Uterine myomata: Organ-preserving surgery

Uterine myomata: Organ-preserving surgery

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Best Practice & Research Clinical Obstetrics and Gynaecology xxx (2015) 1e7

Contents lists available at ScienceDirect

Best Practice & Research Clinical Obstetrics and Gynaecology journal homepage: www.elsevier.com/locate/bpobgyn

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Uterine myomata: Organ-preserving surgery* Francois Closon, MD, Togas Tulandi, MD, MHCM, Professor and Academic Vice Chairman of Obstetrics and Gynecology, and Milton Leong Chair in Reproductive Medicine * Department of Obstetrics and Gynecology, McGill University, Montreal, Canada

Keywords: myoma laparoscopic myomectomy operative hysteroscopy robotic myomectomy radiofrequency ablation

Most women with uterine myoma are asymptomatic and do not require any treatment. However, myoma can also lead to menorrhagia, pressure symptoms, abdominal pain, and infertility. Management of symptomatic women with myoma depends on several factors, including age, desire for fertility, and myoma characteristics. Uterine myoma that distorts the uterine cavity, either submucous myoma or intramural myoma, with a submucous component reduces fertility, and is associated with increased uterine bleeding. The treatment of choice is hysteroscopic myomectomy or abdominal myomectomy, preferably by laparoscopy. Robotic assistance in laparoscopic myomectomy leads to outcomes similar to conventional laparoscopic myomectomy. However, it is expensive. Newer techniques include either laparoscopic or transcervical radiofrequency thermal ablation. © 2015 Elsevier Ltd. All rights reserved.

Introduction About 25% of women above 35 years of age have uterine myoma and most of them are asymptomatic. Symptoms are experienced by only a quarter of women with myoma. The main symptoms are menorrhagia, pressure symptoms, and abdominal pain. Infertility or repeated pregnancy loss could be experienced by women with submucous myoma or intramural myoma that distorts the uterine cavity.

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Theme of the journal: Avoiding Complications in Gynaecological minimal access surgery. * Corresponding author. McGill University, 687 Pine Ave West, F6.01, Montreal, QC H3A 1A1, Canada. Tel.: þ1 514 843 1650; Fax: þ1 514 843 1448. http://dx.doi.org/10.1016/j.bpobgyn.2015.09.005 1521-6934/© 2015 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Closon F, Tulandi T, Uterine myomata: Organ-preserving surgery, Best Practice & Research Clinical Obstetrics and Gynaecology (2015), http://dx.doi.org/10.1016/ j.bpobgyn.2015.09.005

