Embolization Therapy: Principles and Clinical Applications, 1 Ed.

Adenomyosis

Paul N. M. Lohle

BACKGROUND

In the pathophysiology of heavy menstrual bleeding (HMB), two groups may be distinguished: HMB based on anatomic or organic abnormalities (fibroids, adenomyosis, clotting disorders) and essential HMB.1 There is relatively little knowledge about the exact pathophysiology of HMB in relation to fibroids, polyps, and adenomyosis.

Adenomyosis, associated with HMB, is a benign invasion of endometrium into the myometrium that results in a diffusely enlarged uterus that microscopically exhibits ectopic nonneoplastic endometrial glands and stroma surrounded by the hypertrophic and hyperplastic myometrium.2 The prevalence of adenomyosis is estimated to be 5% to 8% and up to 40% to 70%.24 This range may be explained by the different study designs, the random testing described in studies, the lack of a gold standard for identifying adenomyosis, and the use of different transvaginal ultrasound (TVUS), magnetic resonance imaging (MRI), and pathologic anatomical criteria for adenomyosis. Adenomyosis has either a focal or diffuse distribution in the uterine wall. Another problem regarding the relation between HMB and adenomyosis is the fact that in 60% to 80% of the cases, the uterus with adenomyosis is accompanied with other pathology, mostly fibroids, sometimes even in large numbers, small and/or large.3 Risk factors for adenomyosis are caesarean section, induced abortion or curettage, multiparity, miscarriage, endometriosis, and smoking.5

The clinical diagnosis of adenomyosis is sometimes difficult because the presenting symptoms overlap with common uterine disorders such as uterine fibroids.4,6 Therefore, adenomyosis is frequently a so-called forgotten diagnosis because of its noncharacteristic clinical appearance.7 Adenomyosis may be the cause of disabling symptoms such as, in particular, HMB; abdominal, pelvic, low back, and heavy menstrual pain, with or without bulk-related symptoms; and fertility issues in premenopausal women.8

The information on the occurrence of uterine adenomyosis varies considerably. The prevalence of adenomyosis in the specimen obtained from hysterectomy is reported between 8.8% and 31%.9,10 With broad criteria for the diagnosis of adenomyosis, a prevalence as high as 70% in women between 40 and 50 years of age is suggested.4 The incidence of adenomyosis in the population at risk is estimated at 8.1% to 16.7%, with symptomatology in approximately two-thirds of women. Of women with clinical manifestations of adenomyosis, about one-fifth are younger than 40 years of age, but most are between 40 and 50 years of age.1113

Imaging of Adenomyosis

The first-line imaging technique, in women with suspected symptomatic adenomyosis, is usually TVUS, which is inexpensive and readily available. Fundamental TVUS signs to diagnose adenomyosis are an increased myometrial echogenicity or linear hyperechoic bands extending deep into the myometrium, indicating the presence of islets of ectopic endometrial tissue; hypoechoic areas in the myometrium compatible with hyperplasia of the muscle tissue surrounding the ectopic tissue; anechoic areas due to glandular dilatation or myometrial cysts; poor definition of the junctional zone; and an enlargement of the uterus with asymmetrical thickening of one of the walls. The presence of at least three of these signs is highly suggestive of adenomyosis.14

Particularly useful both in doubtful TVUS cases and in providing a complete evaluation of the disease with its panoramic views is MRI. The T2 weighted images with contrast-enhanced T1 weighted MRI provide the thickness of the junctional zone, which can be measured reliably; a thickness over 12 mm is considered diagnostic of adenomyosis (Fig. 55.1A). The occurrence of foci of high signal intensity within the myometrium of the uterus forms an additional but not an obligatory criterion (Fig. 55.1B). MRI can label adenomyosis as focal or diffuse and can be repeated in time to assess the effect of treatment. To assess the diagnostic power of MRI versus TVUS in women with adenomyosis, several studies have been conducted and published. A meta-analysis including six diagnostic accuracy studies of high quality compared TVUS and MRI with histologic proven adenomyosis.15 Champaneria et al.15demonstrated that the correct diagnosis of the occurrence of adenomyosis was provided more often with MRI (sensitivity 0.77/specificity 0.89) than with TVUS (sensitivity 0.72/specificity 0.81), although without statistically significant difference. Another meta-analysis with the study of 1,898 women comparing the TVUS results with the histologic outcome of a symptomatic population of women showed similar sensitivity and specificity results as the meta-analysis of Champaneria et al.: TVUS sensitivity 0.83/specificity 0.85.16 In terms of accuracy, TVUS and MRI seem comparable for diagnosing adenomyosis. Regarding diagnostic imaging before uterine artery embolization, TVUS may very well identify fibroids and adenomyosis. Whether additional imaging such as MRI is needed in all cases is debatable. Nevertheless, in daily practice and from personal experience, MRI is less operator-dependent and therefore very useful and often better compared to TVUS in detecting adenomyosis and determining the vascularization and, thus, the infarction grade after embolization. The combination of both modalities in daily practice provides the best accuracy of ±90%.7,17

