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A randomized, controlled study comparing minilaparotomy versus isobaric gasless laparoscopic assisted minilaparotomy myomectomy for removal of large uterine myomas: Short-term outcomes
European Journal of Obstetrics & Gynecology and Reproductive Biology 145 (2009) 104–108
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European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
A randomized, controlled study comparing minilaparotomy versus isobaric gasless laparoscopic assisted minilaparotomy myomectomy for removal of large uterine myomas: Short-term outcomes Jie Tan a, Yangyan Sun a, Baoliang Zhong b, Huihua Dai c, Daoyuan Wang a,d,* a
Department of Gynaecology, Jiangyin Hospital, Medical School of Southeast of China University, No. 35 East of Renming Road, Jiangyin City, Jiangsu Province 214400, PR China School of Public Health, Peking University, No. 38 Xueyuan Road, Beijing 100083, PR China Department of Gynaecology, Jiangsu People Hospital, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing City, Jiangsu Province 210029, PR China d AmMed Cancer Center, Shanghai Ruijin Hospital, Medical School of Shanghai Jiaotong University, Shanghai 200025, PR China b c
A R T I C L E I N F O
A B S T R A C T
Article history: Received 9 April 2008 Received in revised form 2 March 2009 Accepted 12 April 2009
Objective: To compare the operative data and early postoperative outcomes for myomectomy performed by minilaparotomy (MLT) with isobaric laparoscopic assisted minilaparotomy myomectomy (LM) in a series of patients with large uterine myomas (5 cm) randomly assigned to each surgical technique. Study design: 80 patients were randomized blindly using a computer randomization list to MLT (n = 40) or LM (n = 40). Results: The mean (SD) operating time was significantly shorter after LM than after MLT (75.50 25.70 vs 96.00 26.20 min; p < 0.01). Intraoperative blood loss was less with LM (72.15 44.00 vs 96.21 38.50 ml; p < 0.05), and DHb was less with LM (1.21 0.55 vs 1.64 0.57; p < 0.05). No intraoperative complications occurred, and no case was returned to the theater in either group. No conversion to standard laparotomy was necessary. Hospitalization was shorter after LM than after MLT (4.30 1.20 vs 6.90 2.70 days; p < 0.01). Postoperative ileus was shorter after LM than after MLT (26.20 4.20 vs 40.50 4.90 h; p < 0.01). The mean VAS score at 12 h for abdominal pain was 5.5 0.7 in the LM group and 5.2 0.8 in MLT group (p < 0.05), whereas it was analogous in the two groups at 24 h, and at 48 h was 3.4 1.1 in the LM group and 4.2 1.1 in the MLT group (p < 0.05), and no difference between two groups was detected in the overall mean (at 12, 24 and 48 h). Conclusions: Several surgical and immediate postoperative outcomes were significantly better in the LM group than in the MLT group. Crown Copyright ß 2009 Published by Elsevier Ireland Ltd. All rights reserved.
Keywords: Uterine myomas Isobaric gasless laparoscopy Minilaparotomy Laparoscopic assisted minilaparotomy Myomectomy
1. Introduction Myomectomy is advisable for women who wish to preserve their childbearing capabilities, and it is needed when myomas are either asymptomatic, but growing rapidly and causing infertility/recurrent abortion, or symptomatic, causing abnormal uterine bleeding or pain [1–3]. Laparoscopy has developed into an effective tool that facilitates a wide range of pelvic surgery, including conservative myomectomy. The most common motive for conservative myomectomy, and hence laparoscopic myomectomy, is the patient’s will to avoid hysterectomy for personal reasons, or conserve fertility. Among the minimally invasive approaches to myomectomy, isobaric gasless laparoscopy (LA), using an abdominal wall-lifting
* Corresponding author at: Department of Gynaecology, Jiangyin Hospital, Medical School of Southeast of China University, No. 35 East of Renming Road, Jiangyin City, Jiangsu Province 214400, PR China. Tel.: +86 21 6270 4900; fax: +86 21 6270 4942. E-mail address: [email protected] (D. Wang).
device [4,5], minilaparotomy (MLT) [6–8] and laparoscopically assisted minilaparotomy (LM) [9] have been introduced recently. It is reported that myomectomy by isobaric gasless laparoscopy is feasible and safe, and it appears to offer several advantages over conventional laparoscopy with pneumoperitoneum [10,11]. Myomectomy via minilaparotomy has proved to be a safe and effective minimally invasive approach to myomectomy. Early discharge and return to normal activities were comparable with those for conventional laparoscopy, and the approach is far more cost effective [8]. There are two prospective trials in the literature comparing myomectomy with MLT and conventional LA using CO2 [12,13]: one compares MLT with isobaric gasless LA myomectomy and the other compares laparotomy (LT), MLT with LM. There are several studies of laparoscopic myomectomy for large myomas [4,11,14] or comparing it with abdominal myomectomy [15]. However, no study compares MLT with LM myomectomy for removal of large uterine leisomyomas. We undertook a randomized study comparing the operative data and early postoperative outcome for myomectomy performed
0301-2115/$ – see front matter . Crown Copyright ß 2009 Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2009.04.015
J. Tan et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 145 (2009) 104–108
by MLT compared with those by LM in a series of patients with large uterine leiomyomas (5 cm) randomly assigned to each surgical technique. 2. Materials and methods 2.1. Equipment and apparatus A video electronic laparoscope (Japan Olympus Co., Tokyo, Japan) and gasless lifting device and surgical apparatus (Japan Daoke Co., Tokyo, Japan) were used. 2.2. Patient selection The trial was performed in the Department of Gynaecology, Jiangyin Hospital, affiliated to Southeast of China University, Jiangsu Province, China. The study was previously approved by the local ethics committee. There was no financial interest or any arrangement with the companies producing the instruments used in the study or with competitor companies. There also was no direct payment to the authors from any source for the purpose of financing the writing of the manuscript, nor were there any other financial connections, direct or indirect, or other situations that might raise the question of bias in the work. From January 2005 to July 2007, all women with symptomatic uterine myomas requiring myomectomy were considered eligible for the study. The criteria for inclusion in the study specified the presence of one to three symptomatic intramural or subserosal myomas (without pedicle) associated with either infertility or fast growth and having a diameter of 5–10 cm.
