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Abstract

Objective

To assess the long-term efficacy and quality of life associated with laparoscopic bilateral uterine artery occlusion plus partial resection of symptomatic adenomyosis.

 

Study design

A total of 182 eligible patients with symptomatic adenomyosis were treated by laparoscopic bilateral uterine artery occlusion plus partial resection of adenomyosis from July 2003 to July 2009. Menstrual blood loss was measured using a pictorial blood loss assessment chart. Pain intensity during menstruation was evaluated on a 10-point visual analog scale (VAS). Health-related quality of life was measured using the WHOQOL-BREF.

 

Results

A total of 179 patients with 3 years follow-up were enrolled in this retrospective study. No severe complications were noted during the surgical procedure or follow-up period. The mean postoperative dysmenorrhea and menorrhagia scores were significantly improved (all p < 0.01) at 3, 12 and 36 months postoperatively, compared with preoperative scores. The volume of the uterus was continuously reduced at 3, 6, 12 and 36 months postoperatively, and had shrunk by 58.3% at 36 months after surgery, compared with the preoperative volume. Notably, only 1.7% (3/179) of patients had received a hysterectomy at 36 months follow-up. In addition, patient's health-related quality of life scores were significantly increased (p < 0.01) compared with preoperative scores.

 

Conclusion

Laparoscopic bilateral uterine artery occlusion plus partial resection of symptomatic adenomyosis is effective. There was a very low recurrence rate detected by ultrasound at 36 months.

 

Keywords

Adenomyosis; Laparoscopy; Uterine artery occlusion; Partial resection
 

1. Introduction

Adenomyosis is a prevalent, benign gynecologic condition, in which endometrial tissue invades the myometrium, causing myometrial inflammation and hypertrophy, often resulting in menorrhagia and dysmenorrhea. The reported frequency of adenomyosis ranges from 35% to 50% [1]. Hysterectomy can provide a cure for adenomyosis in all cases, but involves removing the uterus. Progress in imaging and endoscopic techniques, however, has allowed the development of various minimally invasive procedures. Among these, uterine artery embolization (UAE) and laparoscopic uterine artery occlusion (LUAO) are being used to treat symptomatic fibroids [2] and [3].

 

The mechanisms responsible for the effects of UAE and LUAO are not yet fully understood. In 2000, Burbank suggested the unifying hypothesis of transient uterine ischemia, whereby occlusion of the uterine arteries causes the blood flow to stop, with consequent thrombus formation in small vessels. Different pathophysiological changes occur in small vessels in the normal myometrium and in myomas. After a few hours, clots are lysed in myometrium vessels, but not in vessels in myomas, resulting in recovery of the myometrium, but necrosis of the myoma [2] and [3].

 

UAE has recently been reported for the treatment of adenomyosis, though these studies have focused more on the clinical success of UAE in patients with adenomyosis, rather than on trying to explain the causes of treatment failure after UAE. Several more recent studies have provided additional insights into UAE in patients with adenomyosis. In 2005, Weichert et al. [4] evaluated hysterectomy specimens from two women with adenomyosis with failed UAE. They found that adenomyosis foci remained unaltered at 34 and 48 weeks post-embolization, and no morphological changes were seen in the endometrium. Particles were randomly distributed throughout the outer half of the myometrium. Similarly, Dundr et al. [5] examined three hysterectomy specimens from women with adenomyosis who underwent UAE. Again, particles were randomly distributed throughout the myometrium, with no morphological changes in areas of adenomyosis. They suggested that UAE had failed in these cases [5] and [6].

 

We hypothesized that the success rates of UAE and LUAO may be correlated with the extent and depth of muscle invasion. Bilateral LUAO plus partial resection of adenomyosis has therefore been carried out in our hospital since 2003. A previous study of the midterm results [7] revealed significant symptom resolution in 35 of the 37 patients with symptomatic adenomyosis. The volume of the uterus decreased by almost 60%. Thirty-six (97.3%) of the 37 women experienced marked improvement in chronic pelvic pain.