Treatment Option for Adenomyosis

Conservative Treatment for Adenomyosis

Women with symptomatic adenomyosis may receive medical treatment, which ranges from local treatment with the release of medications by an intrauterine device (IUD) to systemically administered treatment. IUD-released progestogens are used to reduce HMBs in women with adenomyosis. These medications, such as a Mirena coil, cause the decidualization of the endometrium of the uterus and, consequently, atrophic changes to decrease the amount of blood loss in these women with symptomatic adenomyosis.18

Existing medications for systemic administration include gonadotropin-releasing hormone (GnRH) agonists. GnRH agonists induce menopause by reducing the release of pituitary gonadotropins. The levels of estrogen are lowered, producing atrophy and reduced volume of the uterus with reduction of symptoms, because adenomyosis is an estrogen-dependent disease. If the therapy is stopped, the effect is reversible and symptoms will return.19

Surgical Treatment for Adenomyosis

The usual and preferred surgical approach for focal adenomyosis is excision or enucleation, but the kind of therapy is very much dependent on the type of lesion and the degree of myometrial involvement.19The preferred surgical treatment for women with symptomatic adenomyosis and deep involvement of the myometrium is hysterectomy. The different surgical options and techniques for the treatment of symptomatic adenomyosis have their advantages and disadvantages. When hysterectomy is being considered for diffuse adenomyosis, transvaginal access is preferable to transabdominal access due to the lower morbidity and shorter hospital stay of the former. Concerning the complications of transvaginal hysterectomy, a study on two groups of patients with fibroids versus adenomyosis reported a higher risk of lesions to the urinary bladder in patients from the latter group.20 The reason is probably the greater complexity in identifying the vesicovaginal septum due to the presence of adhesions, which is explained by the frequent presence of pelvic adherences and endometriosis accompanying adenomyosis.8 Hysterectomy is regularly indicated as a definitive treatment. Rates of complication after hysterectomy range between 1.5% and 29.3%. Hysterectomy is associated with complications such as blood loss, bowel and general urogenital injury, pain, and infection. The recovery time ranges from 6 to 8 weeks,19,21,22 and health care–related expenses and lost time at work23 render hysterectomy an option associated with high costs.

Magnetic Resonance Imaging–Guided High-Intensity Focused Ultrasound for Adenomyosis

Magnetic resonance imaging–guided high-intensity focused ultrasound (MRI-HIFU) is a noninvasive image-guided technique that facilitates treatment of tumors by thermoablation with ultrasound waves. The applications are still under research. The therapy is entirely guided by MRI, providing therapy planning, monitoring, and visualization of the treatment result. MRI-HIFU has a broad spectrum of applications, including ablation of uterine fibroids.24 The advantage of the noninvasive character of the treatment is that it can be performed on an outpatient basis and that recovery is fast. MRI-HIFU has been used in adenomyosis with varying results. Therefore, although the technique seems to be a useful alternative, further studies are needed to clarify its effective role.25

TECHNIQUE

The gynecologist Ravina and interventional neuroradiologist Merland were the first to report the uterine artery embolization (UAE) treatment for symptomatic uterine fibroids in Paris.26 UAE has emerged as an effective therapy in the treatment of uterine pathology and, in particular, uterine fibroids. The clinical success rate of UAE for uterine fibroids with respect to symptomatic improvement of associated menorrhagia and pelvic pain ranges from 85% to 95% to 80% to 90%.27,28 This minimally invasive therapeutic alternative to surgery is reported to be associated with a high patient satisfaction.2933 There is about 25% chance of failure of symptom control or recurrence after UAE for uterine fibroids at 5-year follow-up.34,35

The most common indication for selective uterine artery angiography is for embolizing symptomatic fibroids. Based on the resemblance of symptoms caused by fibroids and adenomyosis and the positive results after UAE for fibroids, this intervention has been investigated as an option to treat adenomyosis. Successful infarction of symptomatic fibroids with UAE has been obtained in women suffering from focal or diffuse adenomyosis with or without fibroids. The basic principle is selective infarction of the adenomyosis with particulate embolic materials delivered directly into the uterine arteries and/or uterine artery branches toward the adenomatous tissue in the uterus.