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Major medical conditions, psychiatric disorders, current or past history of acute or chronic physical illness, premenstrual syndrome [16,17], current or past (a washout period of at least 6 months was considered appropriate before enrolment) use of hormonal drugs or drugs influencing cognition, vigilance, or mood, inability to complete the daily diary, and a history of alcohol abuse were all considered exclusion criteria. In addition, the following specific exclusion criteria were included: no desire to conceive, hypoechoic or calcified leiomyomas diagnosed at ultrasound [18], presence of submucosal leiomyomas or alterations of the uterine cavity screened by hysteroscopy and of other uterine or adnexal abnormalities at ultrasound (e.g., adenomyosis, abnormal endometrial thickness), pattern of hyperplasia with cytological atypia in the endometrial biopsy performed for abnormal uterine bleeding under hysteroscopy on suspected areas, an abnormal Papanicolau smear, and a positive urine pregnancy test. Lastly, symptomatic women who had not had a previous conception resulting in a live baby or with tubal/male factor subfertility were also excluded. Of the 109 women requiring myomectomy, 91 fulfilled the inclusion criteria and were recruited for the trial. 11 refused to participate. Written informed consent was obtained from each patient before randomization. The enrolment was closed when 80 patients were included, and 40 patients were allocated to each group (Fig. 1). 2.3. Study design At study entry, age, parity, and body mass index (BMI), leiomyoma-related symptoms, previous laparotomies, and asso-
Fig. 1. Flow diagram.
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J. Tan et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 145 (2009) 104–108
ciated medical conditions were assessed in each patient by the same clinician. All ultrasound examinations were performed transvaginally by an experienced operator, who assessed the presence/absence of associated pelvic diseases and evaluated uterine diameters, and myoma number, diameter and location. At study entry, a sample of venous blood was obtained from each patient between 8 and 9 am, after an overnight fast and bed rest during the early proliferative phase (second to third day of the cycle) to evaluate a complete blood count. Each woman gave her informed consent to be included into the study, which was previously approved by the local ethics committee. After enrolment by a physician, each woman had concealed randomization by a nurse to MLT (n = 40) or LM (n = 40), in a closed and dark-colored envelope until surgeries were assigned (before entering the operating room), using a computer-generated list of randomization. Thus, patients were assigned to one of the two surgical procedure groups (i.e., MLT or LM). All procedures were performed by the same surgeon (Dr. Ji Tan, M.D., who is equally experienced in both procedures) using the same technique. During each surgical procedure, total operative time, specifically the total duration of the surgical procedure, was calculated during the MLT or LM procedure beginning from abdominal skin incision, before Verres needle insertion, to skin suture.Intraoperative blood loss and intraoperative and postoperative complications were also evaluated and recorded in both groups. The intraoperative blood loss was differentially expressed as the difference between aspirated and irrigated liquid, and as the hemoglobin level decrease (DHb). Intraoperative complications were defined as laparotomic conversions and as bowel, bladder, ureteral, or vascular injuries. Laparotomic conversions were defined as open abdominal access through a more than 7-cm long skin incision. After intervention all patients received an intravenous bolus of tramadol (100 mg), followed by patient-controlled analgesia (tramadol 200 mg [2 vials] in 500 ml of saline solution) [19]. The postoperative analgesia was administered during the first 12 h after surgery. At the end of the surgical procedure the postoperative pain was also evaluated using VAS. The VAS consisted of a non-graduated 10 cm line ranging from ‘no pain’ to ‘pain as bad as it could be’ [20]. Postoperative pain was specifically assessed in each group at 0 h, 12 h, 24 h and 48 h after the surgical procedure. A blood sample was obtained and DHb was calculated for each woman 24 h after surgery. Durations of postoperative ileus and hospitalization were evaluated in both groups. Hospitalization time was defined from entry (the day of surgery) to discharge. 2.4. Surgical procedures All procedures were performed by the same surgeon (Jie Tan, MD, who was equally experienced in both procedures) using the same technique. The operator was informed of the type of intervention to be performed (whether MLT or LM) just before entering the operating room. Those assessing the outcome measures were blinded to the group assignment. A drug for thrombosis prophylaxis was not administered to any patient. After anesthesia administration, each patient was placed in a modified lithotomic position. Immediately before surgery, each patient received 2 g of IV cephalosporin as antibiotic prophylaxis, and if necessary, the same dose was repeated if the intervention lasted more than 2 h. In the LM group, a 10-mm port was inserted through the umbilicus to introduce the laparoscope, which was connected to a camera for video monitoring. An accessory 5-mm trocar was inserted into the abdomen to the left of the umbilicus. The video camera was used to identify the myoma and to obtain visual guidance for the insertion of the corkscrew through the peritoneum. The accessory trocar was used to insert operative instruments and the suction irrigation cannula. At the same time,
