Randomized study of laparoscopic versus minilaparotomic myomectomy for uterine myomas

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1 Journal of Minimally Invasive Gynecology ( , Original articles Randomized study of laparoscopic versus minilaparotomic myomectomy for uterine myomas Franco Alessandri, MD, Davide Lijoi, MD, Emanuela Mistrangelo, MD, Simone Ferrero, MD, and Nicola Ragni, MD From the Department of Obstetrics and Gynecology, San Martino Hospital and University of Genoa, Largo R. Benzi 10, 16132, Genoa, Italy (all authors. KEYWORDS: Laparoscopy; Minilaparotomy; Myoma; Myomectomy Abstract STUDY OBJECTIVE: To compare the postoperative recovery of patients undergoing laparoscopic and minilaparotomic myomectomy. DESIGN: Randomized study (Canadian Task Force classification I. SETTING: University hospital. PATIENTS: One hundred forty-eight women requiring surgical myomectomy. INTERVENTIONS: Myomectomy by minilaparotomy or laparoscopy. MEASUREMENTS AND MAIN RESULTS: Operation time was significantly lower in the minilaparotomy group (p.001. When compared with minilaparotomy, laparoscopy was associated with a lower decline of hemoglobin concentration (p.001, a reduced length of postoperative ileus (p.001, and a shorter time to discharge (p.001. Pain intensity at 6 hours after surgery was significantly lower in the laparoscopy group (p.001; also, patients who underwent laparoscopy requested analgesics less frequently in the first 48 hours after the operation (p.001. Patients included in the laparoscopy group were fully recuperated on postoperative day 15 more frequently than those included in the minilaparotomy group (p.012. No complications were observed in the minilaparotomy group. There were two complications in the laparoscopy group (one laparoconversion caused by difficulties of hemostasis and one acute diffuse peritonitis caused by ileal perforation. Laparoscopic and minilaparotomic myomectomy cost, respectively, 2250 euros and 1975 euros. CONCLUSION: When compared with minilaparotomic myomectomy, laparoscopic myomectomy may offer the benefits of lower postoperative analgesic use and faster postoperative recovery AAGL. All rights reserved. Uterine myomas are the most common uterine neoplasm 1 and are diagnosed in about 25% to 30% of women. Moreover, 10% to 15% of women between the ages of 25 and 64 years require hysterectomy for myomas, with a peak incidence around age 45 years. 1 Corresponding author: Simone Ferrero, MD, Department of Obstetrics and Gynaecology, San Martino Hospital, University of Genoa, Largo R. Benzi 1, Genoa, Italy. simone.ferrero@fastwebnet.it Submitted July 9, Accepted for publication November 19, Uterine myomas may be asymptomatic; however, they often are the cause of abnormal uterine bleeding, pelvic pain, infertility, and miscarriage. Until the 1950s, abdominal hysterectomy was the most common treatment used for this disorder, particularly in women beyond reproductive age. In recent years, the remarkable social and cultural changes, as well as the widespread use of contraceptives, have led to a delay in pregnancy onset; therefore uterine preservation may be required when symptomatic myomas are diagnosed during the reproductive era /$ -see front matter 2006 AAGL. All rights reserved. doi: /j.jmig

2 Alessandri et al Laparoscopic myomectomy 93 ELIGIBLE PATIENTS (n = 358 D E C L I N I N G T O PART I C I P A T E ( n = 210 R A N D O M I Z A T I O N ( n = 148 Figure 1 L A P A R O S C O P I C M I N I L A P A R O T O M I C M Y O M E C T O M Y M Y O M E C T O M Y ( n = 74 ( n = 74 Flow diagram of selection of study population. Enthusiastically described since as the gold standard for conservative pelvic surgery, myomectomy is advisable for women who wish to preserve their childbearing potential. 3 Abdominal myomectomy is associated with an acceptable morbidity rate, comparable to that of hysterectomy. The introduction of minimally invasive surgical techniques and video laparoscopy for the treatment of numerous gynecological diseases has resulted in remarkable advantages for the patient in both social and economic terms (shorter hospitalization and earlier resumption of normal activities. 4 In 1996, a study 5 proposed minilaparotomy, already adopted by general surgeons, 6,7 as a valid and costeffective alternative to laparoscopy in the treatment of benign gynecologic disease. The use of minilaparotomy in the treatment of uterine myomas has already been investigated. 