On the day of the UAE procedure, patients are prepared with or without intravenous antibiotic prophylaxis, sedation with 2.5 to 5 mg midazolam when required, and a urinary bladder catheter. Concerning the right moment to perform the UAE procedure in women with adenomyosis, Chen et al.36 evaluated UAE during the menstrual cycle in terms of differences in treatment efficacy. Patients were scheduled for UAE during the proliferative or luteal phase of menstruation. Their data showed that the difference in timing of UAE did not have a significant effect on efficacy in the treatment of adenomyosis.36

An applicable and accepted approach of UAE for adenomyosis is the bilateral UAE carried out after establishing arterial access to the common femoral artery. Selective catheterization of both uterine arteries is performed under fluoroscopic imaging. Bilateral embolization is mandatory. This is usually accomplished by a femoral artery puncture on one side followed by contralateral uterine artery catheterization and after the Waltman loop maneuver embolization of the ipsilateral uterine artery (Fig. 55.2). One may also favor a puncture of both femoral arteries, selecting the ipsilateral internal iliac artery with a recurved “hockey stick–like” catheter.

The UAE catheterization technique for symptomatic adenomyosis is in principle no different from the technique for symptomatic fibroids, apart maybe from the angiographic embolization end point and maybe the embolic agent size. It is reported by some authors that the angiographic embolization end point should be complete stasis at the level of the ascending distal part of both uterine arteries in case of adenomyosis.37,38

When performing UAE, the uterine arteries can be catheterized using a hydrophilic Terumo guidewire with a short-angled tip (Terumo, Tokyo, Japan) and an angled 5-Fr catheter (such as a catheter with a Cobra-2 configuration), but spasm can be a problem so 4-Fr hydrophilic catheters or even 3-Fr microcatheters may be necessary. Once the tip of the (micro)catheter has a stable position in the horizontal part of the uterine artery, a diagnostic angiographic image is obtained. Some experienced interventional radiologists claim to know when dealing with adenomyosis based on the diagnostic angiographic vessel pattern of the uterine branches (Fig. 55.3). Once the “free-flow situation for embolization” with the catheter tip in the horizontal part of the uterine artery is secured, a small syringe containing the embolic material mixed with contrast is attached to the catheter. The embolic agent is administered and gently injected through the catheter into the uterine artery, creating a blockage of the uterine artery branches toward the adenomatous tissue.

The angiographic end point of embolization is the elimination of the adenomatous tissue blush with complete stasis of flow of contrast at the distal end of the ascending segment of both uterine arteries. The stability of the end point is regularly checked after 5 minutes and additional particles injected if the end point is not reached. In the author’s experience, a somewhat more aggressive embolization until complete stasis of contrast at the distal end of the ascending segment of both uterine arteries in women with adenomyosis (as opposed to fibroids) provides better infarction rates and durable clinical results. This is in contrast to the angiographic end point of embolization until near stasis, which seems to be sufficient for treating symptomatic fibroids.34

Failures can be due to incomplete embolization, when the operator fails to catheterize both uterine arteries, or vasospasm of the uterine arteries causing no free-flow embolization; clumping of embolic material; no proper embolization end point; or collateral supply from the ovarian or accessory uterine arteries (Fig. 55.4).

After UAE, patients experience severe pelvic cramping for 12 to 24 hours, followed by gradually decreasing cramping for about 7 days. Approximately 80% of the patients suffer from postembolization syndrome, which includes pain, fever, nausea and/or vomiting, and leukocytosis lasting for a few hours or a few days. Therefore, during and after embolization, intravenous narcotics (with or without the use of a patient-controlled analgesia [PCA] pump) and nonsteroidal anti-inflammatory drugs are administered for adequate pain control and to reduce the previously mentioned symptoms.39 Most patients are managed overnight in the hospital for pain but can be sent home the next day with oral pain medication for 2 weeks. Severe complications are rare (permanent amenorrhea 2% to 5%, expulsion of a coexisting uterine fibroid <2%, sepsis <1%, emergent hysterectomy <1%, death <1%), but uterine infection may require hysterectomy. Young patients who suffer from adenomyosis who desire pregnancy should be properly counselled that there is an incidence of at least 2% to 5% of premature menopause, that is, ovarian failure causing permanent amenorrhea and infertility. Fluoroscopy should be kept to a minimum in all cases, especially in young women. Simultaneous UAE, that is, embolization of both uterine arteries at the same time, reduces the radiation dosage and, in particular, the radiation exposure to the ovaries.