the minilaparotomic incision was performed. Minilaparotomy was performed with a 4- to 7-cm suprapubic incision. In the MLT group, procedures were performed without laparoscopic assistance. To avoid accidental extension of the minilaparotomies two double sutures were made at the ends of the skin incisions. The length and the distance from pubic symphysis of the skin incision varied according to leiomyoma diameter and localization. In both groups (MLT and LM), the uterine incision was performed using the same electrosurgical device with a cutting current of 70W. At the end of each intervention, the pelvis was washed with saline solution. No adhesion barrier or saline dextran macromolecular solutions were left in the peritoneal cavity. All operative samples were submitted for pathologic examination. 2.5. Statistical analysis At the study design, we considered the primary and secondary outcomes of the trial as intraoperative blood loss and postoperative abdominal pain VAS scores, respectively. For sample size calculation, we referred to the data of our clinical practice of seven cases for each procedure. A power calculation verified that 40 patients in each group would be necessary to detect a difference with an alpha error level of 5% and a beta error of 80%. Statistical analysis was performed using the Statistical Program/SPSS for Windows, version 11.5 (Chicago, IL, USA). Continuous outcome variables were analyzed using Student’s t-test. Discrete variables were analyzed with the chi-square test or Fisher’s exact test. The modification in the time observed in the both groups were compared by Analysis of Variance (ANOVA) for repeated measures. A p-value less than 0.05 was considered statistically significant. 3. Results Figure 1 illustrates the flow diagram of the present clinical study. The two groups of 40 patients each were obtained from randomization of 80 patients. No difference was observed between the two groups in uterine size, diameter of leiomyomas, main diameter of the largest leiomyoma, and number of leiomyomas, and the localization of leiomyomas was also similarly distributed in the two groups (Table 1). In all cases the estimated size and the histologic leiomyoma diagnosis, suspected before surgery through ultrasound, were confirmed, respectively, by macroscopic and microscopic examination of the enucleated tumors. Procedures were successfully performed for all the patients in both groups. The mean operating time was significantly shorter after LM than after MLT (76.4 20.7 vs 89.7 25.5 min; p = 0.012). Intraoperative blood loss was less with LM (79.9 12.9 vs 96.0 27.3 ml; p = 0.001), and DHb was less with LM (1.3 0.6 vs 1.6 0.6; p = 0.007) (Table 2). No intraoperative complications occurred, and no case was returned to the theater in either group. No conversion to standard laparotomy was necessary. With regard to the early postoperative outcome, no difference between two groups was detected in hospitalization days (1.8 0.5 vs 2.0 0.6 days; p = 0.194) and postoperative ileus (23.1 4.6 vs 22.9 4.2 h; p = 0.826) (Table 3). The repeated measures analysis of variance on postoperative abdominal pain VAS scores found that there was no difference of the VAS score among the four time points (0, 12 h, 24 h and 48 h), with the two groups combined (F = 852.726, p < 0.001); and no difference was found in the VAS score between the treatment groups, with values at all time points averaged and over time (p > 0.05) (Table 4). 4. Discussion The standard treatment of uterine fibroids – surgical excision and hysterectomy – has been promulgated as the one-size-fits-all
J. Tan et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 145 (2009) 104–108 Table 1 Main characteristics of the two study groups.
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Table 3 Early postoperative outcomes in the MLT and LA–MLT groups.
Group
MLT (n = 40)
LA–MLT (n = 40)
p-Value
Group
MLT (n = 40)
LA–MLT (n = 40)
p-Value
Age (years)a BMI (kg/m2)b Indication for myomectomy (n, %) Menstrual disorders Pelvic pain Unexplained infertility Rapidly grown myoma Previous major abdominal surgery (n, %) None One operation More than one operation Dominant myoma diameter (cm)a Proportion of patients according to number of myomas (n, %) <3 3 Dominant myoma (location): (n, %) Intramural Subserosal Dominant myoma (site): (n, %) Posterior Anterior Fundal
36.3 2.5 22.8 2.0
35.8 3.4 23.0 2.0
0.432 0.611 0.939
Postoperative ileus (h)a Hospitalization (days)a Conversion to laparotomy: n
23.1 4.6 1.8 0.5 0
22.9 4.2 2.0 0.6 0
0.826 0.194 NS
15 5 18 2
14 6 19 1
(37.5) (12.5) (45.0) (5.0)
a
(35.0) (15.0) (47.5) (2.5) 0.500
31 (77.5) 6 (15.0) 3 (7.5) 8.2 1.5
32 (80.0) 4 (10.0) 4 (10.0) 7.7 1.4
0.116 0.617
28 (70.0) 12 (30.0)
30 (75.0) 10 (25.0) 0.816
14 (35.0) 26 (65.0)
15 (37.5) 25 (62.5) 0.896
16 (40.0) 17 (42.5) 7 (17.5)
15 (37.5) 19 (47.5) 6 (15.0)
Some differences between groups were compared with Fisher’s exact Test method. Some cells with expected count less than 5 were merged in neighboring cells. a Values are expressed as mean standard deviation. There were no significant differences between the groups. b BMI, body mass index.
solution [21]. However, myomectomy is advisable for women who wish to preserve their childbearing capabilities, and it is needed when myomas are either asymptomatic, but growing rapidly and causing infertility/recurrent abortion, or symptomatic, causing abnormal uterine bleeding or pain [2,3]. The use of minilaparotomy in surgery for benign gynecologic disease has been well established [6]. Laparoscopic assisted myomectomy was first reported in 1994 [22]. In their review of 57 cases, the authors concluded that the procedure is far easier to teach than laparoscopic myomectomy because of the high degree of technical skill required for the latter. Similarly, myomectomy via minilaparotomy was shown to be a safe and effective minimally invasive approach with little bleeding, few complications, and early discharge and return to normal activities [6,7,8,23]. In a multicenter randomized, controlled study, Palomba et al. confirmed that minilaparotomic myomectomy is related to a lower global degree of surgical difficulty, and that it is a highly feasible and safe procedure, even if the laparoscopic approach remains, in expert hands, the procedure better related to the best short-term outcomes [24]. In two retrospective non-randomized studies, LM induced a similar blood loss, but fewer days of hospitalization, fewer days to
Table 2 Main operative parameters in the MLT and LA–MLT groups. Group
MLT (n = 40)
LA–MLT (n = 40)
p-Value
Total operative time (min)a Intraoperative blood loss (ml)a DHba
89.7 25.5 96.0 27.3 1.6 0.6
76.4 20.7 79.9 12.9 1.3 0.6
0.012 0.001 0.007
a
Values are expressed as mean standard deviation. Hb, haemoglobin.