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The relationship between myoma and the endometrium is the key point in the management of symptomatic women with myoma [1]. For example, myomectomy for submucous myoma or laparoscopic myomectomy for intramural myoma with submucous component will increase the subsequent live birth rate [2]. The recent classification of the Federation International of Gynecology and Obstetrics clearly identified the type of fibroids as they are defined in terms of their relationship with the endometrium and the uterine serosa [3]. Management of women with uterine myoma depends on several factors, including age, desire for fertility, symptoms, and size and location of the myoma. Several treatment methods are available for uterine myoma such as expectant management, medical treatment, uterine artery embolization, excision or ablation of the myoma, and hysterectomy. Nonsurgical treatment of uterine myoma and hysterectomy are beyond the scope of this study. Preoperative Careful history taking, physical examination, and pelvic imaging are important. In most cases, a thorough transvaginal ultrasound with or without abdominal scan is usually sufficient. In general, symptoms caused by fibroids are subjective. It is noteworthy that other conditions such as endometriosis or adenomyosis could coexist with myoma [4,5]. Management of the myoma without considering such coexistence might lead to treatment failure. Before the commencement of surgical approach, management of other alternative uterine myoma, including the risks and implications of each treatment, should be discussed. Prior to hysteroscopic myomectomy, long-acting gonadotropin-releasing hormone agonist (GnRHa) was regularly administered 4 weeks before the start of the procedure. It reduces the thickness of the Q 6 endometrium, making it visible. It is also associated with decreased fluid absorption [6]. GnRHa was used thrice monthly for 4 months before surgery for submucous myoma of 3 cm, which completely removes myoma in a single setting. In order to allow laparoscopic approach, the same regime is used for a larger uterus of >18 gestational weeks. Thrice-monthly administration of one dose of GnRHa results in a 30% shrinkage of the myoma volume [7]. Ulipristal acetate, a selective progesterone receptor modulator, can also be used. New studies to determine whether administration of ulipristal acetate for 3 months consistently reduces the size of the myoma are still needed. The use of GnRHa or ulipristal acetate can result in myoma degeneration, which makes the myoma soft. Manipulation and enucleation are more difficult for soft myoma than solid myoma. Submucous myoma Type 0, 1, and 2 myomas (submucous myoma) are associated with infertility, miscarriages, and menorrhagia. Hysteroscopic myomectomy is the best surgical treatment for type 0 and 1 myomas. Although in most cases, type 2 myoma can be removed by hysteroscopy, large type 2 myoma of >3 cm that occupies the entire myometrium is better removed by laparoscopy, thereby completely removing the myoma. In women with repeated pregnancy loss, myomectomy decreases the miscarriage rate and increases the live birth rate from 23% to 52% [8]. Hysteroscopic resection of type 2 myoma could be challenging and associated with a longer operating time. The type of myoma and the duration of surgery seem to be the most important factors influencing fluid deficit [9]. In order to improve resection of myoma, a hysteroscopic morcellator has been developed, which automatically and rapidly removes tissue fragments during the resection and improves visualization during the entire the procedure [10]. Intramural myoma The need and results of myomectomy in infertile women with intramural myoma and no distortion of the uterine cavity remain controversial. In general, removal of this type of myoma does not improve the outcome of pregnancy [2]. Please cite this article in press as: Closon F, Tulandi T, Uterine myomata: Organ-preserving surgery, Best Practice & Research Clinical Obstetrics and Gynaecology (2015), http://dx.doi.org/10.1016/ j.bpobgyn.2015.09.005

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Laparoscopic myomectomy is associated with less blood loss, less pain, shorter hospital stay, and faster recovery than laparotomic myomectomy [11,12]. However, it is technically demanding, and requires expertise in laparoscopic suturing. Saccardi et al. reported increased bleeding and operating time for the removal of intramural myoma >8 cm or subserosal myoma >12 cm [13]. Several methods have been proposed to reduce bleeding, including the thrice-monthly administration of one dose of GnRHa for 4 months before myomectomy. Intravaginal administration of one dose of misoprostol 400 mcg an hour before surgery is also beneficial [14]. It is a common practice to infiltrate dilute solution of vasopressin (20 units per 100 mL normal saline) into the myometrium before making the myomectomy incision. Because of the possible side effects such as cardiac arrhythmia and change in blood pressure, the anesthesiology team should be informed before injecting vasopressin [15,16]. Barbed suture facilitates laparoscopic suturing more effectively than conventional sutures [17,18]. Postmyomectomy adhesions Most myomectomies are associated with intra-abdominal adhesions, which can cause infertility, bowel obstruction, and abdominal pain [19]. In order to reduce adhesion formation, surgery should be performed using microsurgical principles including gentle tissue handling, meticulous hemostasis without excessive coagulation, and copious irrigation to prevent serosal drying [20]. Laparoscopy is associated with lesser adhesion than laparotomy. However, adhesion-reducing substances should also be used. Many pharmacological agents, such as anti-inflammatory drugs, both steroidal and nonsteroidal, GnRHa, and heparin, have been proposed to prevent the formation of adhesion, but the results have been unfavorable [21]. Peritoneal instillates capable of producing hydroflotation including isotonic solutions, such as normal saline or Ringer's lactate, have been tested; however, as the peritoneum has a high capacity of fluid absorption, the solution will not be retained long enough to prevent adhesion formation [22]. Compared with isotonic solution, 32% dextran (Hyskon, Pharmacia Inc., Uppsala, Sweden) stays longer in the abdominal cavity. However, randomized studies showed that it was ineffective. The only agent approved by the US Food and Drug Administration (FDA) to be used by laparoscopy is 4% icodextrin solution (Adept®, Baxter Healthcare, Deerfield, IL, USA), another peritoneal instillate that is associated with lesser adhesion formation than Ringer's lactate [23]. The widely used adhesion-preventing substances are adhesion barriers such as oxidized regenerated cellulose (Interceed: Gynecare, Somerville, NJ, USA) and combined hyaluronic acid (HA) and carboxymethylcellulose (Seprafilm: Genzyme Corporation, Cambridge, MA, USA). HA is one of the components of several gels and adhesions barriers. It is a linear polysaccharide that naturally protects tissue, and has been shown to reduce the formation of adhesions [24]. It is marketed in combination with carboxymethylcellulose (Sepraspray or Seprafilm, Genzyme Corporation, Cambridge, MA, USA) and as auto-cross-linked HA (Hyalobarrier gel: Nordic Pharma, Reading, UK). In a meta-analysis including 335 patients who underwent hysteroscopic procedure or laparoscopic myomectomy, the authors showed that auto-cross-linked HA significantly reduced intraperitoneal or intrauterine adhesions [25]. Pregnancy rate of women who underwent laparoscopic myomectomy was also higher in the treated than the control group (77% vs. 38%) [26]. However, the use of Seprafilm by laparoscopy is cumbersome as the fabric easily sticks together. Oxidized regenerated cellulose (Interceed, Gynecare, Somerville, NJ, USA) is the most popular adhesion barrier in gynecology. It consists of a knitted fabric, which can be easily applied on the tissue by laparoscopy. It becomes a gelatinous coat that prevents migration of fibroblasts, and is totally resorbed within few weeks. Before using Interceed®, hemostasis should be secured as bleeding is reduced [27,28]. Laparoscopically assisted myomectomy The procedure is similar to laparoscopic myomectomy except that a transverse suprapubic skin incision is made to allow delivery of the myoma and to repair the myomectomy incision. The length of the incision is up to 4 cm. Laparoscopically assisted myomectomy (LAM) offers advantages of both Please cite this article in press as: Closon F, Tulandi T, Uterine myomata: Organ-preserving surgery, Best Practice & Research Clinical Obstetrics and Gynaecology (2015), http://dx.doi.org/10.1016/ j.bpobgyn.2015.09.005