 

The aim of the current study was to determine the long-term clinical efficacy of and quality of life (QOL) following bilateral LUAO plus partial resection of adenomyosis.

 

2. Materials and methods

We analyzed data for all patients treated for symptomatic adenomyosis between July 2003 and July 2009 at the Gynecological Department of Yang-Pu District Central Hospital. This was a retrospective review of a prospectively collected database. The study was approved by the hospital ethics committee.

 

The criteria for adenomyosis were: myometrial cyst, distorted and heterogeneous myometrial echotexture, and a globular and/or asymmetric uterus. A total of 193 patients with symptomatic adenomyosis were invited to participate if they met the following inclusion criteria: (1) preoperative examination and postoperative pathological examination excluded malignant disease and fibroids (uterine adenomyoma diagnosed by preoperative ultrasound, uterine fibroids by postoperative pathology); (2) history of failed drug treatment including progestin, gonadotropin-releasing hormone agonist, and mifepristone, and the last injection of gonadotropin-releasing hormone agonist was at least 6 months before the operation; (3) no desire for a future pregnancy; and (4) size of the adenomyosis lesion >2 cm, estimated by preoperative ultrasound.

 

Eligible patients (n = 182) ( Fig. 1) were thoroughly counseled, and informed consent was obtained from all patients. The possibilities of treatment failure, recurrence of symptoms, and hysterectomy were explained.

 

        
        

 

Menstrual blood loss was measured using a pictorial blood loss assessment chart. Pain intensity during menstruation was evaluated using a 10-point visual analog scale (VAS) [8]. A reduction of 50% compared with the score before surgery was considered to indicate efficacy. The definition of menorrhagia was abnormally heavy and prolonged menstrual bleeding at regular intervals. Transvaginal sonography was performed by the same physician before and after surgery. The volume of the uterus was calculated using the prolate ellipse equation (length × width × height × 0.523).

 

Health-related QOL was measured preoperatively and at 12 and 36 months after surgery, using the World Health Organisation (WHO) QOL-BREF. The WHOQOL-BREF consists of 28 items and covers four aspects of QOL, including physical domain (D1), psychological domain (D2), social relationship domain (D3), and environmental domain (D4), encompassing a total of 26 features. There are also two general questions, one on the overall QOL (Q1) and the other on overall health condition (Q2). In accordance with the provisions of the WHO, the score for each area was four times the average of all entry points. The higher the score, the better the patient's QOL.

 

2.1. Surgical techniques

All laparoscopic operations were performed under routine general anesthesia. Bilateral LUAO combined with partial resection of adenomyosis was performed as described previously [7] and [9]. The triangular area enclosed by the round ligament, external iliac vessels, and infundibulopelvic ligament was chosen as the incision site. The ureter and internal iliac artery were exposed. The uterine artery was isolated and occluded with bipolar forceps (Gyrus ACMI Inc., UK) or PK forceps (Gyrus ACMI Inc.) under direct vision. Bipolar forceps or PK forceps were used for thermal coagulation of tissues or blood vessels for hemostasis. Adenomyosis can be sub-classified as focal (Fig. 2) or diffuse. The former can usually be almost completely resected. The raised portion of the focal adenomyosis was dissected using a monopolar incision. Adenomyosis tissue was then excised from the edges of the defect to access the healthy myometrium via a monopolar incision, or with scissors until soft tissue was reached. In the latter case, forceps or a suction tube were used to explore the demarcation line between the normal myometrium and adenomyosis, and the diseased part was then removed as completely as possible. All the removed tissues were morcellated using a tissue morcellator. In cases where the uterine cavity was entered, figure-of-eight sutures were used for closure, leaving as little dead space as possible. The muscle and serosa were repaired with continuous inverting zero polyglycolic acid sutures (Safil, B. Braun, Rubi, Spain) (Fig. 3).

 

         

 

         

 

The material for frozen sections was taken during the operation.

 

2.2. Clinical follow-up

All patients were followed up at 3, 12, and 36 months after surgery. Follow-up visits included assessments of changes in dysmenorrhea, menorrhagia and health-related QOL. Health-related QOL was followed up at 12 and 36 months after surgery. The volume of the uterus was also measured at follow-up using ultrasound (abdominal and vaginal).