Values are expressed as mean standard deviation. NS, not significant.
resume normal activity [21,25] and less postoperative use of analgesics [25]. The first randomized study reported that MLT and LM offer advantages in comparison with classic laparotomy [9]. To our knowledge, there are two prospective trials in the literature comparing myomectomy with MLT and conventional LM using CO2 [12,13]: one study compares MLT with isobaric gasless LA myomectomy and the other compares laparotomy (LA), MLT with LM. However, no study compares MLT with LM for removal of large uterine leisomyomas, although there are several studies of laparoscopic myomectomy for large myomas [4,11,14], or comparing it with abdominal myomectomy [15]. We undertook this randomized study comparing the operative data and early postoperative outcomes for myomectomy performed by LM compared with those by MLT in a series of patients with large uterine leiomyomas (5 cm) randomly assigned to each surgical technique. In our study, the operation was completed for all the patients using a minimally invasive approach (MLT or LM), and no conversion to standard laparotomy was necessary. No case in either group was returned to the operative theater. There was only difference of the VAS score among the four time points (0 h, 12 h, 24 h and 48 h) with the MLT and LM groups combined; and no difference the VAS score between the treatment groups, with values at all time points averaged and over time. Myomectomy for removal of large uterine myomas by LM is more feasible than by MLT [8]. It allows an accurate uterine repair. In particular, LM furnishes a more accurate cleaning of the pelvic cavity because after peritoneal closure, homeostasis is further controlled under videolaparoscopy, and repeated washings are performed for complete debris removal. LM allows clear vision of the pelvic cavity and furnishes visual guidance to the transperitoneal insertion of the corkscrew manipulator into the myoma, so that the operating time is clearly shorter with LM and intraoperative blood loss and DHb were less with LM. In this study a 4- to 7-cm transverse incision was performed for minilaparotomic access whereas there is not a standard universally accepted definition of ‘minilaparotomy’ used to compare correctly the results of the different studies. Pelosi et al. consider a laparotomy to be ‘mini’ with an incision of 2.5–5 cm [23], whereas
Table 4 The results of repeated measures analysis of variance on postoperative abdominal pain VAS scores. Group
At At At At a
0 ha 12 ha 24 ha 48 ha
MLT (n = 40)
LA–MLT (n = 40)
Treatment effect
8.4 1.2 5.0 0.7 4.3 1.1 4.1 0.7
8.0 1.0 5.3 0.6 4.2 0.9 3.4 0.6
0.079
p-Value* Effect of time
Interaction between treatment and time
<0.001
0.139
Values are expressed as mean standard deviation. The treatment effect denotes the difference between the treatment groups, with values at all time points averaged; the effect of time denotes differences among the three time points, with the two groups combined; and the interaction between treatment and time denotes the difference between the two groups over time. *
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J. Tan et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 145 (2009) 104–108
others give longer incision sizes, from 3 to 6 cm [8] up to less than 10 cm [6,10]. In conclusion, our results demonstrate that isobaric gasless LM and MLT can be a suitable option in uterine myomectomy. Several surgical and immediate postoperative outcomes were significantly better in the gasless LM group than in the MLT group. However, multi-center prospective randomized studies are required to confirm the results of this study, and to compare early and late clinical outcome of myomectomy by MLT with that performed by LM, including but not limited to: recurrence rate, fertility and obstetric outcome. References [1] Stewart EA. Uterine fibroids. Lancet 2001;357:293–8. [2] Vollenhoven BJ, Lawrence AS, Healy DL. Uterine fibroids: a clinical review. Br J Obstet Gynecol 1990;97:285–98. [3] Donnez J, Mathieu PE, Bassil S, Smets M, Nisolle M, Berliere M. Fibroids: management and treatment: the state of the art. Hum Reprod 1996;11:1837– 40. [4] Chang FH, Soong YK, Cheng PJ, et al. Laparoscopic myomectomy of large symptomatic leiomyoma using airlift gasless laparoscopy: a preliminary report. Hum Reprod 1996;11:1427–32. [5] Damiani A, Melgrati L, Marziali M, Sesti F. Gasless laparoscopic myomectomy: indications, surgical technique, and advantages of a new procedure for removing uterine leiomyomas. J Reprod Med 2003;48:792–8. [6] Benedetti-Panici P, Maneschi F, Cutillo G, Scambia G, Congiu M, Mancuso S. Surgery by minilaparotomy in benign gynecologic disease. Obstet Gynecol 1996;87:456–9. [7] Fanfani F, Fagotti A, Longo R, Marana E, Mancuso S, Scambia G. Minilaparotomy in the management of benign gynecologic disease. Eur J Obstet Gynecol Reprod Biol 2005;119:232–6. [8] Glasser MH. Minilaparotomy myomectomy: a minimally invasive alternative for the large fibroid uterus. J Minim Invasive Gynecol 2005;12:275–83. [9] Cagnacci F, Pirillo D, Malmusi S, Arangino S, Alessandrini C, Volpe A. Early outcome of myomectomy by laparotomy, minilaparotomy and laparoscopically assisted minilaparotomy. A randomized prospective study. Hum Reprod 2003;18:2590–4.