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laparoscopy and laparotomy. In a retrospective study of 116 patients who underwent laparoscopic myomectomy or LAM, the authors reported no significant difference in surgical complications, length of hospital stay, or recovery time. Estimated blood loss was higher in the LAM group (303 vs. 200 ml), but the mean operating time was lower (66 vs. 94 min) [29]. Several factors could contribute to these differences, including the surgeon's expertise and familiarity of laparoscopic suturing and the size and location of the myoma. Extraction of myoma from the abdominal cavity In LAM, myoma can be easily removed by abdominal incision. In laparoscopic myomectomy, the myoma is usually removed in pieces, using a morcellator. Following a case of a physician who underwent laparoscopic morcellation of uterine sarcoma, the safety of the procedure has been questioned and has led to an amplified chain reaction. This included a communication from the FDA on April 17, 2014, discouraging the use of laparoscopic morcellation for removal of uterus or uterine fibroids because “it poses a risk of spreading unsuspected cancerous tissue, notably uterine sarcomas, beyond the uterus.” As a consequence, Johnson and Johnson, one of the companies that produce an electric morcellator (Morcellex), subsequently withdrew their product from the market [30]. In a systematic review, Pritts et al. reported poor evidence for the association of morcellation with worse outcome than en bloc uterine removal [31]. Although the incidence of leiomyosarcoma is very rare (0.64 per 100,000 women), it poses severe threats [32]. In any event, gynecologists are trying to find a method that prevents the scattering of tissue fragments inside the abdominal cavity. LAM is one such method, but it needs an abdominal incision. Another method is removal of the specimen through a colpotomy incision. The elasticity of the vagina allows removal of even a large specimen. However, the specimen can also be morcellated through a colpotomy opening [33,34]. A relatively new technique is laparoscopic in-bag morcellation. The endoscopic bag is expanded by passing CO2 gas, and an ancillary laparoscopic trocar is placed directly through the bag allowing placement of the laparoscope. This technique appears to be safe, but the devices are used in an off-label setting and requires several adjustments [35]. Studies to develop safe morcellators are currently ongoing [36]. Radiofrequency thermal ablation A few authors prefer ablation of the myomas (myolysis) over myoma removal. Primarily, energy was obtained from Nd:YAG laser, followed by other kinds of sources such as monopolar and bipolar energy or cryotherapy [37]. However, laparoscopic myolysis is associated with adhesion formation, and uterine rupture has been reported as well. Recently, radiofrequency thermal ablation has been performed to remove myoma [38]. The procedure is carried out by placing a probe inside the myoma under laparoscopy and laparoscopic ultrasound imaging. Seven titanium prongs are then used, and the cell is activated by heating it to 100 C. The extent of the damage depends on the distribution of the prongs. It takes approximately 5 min to ablate a 3-cm myoma. A volume reduction of up to 85% at 12 months has been reported [38,39]. However, laparoscopic intra-abdominal ultrasound is not easy to perform, and the procedure needs a laparoscopic and an ultrasound monitor. Further, there is no tissue diagnosis. A similar device is used for transcervical uterine fibroid ablation, the VizAblate System® (Gynesonics, Redwood City, CA, USA). It combines real-time sonography and radiofrequency for ablation and consists of an intrauterine ultrasound probe inserted into the uterine cavity. An electrode is inserted into the myoma under ultrasound guidance [40], and a >50% reduction in the myoma volume has been reported [41]. Robotic-assisted laparoscopic myomectomy Robotic surgery has several advantages such as a three-dimensional vision system, intuitive and multidirectional movements with a wristed instrumentation, and a higher comfort of work as the Please cite this article in press as: Closon F, Tulandi T, Uterine myomata: Organ-preserving surgery, Best Practice & Research Clinical Obstetrics and Gynaecology (2015), http://dx.doi.org/10.1016/ j.bpobgyn.2015.09.005