8 Although abdominal myomectomy has been considered the surgical technique of choice, recent studies demonstrated that laparoscopy can be used for removing uterine myomas However, laparoscopic myomectomy can be a difficult procedure, especially for large myomas. Although several studies compared myomectomy by laparoscopy and laparotomy, the effectiveness of laparoscopic and minilaparotomic approaches in the treatment of uterine myomas has never been compared. This prospective study aimed to estimate the outcome of laparoscopic versus minilaparotomic myomectomy in patients selected by uniform criteria before random assignment to these two procedures. Materials and methods Study population Of the 358 women approached for the study from October 1, 2002, through October 31, 2004, 148 patients participated, yielding a response rate of 41.3% (Figure 1. The trial was approved by the local ethics committee. Each woman was informed of the experimental design of the study and gave informed consent to participate. All women underwent transvaginal ultrasonography in the 2 weeks before surgery. Size, location (with respect to uterine layers, position (with respect to the uterine axis, and number of myomas were evaluated and recorded. Inclusion criteria were symptomatic subserous or intramural myomas, number of myomas ranging from 1 to 4 and size of the largest myoma ranging from 3 to 7 cm. Exclusion criteria were submucosal myomas, association with ovarian or uterine lesions, age 45 years, body mass index 29, contraindications for general anesthesia, systemic infections, and psychiatric disorders precluding consent. No patient included in the study underwent medical treatment for ovarian suppression before surgery. Immediately before surgery, each woman was randomly assigned to either minilaparotomy or laparoscopy by an operating room nurse not otherwise engaged in the study. Randomization was performed by using a computer-generated randomization list drawn up by a statistician. Wounds and site ports were dressed with identical dressings regardless of surgical procedure; therefore, during the hospital stay, the patients were unaware of the procedure performed. Surgical procedures All surgical procedures were performed by the same investigator of consultant grade (F.A. who has extensive experience in both laparoscopic and laparotomic surgery. The surgical procedures were performed with the patients under general anesthesia that was induced by use of propofol 2.5 mg/kg atracurium 0.5 mg/kg fentanyl 0.05 mg. During surgery, anesthesia was maintained with atracurium 0.01 mg/kg/30 min remifentanil g/kg/min sevoflurane 1 minimum alveolar concentration (MAC; 60% air, 40% O 2.

3 94 Journal of Minimally Invasive Gynecology, Vol 13, No 2, March/April 2006 Minilaparotomy was performed with a suprapubic transverse incision 4 to 6 cm in length, the difference in the size of the incision was related to the number, size, and position of the myomas and to the presence of central obesity. The subcutaneous fat and abdominal fascia were opened crosswise, and the abdominal muscle was opened longitudinally on the midline. The parietal peritoneum was visualized, and it was opened longitudinally to reach the pelvic cavity. A linear uterine incision, as small as possible, was made on the most prominent part of the myoma. After identification of the myoma pseudocapsule, enucleation was possible following the cleavage plane. The uterine defects were closed with interrupted sutures of Vicryl 1 polyglactin 910 (Ethicon SpA, Rome, Italy. An open-laparoscopy technique was used for laparoscopy, and a 10-mm port was inserted through the umbilicus to introduce the laparoscope. A pneumoperitoneum was obtained with carbon dioxide insufflation. One 5-mm port (surgeon s side and one 10-mm port (contralateral side were inserted for the introduction of the surgical instruments. A uterine manipulator was used to permit antevertion, lateral uterine movements and organ exposure. After the pelvic organs were explored, an incision was made through the uterine wall and the pseudocapsule of the myoma. The myoma was then fixed with a Manhes grasping forceps (Karl Storz, Tuttlingen, Germany, and the cleavage plane between the tumor and the uterus was dissected by coagulating and cutting connective tissue bridges. Traction on the myoma, combined with antevertion and lateral uterine movements, facilitated dissection. All uterine defects were closed with interrupted sutures of Vicryl 1-0 (Ethicon SpA with intracorporeal knots. The myomas were removed by use of a Steiner automatic morcellator (Karl Storz. Postoperative symptoms assessment At the end of surgical procedures, all patients received tramadol (100 mg and ketorolac tromethamine (30 mg intravenously. Postoperative pain intensity was determined at 6 hours after surgery by use of a 100-mm visual analogue scale (VAS; the left extreme represented the absence of pain, and the right extreme represented the worst possible pain. No patient included in the study systematically received analgesics in the 8 hours after surgery. In both groups, postoperative analgesics (intramuscular