[10] Fanfani F, Fagotti A, Longo R, Marana E, Mancuso S, Scambia G. A prospective study of laparoscopy versus minilaparotomy in the treatment of uterine myomas. J Minim Invasive Gynecol 2005;12:470–4. [11] Alessandri F, Lijoi D, Mistrangelo E, Ferrero S, Ragni N. Randomized study of laparoscopic versus minilaparotomic myomectomy for uterine myomas. J Minim Invasive Gynecol 2006;13:92–7. [12] Damiani A, Melgrati L, Marziali M, Sesti F, Piccione E. Laparoscopic myomectomy for very large myomas using an isobaric (gasless) technique. JSLS 2005; 9:434–8. [13] Damiani A, Melgrati L, Franzoni G, Stepanyan M, Bonifacio S, Sesti F. Isobaric gasless laparoscopic myomectomy for removal of large uterine leiomyomas. Surg Endosc 2006;20:1406–9. [14] Yoon HJ, Kyung MS, Jung US, et al. Laparoscopic myomectomy for large myomas. J Kor Med Sci 2007;22:706–12. [15] Seracchioli R, Rossi S, Govoni F, et al. Fertility and obstetric outcome after laparoscopic myomectomy of large myomata: a randomized comparison with abdominal myomectomy. Hum Reprod 2000;15:2663–8. [16] American Psychiatric Association. Diagnostic and Statistical Manual of Mental disorders, 4th ed., Washington, DC: American Psychiatric Association; 1994. [17] Spitzer RL, Williams JBW, Gibbon M, Willams JBM. Structured Clinical Interview for DSM-IV Axis I Disorders (SCID), Clinician Version: User’s Guide. Washington DC: American Psychiatric Association Press; 1996. [18] Zullo F, Pellicano M, De Stefano R, Zupi E, Mastrantonio P. A prospective randomized study to evaluate leuprolide acetate treatment before laparoscopic myomectomy: efficacy and ultrasonographic predictors. Am J Obstet Gynecol 1998;178:108–12. [19] Zullo F, Palomba S, Corea D, et al. Bupivacaine plus epinephrine for laparoscopic myomectomy: a randomized placebo-controlled trial. Obstet Gynecol 2004;104:243–9. [20] Vassiliou MC, Feldman LS, Andrew CG, et al. A global assessment tool for evaluation of intraoperative laparoscopic skills. Am J Surg 2005;190:107–13. [21] Walker CL, Stewart EA. Uterine fibroids: the elephant in the room. Science 2005;308:1589–92. [22] Nezhat C, Nezhat F, Bess O. Laparoscopically assisted myomectomy: a report of a new technique in 57 cases. Intl J Fertil Menop Stud 1994;39:39–44. [23] Pelosi II MA, Pelosi III MA. Pelosi minilaparotomy hysterectomy: a nonendoscopic minimally invasive alternative to laparoscopy and laparotomy. Surg Technol Int 2004;13:157–67. [24] Palomba S, Zupi E, Falbo A, et al. A multicenter randomized, controlled study comparing laparoscopic versus minilaparotomic myomectomy: short-term outcomes. Fertil Steril 2007;88:942–51. [25] Goldberg JM, Falcone T, Amundson B, Bradley L. Laparoscopic assisted versus abdominal myomectomy. Fertil Steril 1999;71(Suppl. 1):8S.
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
A randomized, controlled study comparing minilaparotomy versus isobaric gasless laparoscopic assisted minilaparotomy myomectomy for removal of large uterine myomas: Short-term outcomes Jie Tan a, Yangyan Sun a, Baoliang Zhong b, Huihua Dai c, Daoyuan Wang a,d,* a
Department of Gynaecology, Jiangyin Hospital, Medical School of Southeast of China University, No. 35 East of Renming Road, Jiangyin City, Jiangsu Province 214400, PR China School of Public Health, Peking University, No. 38 Xueyuan Road, Beijing 100083, PR China Department of Gynaecology, Jiangsu People Hospital, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing City, Jiangsu Province 210029, PR China d AmMed Cancer Center, Shanghai Ruijin Hospital, Medical School of Shanghai Jiaotong University, Shanghai 200025, PR China b c
A R T I C L E I N F O
A B S T R A C T
Article history: Received 9 April 2008 Received in revised form 2 March 2009 Accepted 12 April 2009
Objective: To compare the operative data and early postoperative outcomes for myomectomy performed by minilaparotomy (MLT) with isobaric laparoscopic assisted minilaparotomy myomectomy (LM) in a series of patients with large uterine myomas (5 cm) randomly assigned to each surgical technique. Study design: 80 patients were randomized blindly using a computer randomization list to MLT (n = 40) or LM (n = 40). Results: The mean (SD) operating time was significantly shorter after LM than after MLT (75.50 25.70 vs 96.00 26.20 min; p < 0.01). Intraoperative blood loss was less with LM (72.15 44.00 vs 96.21 38.50 ml; p < 0.05), and DHb was less with LM (1.21 0.55 vs 1.64 0.57; p < 0.05). No intraoperative complications occurred, and no case was returned to the theater in either group. No conversion to standard laparotomy was necessary. Hospitalization was shorter after LM than after MLT (4.30 1.20 vs 6.90 2.70 days; p < 0.01). Postoperative ileus was shorter after LM than after MLT (26.20 4.20 vs 40.50 4.90 h; p < 0.01). The mean VAS score at 12 h for abdominal pain was 5.5 0.7 in the LM group and 5.2 0.8 in MLT group (p < 0.05), whereas it was analogous in the two groups at 24 h, and at 48 h was 3.4 1.1 in the LM group and 4.2 1.1 in the MLT group (p < 0.05), and no difference between two groups was detected in the overall mean (at 12, 24 and 48 h). Conclusions: Several surgical and immediate postoperative outcomes were significantly better in the LM group than in the MLT group. Crown Copyright ß 2009 Published by Elsevier Ireland Ltd. All rights reserved.
Keywords: Uterine myomas Isobaric gasless laparoscopy Minilaparotomy Laparoscopic assisted minilaparotomy Myomectomy
1. Introduction Myomectomy is advisable for women who wish to preserve their childbearing capabilities, and it is needed when myomas are either asymptomatic, but growing rapidly and causing infertility/recurrent abortion, or symptomatic, causing abnormal uterine bleeding or pain [1–3]. Laparoscopy has developed into an effective tool that facilitates a wide range of pelvic surgery, including conservative myomectomy. The most common motive for conservative myomectomy, and hence laparoscopic myomectomy, is the patient’s will to avoid hysterectomy for personal reasons, or conserve fertility. Among the minimally invasive approaches to myomectomy, isobaric gasless laparoscopy (LA), using an abdominal wall-lifting
* Corresponding author at: Department of Gynaecology, Jiangyin Hospital, Medical School of Southeast of China University, No. 35 East of Renming Road, Jiangyin City, Jiangsu Province 214400, PR China. Tel.: +86 21 6270 4900; fax: +86 21 6270 4942. E-mail address: [email protected] (D. Wang).