 

2.3. Statistical analysis

The per-protocol analysis was based on data from patients included in the per-protocol cohort. Data are shown as mean ± standard deviation. Comparisons of pre- and post-operative scores were based on paired-sample t-tests. Differences were considered statistically significant at p < 0.05 (SPSS 16.0.0, SPSS, Inc., Chicago, IL, USA).

 

3. Results

A total of 193 patients were enrolled between July 2003 and July 2009 at the Gynecological Department of Yang-Pu District Central Hospital. Of these, 11 patients were excluded postoperatively, including six patients who transferred to classic intrafascial supracervical hysterectomy on the day of surgery because they were concerned about treatment failure and recurrence, and five patients who were excluded through pathological examination because of fibroids (four patients) or malignant disease (one patient with sarcoma). A further three patients were lost to follow-up. Thus 179 patients with a follow-up period of 3 years were enrolled in the study. The characteristics and diagnoses of the enrolled patients are summarized in Table 1. A total of 78 patients reported dysmenorrhea and 66 patients experienced menorrhagia. Thirty-five patients experienced dysmenorrhea and menorrhagia. Anemia was reported by 115 patients.

 

        
        

 

The operative and postoperative data are shown in Table 2. All patients completed the surgery and none was converted to laparotomy because of laparoscopic surgical failure.

 

        

 

Pathological examination of samples from 107 participants showed adenomyoma, 72 were reported as adenomyosis, 47 had accompanying fibroids, and 28 had accompanying endometrial cysts.

 

No severe complications were noted during the surgical procedure or follow-up. One patient had abdominal drainage of 1400 ml of light-pink fluid during the first 24 h after operation. This was considered to be retention of irrigation fluid contaminated with blood and the patient recovered uneventfully without treatment. Four patients had mild paralytic ileus, but recovered with appropriate measures. Three patients underwent hysterectomy because of persistent dysmenorrhea at 22, 25, and 31 months after surgery, respectively (Fig. 4). Nine patients had amenorrhea at 12 months after surgery (the ages ranged from 47 to 52 years (49.29 ± 3.98 years)), and 12 were menopausal at 36 months after surgery (the ages ranged from 45 to 52 years (50.24 ± 4.83 years)). Eight patients required analgesic treatment because of tolerable dysmenorrhea at 36 months follow-up. Six patients had persistent abnormal menstruation (preoperative MRI was performed to exclude organic disease); four of these underwent transcervical resection of polyps and two underwent transcervical resection of the endometrium because of dysfunctional uterine bleeding.

 

        

 

Overall, 176 (98.3%) of 179 women experienced marked improvements in dysmenorrhea, menorrhagia and uterine volume at 3, 12, and 36 months after surgery. The mean postoperative dysmenorrhea scores were 3.5 ± 1.5, 4.4 ± 1.6, and 4.2 ± 1.5 at 3, 12 and 36 months respectively, compared with 7.7 ± 1.8 before treatment, indicating significant improvement (all p < 0.01). The uterus thus shrunk by 31.5%, 56.5%, and 58.3% at 3, 12, and 36 months, respectively, compared with the volume before treatment, indicating a significant improvement (all p < 0.01). The differences in dysmenorrhea, menorrhagia, and volume of the uterus at 3, 12, and 36 months are shown in Table 3.

 

        

 

Overall patient scores were significantly higher (p < 0.01) at 12 and 36 months’ follow-up compared with the preoperative scores, because of improvements in physical, psychological, social relationship and environmental domain scores (all p < 0.01) ( Table 4).