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surgeon seats at the surgical console [42]. It facilitates laparoscopic suturing, yet there is no tactile feedback [43]. However, it is expensive, associated with an increased operating time, and requires at least four incisions [44]. In addition, it is associated with increased blood loss, complications, length of hospital stay, and operating time compared with conventional laparoscopic myomectomy. Thus, it appears that robotic-assisted laparoscopy myomectomy offers no additional short-term benefit compared to its conventional laparoscopic counterpart [45]. In any event, it is valuable for obese women [46]. Barbed suture for myomectomy Barbed suture, a relatively new type of suture, consists of a standard monofilament suture with tiny barbs cut into the length of the suture in a helical array set facing in opposite directions. Because of the presence of barbs on the suture, it approximates the tissue without the need of a surgical knot facilitating laparoscopic suturing. Another advantage of barbed suture is that it maintains tension of the suture line during suturing. The presence of barbs allows good approximation of the tissue at the beginning of suturing, leading to early hemostasis. In a meta-analysis, Tulandi and Einarsson found that the use of barbed suture for uterine closure is associated with reduced operating and suturing times and decreased blood loss [18]. Postoperative adhesion formation with barbed suture is similar to that of conventional suture [47]. However, the barbs tend to stick to the tissue, and small bowel obstruction related to barbed suture has Q 7 been reported [48,49]. Cutting the tail of the barbed suture flush to the tissue could be helpful. In practice, we regularly cover the suture line with an adhesion barrier.

Practice points  Myoma that distorts the uterine cavity is associated with infertility and repeated pregnancy loss  Myomectomy should be limited for women of childbearing age  Pelvic imaging is essential for mapping myoma and chooses the best surgery approach  As adhesion formation is closely related to myomectomy, microsurgical principles and adhesion-reducing substances should be used  Barbed suture for uterine closure is less technically demanding and facilitates laparoscopic suturing

Research agenda    

Radiofrequency thermal ablation for women with desire for childbearing or future fertility Preoperative effects of ulipristal acetate on myomectomy Safe myoma morcellation technique Randomize trial on robotic surgery for myomectomy

Conflict of interest Dr. Tulandi is an advisor for Acatvis Inc, and AbbVie Canada; Dr. Closon has no conflict of interest. Q8

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