device [4,5], minilaparotomy (MLT) [6–8] and laparoscopically assisted minilaparotomy (LM) [9] have been introduced recently. It is reported that myomectomy by isobaric gasless laparoscopy is feasible and safe, and it appears to offer several advantages over conventional laparoscopy with pneumoperitoneum [10,11]. Myomectomy via minilaparotomy has proved to be a safe and effective minimally invasive approach to myomectomy. Early discharge and return to normal activities were comparable with those for conventional laparoscopy, and the approach is far more cost effective [8]. There are two prospective trials in the literature comparing myomectomy with MLT and conventional LA using CO2 [12,13]: one compares MLT with isobaric gasless LA myomectomy and the other compares laparotomy (LT), MLT with LM. There are several studies of laparoscopic myomectomy for large myomas [4,11,14] or comparing it with abdominal myomectomy [15]. However, no study compares MLT with LM myomectomy for removal of large uterine leisomyomas. We undertook a randomized study comparing the operative data and early postoperative outcome for myomectomy performed
0301-2115/$ – see front matter . Crown Copyright ß 2009 Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2009.04.015
J. Tan et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 145 (2009) 104–108
by MLT compared with those by LM in a series of patients with large uterine leiomyomas (5 cm) randomly assigned to each surgical technique. 2. Materials and methods 2.1. Equipment and apparatus A video electronic laparoscope (Japan Olympus Co., Tokyo, Japan) and gasless lifting device and surgical apparatus (Japan Daoke Co., Tokyo, Japan) were used. 2.2. Patient selection The trial was performed in the Department of Gynaecology, Jiangyin Hospital, affiliated to Southeast of China University, Jiangsu Province, China. The study was previously approved by the local ethics committee. There was no financial interest or any arrangement with the companies producing the instruments used in the study or with competitor companies. There also was no direct payment to the authors from any source for the purpose of financing the writing of the manuscript, nor were there any other financial connections, direct or indirect, or other situations that might raise the question of bias in the work. From January 2005 to July 2007, all women with symptomatic uterine myomas requiring myomectomy were considered eligible for the study. The criteria for inclusion in the study specified the presence of one to three symptomatic intramural or subserosal myomas (without pedicle) associated with either infertility or fast growth and having a diameter of 5–10 cm.
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Major medical conditions, psychiatric disorders, current or past history of acute or chronic physical illness, premenstrual syndrome [16,17], current or past (a washout period of at least 6 months was considered appropriate before enrolment) use of hormonal drugs or drugs influencing cognition, vigilance, or mood, inability to complete the daily diary, and a history of alcohol abuse were all considered exclusion criteria. In addition, the following specific exclusion criteria were included: no desire to conceive, hypoechoic or calcified leiomyomas diagnosed at ultrasound [18], presence of submucosal leiomyomas or alterations of the uterine cavity screened by hysteroscopy and of other uterine or adnexal abnormalities at ultrasound (e.g., adenomyosis, abnormal endometrial thickness), pattern of hyperplasia with cytological atypia in the endometrial biopsy performed for abnormal uterine bleeding under hysteroscopy on suspected areas, an abnormal Papanicolau smear, and a positive urine pregnancy test. Lastly, symptomatic women who had not had a previous conception resulting in a live baby or with tubal/male factor subfertility were also excluded. Of the 109 women requiring myomectomy, 91 fulfilled the inclusion criteria and were recruited for the trial. 11 refused to participate. Written informed consent was obtained from each patient before randomization. The enrolment was closed when 80 patients were included, and 40 patients were allocated to each group (Fig. 1). 2.3. Study design At study entry, age, parity, and body mass index (BMI), leiomyoma-related symptoms, previous laparotomies, and asso-
Fig. 1. Flow diagram.
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ciated medical conditions were assessed in each patient by the same clinician. All ultrasound examinations were performed transvaginally by an experienced operator, who assessed the presence/absence of associated pelvic diseases and evaluated uterine diameters, and myoma number, diameter and location. At study entry, a sample of venous blood was obtained from each patient between 8 and 9 am, after an overnight fast and bed rest during the early proliferative phase (second to third day of the cycle) to evaluate a complete blood count. Each woman gave her informed consent to be included into the study, which was previously approved by the local ethics committee. After enrolment by a physician, each woman had concealed randomization by a nurse to MLT (n = 40) or LM (n = 40), in a closed and dark-colored envelope until surgeries were assigned (before entering the operating room), using a computer-generated list of randomization. Thus, patients were assigned to one of the two surgical procedure groups (i.e., MLT or LM). All procedures were performed by the same surgeon (Dr. Ji Tan, M.D., who is equally experienced in both procedures) using the same technique. During each surgical procedure, total operative time, specifically the total duration of the surgical procedure, was calculated during the MLT or LM procedure beginning from abdominal skin incision, before Verres needle insertion, to skin suture.Intraoperative blood loss and intraoperative and postoperative complications were also evaluated and recorded in both groups. The intraoperative blood loss was differentially expressed as the difference between aspirated and irrigated liquid, and as the hemoglobin level decrease (DHb). Intraoperative complications were defined as laparotomic conversions and as bowel, bladder, ureteral, or vascular injuries. Laparotomic conversions were defined as open abdominal access through a more than 7-cm long skin incision. After intervention all patients received an intravenous bolus of tramadol (100 mg), followed by patient-controlled analgesia (tramadol 200 mg [2 vials] in 500 ml of saline solution) [19]. The postoperative analgesia was administered during the first 12 h after surgery. At the end of the surgical procedure the postoperative pain was also evaluated using VAS. The VAS consisted of a non-graduated 10 cm line ranging from ‘no pain’ to ‘pain as bad as it could be’ [20]. Postoperative pain was specifically assessed in each group at 0 h, 12 h, 24 h and 48 h after the surgical procedure. A blood sample was obtained and DHb was calculated for each woman 24 h after surgery. Durations of postoperative ileus and hospitalization were evaluated in both groups. Hospitalization time was defined from entry (the day of surgery) to discharge. 