EMBOLIC AGENT

The choice of embolic material is a matter of operator preference, but permanent particulate embolic materials are generally used. Coil occlusion of the uterine artery is not necessary and actually discouraged. The most widely used embolic agent is nonspherical polyvinyl alcohol (PVA) particles ranging from 255 to 900 µm in size.40 Examples of nonspherical PVA particles are Contour (Boston Scientific Corporation, Natick, Massachusetts) and Ivalon (Cook Medical, Inc., Bloomington, Indiana). More recently, however, more and more interventional radiologists prefer the use of spherical embolics, the calibrated microspheres (the preferred size 500 or 700 µm), to facilitate deep penetration into the small afferent arterioles of adenomyosis, creating enough deep infarction (Fig. 55.5). Examples of spherical calibrated microspheres are Embozene (CeloNova BioSciences, Inc., San Antonio, Texas), Embosphere (Merit Medical Systems, Inc., South Jordan, Utah), Contour SE (Boston Scientific Corporation, Natick, Massachusetts), and Bead Block microspheres (Biocompatibles, Inc., Oxford, Connecticutt). In contrast to the perifibroid vascularization pattern of uterine fibroids, adenomyosis has a deep and more diffuse distribution of parallel afferent arterioles throughout the myometrium. The difference in vascularization might explain the reports in the past of higher failure rates in women with adenomyosis compared to UAE for fibroids.

The currently available data do not seem to indicate a preferred embolic agent for use in women with symptomatic adenomyosis. Although in part based on speculation and the author’s experience, deep penetration with the embolic agent seems to be needed for optimal infarction of areas with adenomyosis. Calibrated microspheres are able to selectively occlude the tiny arterial branches of the adenomatous tissue deep in the uterine stroma and thus create adequate tissue infarction. It has been demonstrated that calibrated microspheres have a more predictable behavior. Their uniform size and shape and their constant compressibility and elasticity result in deeper penetration into the small arterioles than nonspherical PVA particles.37,38,41

OUTCOMES

Many studies have documented the treatment of adenomyosis with UAE.3739,4249 Although the first results of UAE for adenomyosis were disappointing, later reports showed significant clinical improvement in most of the treated women with adenomyosis.

To this day, however, there is no randomized controlled trial (RCT) assessing the efficacy of UAE for adenomyosis in comparison to surgery or other treatment options. Although there are critical commentaries by physicians on the published data available,50 the current facts with level 2 evidence demonstrate that UAE for symptomatic adenomyosis is an attractive, sensible, and valuable treatment option.

A meta-analysis has been published on UAE for the treatment of adenomyosis, including 15 studies with a total of 511 patients, published between 1999 and 2010.40 Clinical improvement of bleeding, pain, and bulk-related symptoms were reported by three-quarters of included women with a median follow-up of 26.9 months. In this review, a distinction was made between pure adenomyosis and adenomyosis with uterine fibroids and short-, mid-, and long-term results were described (Table 55.1). Short-term follow-up after UAE in pure adenomyosis resulted in improvement of symptoms in 83% of women with a median follow-up of 9.4 months. The uterine volumes decreased by 25% to 32%. Mid- and long-term results, after a median follow-up of 40.6 months, showed sustained improvement in the vast majority. The short-term results in patients with adenomyosis and fibroids demonstrate clinical improvement in 93% of women with a median follow-up of 10.7 months. Long-term follow-up (34.2 months) showed that 82.4% of women reported sustained significant improvement of symptoms after UAE. The meta-analysis indicated that hysterectomy after UAE was needed in 13% of women with adenomyosis, mostly around 12 months after UAE. Most patients experienced some form of mild postembolization syndrome. The risk of permanent amenorrhea was approximately 21%, occurring 3 to 6 months after UAE. However, permanent amenorrhea occurred only in women older than 45 years of age at the time of UAE. No deaths or serious adverse events related to UAE for adenomyosis were reported.

TIPS AND TRICKS

• Adenomyosis should be remembered as a potential cause of disabling symptoms such as HMB, heavy menstrual pain with or without bulk-related symptoms, and fertility issues in premenopausal women.

• A junctional zone thickness over 12 mm as measured on T2 weighted images with contrast-enhanced T1 weighted MRI is considered diagnostic of adenomyosis.

• Differences in the timing of when UAE is performed during the menstrual cycle does not have a significant effect on efficacy for adenomyosis.

• The angiographic end point of embolization recommended in patients with adenomyosis is the elimination of the adenomatous tissue blush with complete stasis of flow of contrast at the distal end of the ascending segment of both uterine arteries. This likely provides better infarction rates and durable clinical results.

• Calibrated microspheres are the embolic agent of choice for adenomyosis because they can provide the deep penetration needed for optimal infarction of adenomatous tissue. The use of agents that result in a more proximal embolization may explain the higher failure rates reported in adenomyosis patients.

CONCLUSIONS

During the last decade, the UAE technique has undergone several refinements and extended its application beyond the embolization of uterine fibroids. Nowadays, women with pure adenomyosis or adenomyosis with fibroids are potential candidates for UAE. Many studies have reported the success of UAE with a long-lasting positive effect of adenomyosis-related symptoms with improvement or elimination of HMB, pelvic pain, and bulk-related symptoms. With the level of evidence available, UAE has proven to be an attractive treatment option and a valuable alternative to hysterectomy for women with symptomatic adenomyosis.

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