 

        

 

4. Comments

UAE or LUAO can be used for the treatment of uterine myoma and adenomyosis, though the therapeutic mechanism of uterine artery occlusion remains unclear. Burbank's suggestion [2] and [3] that blood coagulation and fibrinolysis may differ between myomas and the myometrium after UAE has been supported by magnetic resonance imaging and computed tomography, and by investigations of the plasminogen activator/plasminogen activator inhibitor (PAI) system [10], [11] and [12]. Cheng et al. found reduced expression of urokinase (uPA) protein and increased expression of PAI-1 in myomas compared with the myometrium. They suggested that low uPA and high PAI-1 expression in myomal tissue might reflect an inability to initiate the fibrinolytic processes, making thrombolysis difficult or even impossible in myoma vessels, and leading to tumor infarction [10].

 

UAE or LUAO alone for the treatment of adenomyosis is controversial, although some authors consider them to be clinically effective [6] and [12]. However, in a study of UAE for the treatment of uterine adenomyosis with or without uterine leiomyomata, 27.5% of patients (11/40) required subsequent hysterectomy or dilatation and curettage for therapy failure, and the authors therefore concluded that UAE was ineffective for the treatment of adenomyosis [13]. Some authors have also reported poor results, and have suggested that laparoscopic uterine artery ligation alone may not be effective for the treatment of symptomatic adenomyosis [14].

 

We hypothesized that the success rates of UAE and LUAO may be related to the extent and depth of muscle invasion, and that these techniques may be more effective in small or residual adenomyosis. Some studies have also suggested that the effect of UAE may depend on primary fibroid size, location, or the total number of fibroids [15] and [16]. Bilateral LUAO plus partial resection for symptomatic adenomyosis has therefore been carried out in our hospital since 2003, with good clinical outcomes [7]. Partial resection of adenomyosis can reduce the lesion volume, which is responsible for dysmenorrhea and menorrhagia. LUAO can cause necrosis of the residual lesion about 6 h after uterine artery block, while collateral vessels from the ovarian artery, the vaginal artery and pelvic small vessels can be used for reconstruction, the normal uterus remains alive and its physiological activity is restored [9] and [10]. In the current study with 3 years of follow-up, the volume of the uterus shrank by 56.5% at 12 months after surgery compared with the preoperative volume, and the shrinkage rate was 58.3% at 36 months after surgery. Overall, 176 (98.3%) of 179 women experienced marked improvements in dysmenorrhea and menorrhagia. Eight patients required analgesic treatment because of tolerable dysmenorrhea at 36 months follow-up. Notably, only three patients required a hysterectomy because of failed treatment for symptomatic adenomyosis at 36 months follow-up.

 

Patients with adenomyosis are increasingly concerned with maintaining the physiologic function of the uterus, and express a wish to preserve organ integrity. Indeed, some experts believe that the uterus may affect a woman's intellectual health. A study of the negative impacts of postoperative fatigue on the daily lives of patients recovering from hysterectomy showed that 74% of patients felt fatigued after hysterectomy, which persisted for about 11 weeks, while 45% of patients had postoperative signs of emotional instability [17]. Interestingly, our study found significantly increased postoperative health-related QOL scores associated with improvements in physical, psychological, social relationship and environmental domain scores.

 

No patients in the current study required conversion to laparotomy because of laparoscopic surgical failure. Based on our previous experience, surgery can be difficult in patients with large and severe diffuse adenomyosis, but there were no such patients in the present study.

 

Nine patients had amenorrhea at 12 months after surgery: the ages ranged from 47 to 52 years (49.29 ± 3.98 years). We hypothesized that the ovary blood flow of some patients may be mainly from the uterine artery.

 

This study had some limitations. First, use of a symptom score of 10 as a preoperative baseline might have led to bias. Although it would have been ideal to compare absolute symptom scores before surgery with those after surgery, it is difficult for patients to define absolute symptom values, especially for menorrhagia, before surgery. We therefore compared relative symptom scores, which were more intuitive. Second, a controlled study with more cases is needed to allow decisive conclusions to be drawn.

 

Bilateral LUAO plus partial resection of adenomyosis of symptomatic adenomyosis is an effective treatment, resulting in improved postoperative QOL, but the possibilities of treatment failure, recurrence, and the need for hysterectomy should be carefully explained to all patients.

 

Acknowledgement

We would like to thank our colleagues for help with data collection.