2.4. Surgical procedures All procedures were performed by the same surgeon (Jie Tan, MD, who was equally experienced in both procedures) using the same technique. The operator was informed of the type of intervention to be performed (whether MLT or LM) just before entering the operating room. Those assessing the outcome measures were blinded to the group assignment. A drug for thrombosis prophylaxis was not administered to any patient. After anesthesia administration, each patient was placed in a modified lithotomic position. Immediately before surgery, each patient received 2 g of IV cephalosporin as antibiotic prophylaxis, and if necessary, the same dose was repeated if the intervention lasted more than 2 h. In the LM group, a 10-mm port was inserted through the umbilicus to introduce the laparoscope, which was connected to a camera for video monitoring. An accessory 5-mm trocar was inserted into the abdomen to the left of the umbilicus. The video camera was used to identify the myoma and to obtain visual guidance for the insertion of the corkscrew through the peritoneum. The accessory trocar was used to insert operative instruments and the suction irrigation cannula. At the same time,
the minilaparotomic incision was performed. Minilaparotomy was performed with a 4- to 7-cm suprapubic incision. In the MLT group, procedures were performed without laparoscopic assistance. To avoid accidental extension of the minilaparotomies two double sutures were made at the ends of the skin incisions. The length and the distance from pubic symphysis of the skin incision varied according to leiomyoma diameter and localization. In both groups (MLT and LM), the uterine incision was performed using the same electrosurgical device with a cutting current of 70W. At the end of each intervention, the pelvis was washed with saline solution. No adhesion barrier or saline dextran macromolecular solutions were left in the peritoneal cavity. All operative samples were submitted for pathologic examination. 2.5. Statistical analysis At the study design, we considered the primary and secondary outcomes of the trial as intraoperative blood loss and postoperative abdominal pain VAS scores, respectively. For sample size calculation, we referred to the data of our clinical practice of seven cases for each procedure. A power calculation verified that 40 patients in each group would be necessary to detect a difference with an alpha error level of 5% and a beta error of 80%. Statistical analysis was performed using the Statistical Program/SPSS for Windows, version 11.5 (Chicago, IL, USA). Continuous outcome variables were analyzed using Student’s t-test. Discrete variables were analyzed with the chi-square test or Fisher’s exact test. The modification in the time observed in the both groups were compared by Analysis of Variance (ANOVA) for repeated measures. A p-value less than 0.05 was considered statistically significant. 3. Results Figure 1 illustrates the flow diagram of the present clinical study. The two groups of 40 patients each were obtained from randomization of 80 patients. No difference was observed between the two groups in uterine size, diameter of leiomyomas, main diameter of the largest leiomyoma, and number of leiomyomas, and the localization of leiomyomas was also similarly distributed in the two groups (Table 1). In all cases the estimated size and the histologic leiomyoma diagnosis, suspected before surgery through ultrasound, were confirmed, respectively, by macroscopic and microscopic examination of the enucleated tumors. Procedures were successfully performed for all the patients in both groups. The mean operating time was significantly shorter after LM than after MLT (76.4 20.7 vs 89.7 25.5 min; p = 0.012). Intraoperative blood loss was less with LM (79.9 12.9 vs 96.0 27.3 ml; p = 0.001), and DHb was less with LM (1.3 0.6 vs 1.6 0.6; p = 0.007) (Table 2). No intraoperative complications occurred, and no case was returned to the theater in either group. No conversion to standard laparotomy was necessary. With regard to the early postoperative outcome, no difference between two groups was detected in hospitalization days (1.8 0.5 vs 2.0 0.6 days; p = 0.194) and postoperative ileus (23.1 4.6 vs 22.9 4.2 h; p = 0.826) (Table 3). The repeated measures analysis of variance on postoperative abdominal pain VAS scores found that there was no difference of the VAS score among the four time points (0, 12 h, 24 h and 48 h), with the two groups combined (F = 852.726, p < 0.001); and no difference was found in the VAS score between the treatment groups, with values at all time points averaged and over time (p > 0.05) (Table 4). 4. Discussion The standard treatment of uterine fibroids – surgical excision and hysterectomy – has been promulgated as the one-size-fits-all
J. Tan et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 145 (2009) 104–108 Table 1 Main characteristics of the two study groups.
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Table 3 Early postoperative outcomes in the MLT and LA–MLT groups.
Group
MLT (n = 40)
LA–MLT (n = 40)
p-Value
Group
MLT (n = 40)
LA–MLT (n = 40)
p-Value
Age (years)a BMI (kg/m2)b Indication for myomectomy (n, %) Menstrual disorders Pelvic pain Unexplained infertility Rapidly grown myoma Previous major abdominal surgery (n, %) None One operation More than one operation Dominant myoma diameter (cm)a Proportion of patients according to number of myomas (n, %) <3 3 Dominant myoma (location): (n, %) Intramural Subserosal Dominant myoma (site): (n, %) Posterior Anterior Fundal
36.3 2.5 22.8 2.0
35.8 3.4 23.0 2.0
0.432 0.611 0.939
Postoperative ileus (h)a Hospitalization (days)a Conversion to laparotomy: n
23.1 4.6 1.8 0.5 0
22.9 4.2 2.0 0.6 0
0.826 0.194 NS
15 5 18 2
14 6 19 1
(37.5) (12.5) (45.0) (5.0)
a
(35.0) (15.0) (47.5) (2.5) 0.500
31 (77.5) 6 (15.0) 3 (7.5) 8.2 1.5
32 (80.0) 4 (10.0) 4 (10.0) 7.7 1.4
0.116 0.617
28 (70.0) 12 (30.0)
30 (75.0) 10 (25.0) 0.816
14 (35.0) 26 (65.0)
15 (37.5) 25 (62.5) 0.896
16 (40.0) 17 (42.5) 7 (17.5)
15 (37.5) 19 (47.5) 6 (15.0)
Some differences between groups were compared with Fisher’s exact Test method. Some cells with expected count less than 5 were merged in neighboring cells. a Values are expressed as mean standard deviation. There were no significant differences between the groups. b BMI, body mass index.