ketorolac, 30 mg were given when requested by the patient. When patients did not request analgesic therapy, the intensity of postoperative pain was measured again at 20 hours after surgery. Consumption of analgesics was evaluated by comparing the proportion of patients who required analgesics on day 2 in the 2 groups. The length of postoperative ileus was evaluated by asking the patients when they recovered the ability to pass gas. The hemoglobin decline was determined 24 hours after surgery. Before hospital discharge, patients had to tolerate a normal diet, be able to dress themselves, be fully mobile around the ward, be analgesic free, and be satisfied that they could manage at home. The length of postoperative hospital stay, in term of hours of hospitalization after surgery, was noted. Postoperative subjects were reviewed at the outpatient clinic at 15 days. They were asked about return to everyday activity and work; recovery was evaluated by comparing the proportion of patients feeling fully recuperated on day 15 in the 2 groups. At 6 months after surgery, all patients underwent transvaginal ultrasonography, and symptom recurrence was determined. Statistical analysis Data were analyzed by use of Student s t test, the Mann-Whitney U test, 2 testing, and the Fisher exact test. Continuous parametric variables were expressed as mean ( standard deviation; nonparametric variables were expressed as median and range. Confidence intervals were calculated for categorical data. All calculations were performed with the SPSS software package (release ; SPSS Inc, Chicago, Ill. A p value of.05 was considered statistically significant. Results Randomization produced 2 groups with similar characteristics; mean age, body mass index, and characteristics of the myomas were similar in the 2 groups (Table 1. No complications were observed in the minilaparotomy group. There were 2 complications in the laparoscopy group: 1 laparoconversion, caused by difficulties of hemostasis, and 1 case of acute diffuse peritonitis caused by ileal perforation, presumably caused by monoterminal coagulation of bowel adhesions. This last case required a laparotomy 10 days after laparoscopic myomectomy; the peritoneal cavity was washed and adequately drained. These 2 patients were excluded from the analysis. Operation time was significantly lower in the minilaparotomy group (p.001. Both the procedures were associated with a decline of hemoglobin concentration, but the net hemoglobin decline observed 24 hours after laparoscopy was significantly smaller than that observed after minilaparotomy (p.001; no blood transfusion was required in the 2 groups. The time of postoperative ileus and time to discharge were significantly lower after laparoscopy than minilaparotomy (p.001. Pain intensity at 6 hours after surgery was significantly lower in the laparoscopy group than in the minilaparotomy group (p.001; this observation is in line with the fact that, in the first 48 hours after the operation, 33.8% of the patients who underwent laparoscopy and 73.0% of the patients who underwent minilaparotomy requested analgesics (p.001. Patients included in the laparoscopy group were fully recuperated on postopera-

4 Alessandri et al Laparoscopic myomectomy 95 Table 1 Baseline characteristics of the study population Minilaparotomy Laparoscopy p Value Number of patients (n Age (years; mean SD Body mass Index (kg/m 2 ; mean SD Parity (n; median, range 1 (0-4 1 ( Main indications for myomectomy (n.833 Abnormal uterine bleeding Infertility Abortion 13 9 Pain Growing rapidly 7 5 Number of myomas (n; mean SD Mean diameter of the largest myoma (cm; mean SD Weight of the myomas removed from each patient (g; mean SD tive day 15 more frequently than those included in the minilaparotomy group (Table 2. At 6 months after surgery no myoma recurrence was observed at transvaginal ultrasonography; no patient reported symptom recurrence. In our institute, the mean cost of the equipment for each pure surgical treatment performed by laparoscopy was 650 euros versus 270 euros when it was performed by minilaparotomy; in addition, about 500 euros per hour were spent for surgeons, anesthetists, nurses, and maintenance of the operative room. The cost of the hospital stay was about 500 euros per day. Therefore each laparoscopic myomectomy costs 2257 euros, and each minilaparotomic myomectomy costs 1975 euros. Concerning laparoscopic myomectomy, conversion to laparotomy was required in 1 case, and subsequent surgery was necessary in another patient, therefore additional costs in our series were 3020 euros; as a result, the mean cost of laparoscopic myomectomy was 2330 euros. Discussion In the past, some randomized trials demonstrated the benefits of laparoscopic versus abdominal myomectomy 13 and of minilaparotomic versus abdominal myomectomy. 