUR in a female patient
Physical and pelvic exam, urine sample and TVUS +/- MRI
Absence of leiomyoma
Consider other DDx for AUR
Presence of leiomyoma
Other risk factors for AUR present (i.e. neurological disorders, etc.)
Additional investigations only if clinically indicated
Short-term management Bladder decompression through catheterization
Abbreviations: AUR = acute urinary retention. DDx = differential diagnoses. GnRH = gonadotropin releasing hormone. MRI = magnetic resonance imaging. TVUS = transvaginal ultrasound. UFE = uterine fibroid embolization.
Fig. 2 Management of leiomyoma-related acute urinary retention
5-6cm
Long-term management
Behavioral changes in women denying surgery or hormonal treatment
Fertility no longer desired
Menopausal
Pre/perimenopausal
Hysterectomy
Hysterectomy, UFE, GnRH agonists, aromatase inhibitor, ulipristal acetate
Fertility desired Myomectomy, GnRH agonists, aromatase inhibitor, ulipristal acetate
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confronted with women with AUR, it is essential to recognize uterine leiomyomas as a potential cause in order to reduce unnecessary testing and avoid delays in diagnosis and management.
Funding This study did not receive external funding. Conflicts of interest None Author contribution Wu: Project development, data collection, and manuscript writing Lefebvre: Project development, and manuscript writing and editing Frecker: Data collection, and manuscript writing and editing Husslein: Project development, data collection, and manuscript writing and editing
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