solution [21]. However, myomectomy is advisable for women who wish to preserve their childbearing capabilities, and it is needed when myomas are either asymptomatic, but growing rapidly and causing infertility/recurrent abortion, or symptomatic, causing abnormal uterine bleeding or pain [2,3]. The use of minilaparotomy in surgery for benign gynecologic disease has been well established [6]. Laparoscopic assisted myomectomy was first reported in 1994 [22]. In their review of 57 cases, the authors concluded that the procedure is far easier to teach than laparoscopic myomectomy because of the high degree of technical skill required for the latter. Similarly, myomectomy via minilaparotomy was shown to be a safe and effective minimally invasive approach with little bleeding, few complications, and early discharge and return to normal activities [6,7,8,23]. In a multicenter randomized, controlled study, Palomba et al. confirmed that minilaparotomic myomectomy is related to a lower global degree of surgical difficulty, and that it is a highly feasible and safe procedure, even if the laparoscopic approach remains, in expert hands, the procedure better related to the best short-term outcomes [24]. In two retrospective non-randomized studies, LM induced a similar blood loss, but fewer days of hospitalization, fewer days to
Table 2 Main operative parameters in the MLT and LA–MLT groups. Group
MLT (n = 40)
LA–MLT (n = 40)
p-Value
Total operative time (min)a Intraoperative blood loss (ml)a DHba
89.7 25.5 96.0 27.3 1.6 0.6
76.4 20.7 79.9 12.9 1.3 0.6
0.012 0.001 0.007
a
Values are expressed as mean standard deviation. Hb, haemoglobin.
Values are expressed as mean standard deviation. NS, not significant.
resume normal activity [21,25] and less postoperative use of analgesics [25]. The first randomized study reported that MLT and LM offer advantages in comparison with classic laparotomy [9]. To our knowledge, there are two prospective trials in the literature comparing myomectomy with MLT and conventional LM using CO2 [12,13]: one study compares MLT with isobaric gasless LA myomectomy and the other compares laparotomy (LA), MLT with LM. However, no study compares MLT with LM for removal of large uterine leisomyomas, although there are several studies of laparoscopic myomectomy for large myomas [4,11,14], or comparing it with abdominal myomectomy [15]. We undertook this randomized study comparing the operative data and early postoperative outcomes for myomectomy performed by LM compared with those by MLT in a series of patients with large uterine leiomyomas (5 cm) randomly assigned to each surgical technique. In our study, the operation was completed for all the patients using a minimally invasive approach (MLT or LM), and no conversion to standard laparotomy was necessary. No case in either group was returned to the operative theater. There was only difference of the VAS score among the four time points (0 h, 12 h, 24 h and 48 h) with the MLT and LM groups combined; and no difference the VAS score between the treatment groups, with values at all time points averaged and over time. Myomectomy for removal of large uterine myomas by LM is more feasible than by MLT [8]. It allows an accurate uterine repair. In particular, LM furnishes a more accurate cleaning of the pelvic cavity because after peritoneal closure, homeostasis is further controlled under videolaparoscopy, and repeated washings are performed for complete debris removal. LM allows clear vision of the pelvic cavity and furnishes visual guidance to the transperitoneal insertion of the corkscrew manipulator into the myoma, so that the operating time is clearly shorter with LM and intraoperative blood loss and DHb were less with LM. In this study a 4- to 7-cm transverse incision was performed for minilaparotomic access whereas there is not a standard universally accepted definition of ‘minilaparotomy’ used to compare correctly the results of the different studies. Pelosi et al. consider a laparotomy to be ‘mini’ with an incision of 2.5–5 cm [23], whereas
Table 4 The results of repeated measures analysis of variance on postoperative abdominal pain VAS scores. Group
At At At At a
0 ha 12 ha 24 ha 48 ha
MLT (n = 40)
LA–MLT (n = 40)
Treatment effect
8.4 1.2 5.0 0.7 4.3 1.1 4.1 0.7
8.0 1.0 5.3 0.6 4.2 0.9 3.4 0.6
0.079
p-Value* Effect of time
Interaction between treatment and time
<0.001
0.139
Values are expressed as mean standard deviation. The treatment effect denotes the difference between the treatment groups, with values at all time points averaged; the effect of time denotes differences among the three time points, with the two groups combined; and the interaction between treatment and time denotes the difference between the two groups over time. *
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others give longer incision sizes, from 3 to 6 cm [8] up to less than 10 cm [6,10]. In conclusion, our results demonstrate that isobaric gasless LM and MLT can be a suitable option in uterine myomectomy. Several surgical and immediate postoperative outcomes were significantly better in the gasless LM group than in the MLT group. However, multi-center prospective randomized studies are required to confirm the results of this study, and to compare early and late clinical outcome of myomectomy by MLT with that performed by LM, including but not limited to: recurrence rate, fertility and obstetric outcome. References [1] Stewart EA. Uterine fibroids. Lancet 2001;357:293–8. [2] Vollenhoven BJ, Lawrence AS, Healy DL. Uterine fibroids: a clinical review. Br J Obstet Gynecol 1990;97:285–98. [3] Donnez J, Mathieu PE, Bassil S, Smets M, Nisolle M, Berliere M. Fibroids: management and treatment: the state of the art. Hum Reprod 1996;11:1837– 40. [4] Chang FH, Soong YK, Cheng PJ, et al. Laparoscopic myomectomy of large symptomatic leiomyoma using airlift gasless laparoscopy: a preliminary report. Hum Reprod 1996;11:1427–32. [5] Damiani A, Melgrati L, Marziali M, Sesti F. Gasless laparoscopic myomectomy: indications, surgical technique, and advantages of a new procedure for removing uterine leiomyomas. J Reprod Med 2003;48:792–8. [6] Benedetti-Panici P, Maneschi F, Cutillo G, Scambia G, Congiu M, Mancuso S. Surgery by minilaparotomy in benign gynecologic disease. Obstet Gynecol 1996;87:456–9. [7] Fanfani F, Fagotti A, Longo R, Marana E, Mancuso S, Scambia G. Minilaparotomy in the management of benign gynecologic disease. Eur J Obstet Gynecol Reprod Biol 2005;119:232–6. [8] Glasser MH. Minilaparotomy myomectomy: a minimally invasive alternative for the large fibroid uterus. J Minim Invasive Gynecol 2005;12:275–83. [9] Cagnacci F, Pirillo D, Malmusi S, Arangino S, Alessandrini C, Volpe A. Early outcome of myomectomy by laparotomy, minilaparotomy and laparoscopically assisted minilaparotomy. A randomized prospective study. Hum Reprod 2003;18:2590–4.
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