8 One study 13 demonstrated that, in women with a mean number of 2.4 myomas and a mean larger myoma size of 4 cm, laparoscopy reduces postoperative pain, time of discharge, and time of recovery when compared with abdominal myomectomy. Similar results on time of discharge were reported in another study, 14 in which the mean number of myomas was 2.7 and the maximal myoma size was 7 cm. However, not all surgeons are comfortable with laparoscopic myomectomy and uterine repair. Minilaparotomy has been proposed to maintain the efficacy of uterine repair and to reduce the clinical impact of myomectomy by laparotomy. 6,8 To the best of our knowledge, this is the first randomized study aiming at analyzing the differences between laparo- Table 2 Comparison between minilaparotomy and laparoscopy Minilaparotomy (n 74 Laparoscopy (n 72 p Value Operation time (min; mean SD Decline of hemoglobin concentration (g/dl; mean SD Pain intensity in the whole study group at hours after surgery (on a 10 mm VAS scale; mean SD Pain intensity in patients not requesting (n (n analgesics at 24 hours after surgery (on a 10 mm VAS scale; mean SD Request of analgesic (n; %, 95% confidence 54 (73.0%, 61.4%-82.6% 25 (34.7%, 23.9%-46.9%.001 interval Time of postoperative ileus (hours; mean SD Time to discharge (hours; mean SD Patients fully recuperated on day 15 (n; %, 95% confidence interval 55 (74.3%, 62.8%-83.8% 65 (90.3%, 81.0%-96.0%.012

5 96 Journal of Minimally Invasive Gynecology, Vol 13, No 2, March/April 2006 scopic and minilaparotomic myomectomy on the postoperative recovery. Many authors demonstrated the substantial benefits in terms of reduced postoperative pain, shorter hospital stay, and faster recovery of operative laparoscopy versus abdominal surgery for both ectopic pregnancy 12 and endometriosis-associated infertility. 16 Similar results were observed for laparoscopic versus abdominal myomectomy. 13,14,17 In this study, laparoscopy was associated with a lower decline of hemoglobin concentration, a shorter time of postoperative ileus, a lower postoperative analgesic use, and a reduced time of discharge when compared with minilaparotomy. In addition, pain intensity at 6 hours after surgery was significantly lower among women undergoing laparoscopic myomectomy than in those who underwent minilaparotomy. Finally, patients treated by laparoscopy returned to normal activity sooner than subjects treated by minilaparotomy (Table 2. Laparoscopic approach was more expensive than minilaparotomy, particularly when the management of complications was considered. However, shorter hospital stay, faster recovery, and faster return to work are advantages for the patient that may lead to economic benefits also for the community. These economic advantages have been previously demonstrated for several laparoscopic procedures when compared with laparotomy 12,16 and minilaparotomy. 18 The 6-month follow-up suggests that laparoscopic and minilaparotomic myomectomy have the same therapeutic effectiveness. Mais et al 13 ultrasonographically observed myoma recurrence at 180 days; they found a myoma recurrence in 2 women in the laparoscopic group and 1 in the laparotomy group (no statistical difference. Similar results in terms of myoma recurrence were observed in a recent series 17 at 2 years follow-up. The limited number of patients included in this study does not allow drawing any definitive conclusion on the safety of laparoscopic myomectomy. In our series, one small bowel injury occurred, and in one case laparoconversion was required. Many authors analyzed feasibility and complications of laparoscopic myomectomy; the conclusions of these studies are that the conversion rate to laparotomy is less than 2% and that laparoscopy is a relatively safe technique, even when large deep myomas are resected. In 2000, one group 14 reported their experience on 66 laparoscopic myomectomies in infertile women; 3 cases were converted to abdominal procedures because of difficulties of hemostasis or difficulties in suturing. Malzoni et al 19 reported 2 cases of conversion to laparotomy in a series of 144 laparoscopic myomectomy. Sinha et al 9 described a case series of 51 laparoscopic myomectomies for large myomas (9-21 cm; they had 2 complications (1 broad ligament hematoma and 1 postoperative hysterectomy and reported a particularly high postoperative transfusion rate (39.2%. In our study, no blood transfusion was required in both laparoscopic and minilaparotomic groups; laparoscopy was associated with a lower postoperative decline in hemoglobin concentration, but the difference in the hemoglobin drop between the 2 groups was of limited clinical value. Our results are similar to other randomized studies. 14 Stringer et al 20 reported a higher mean blood loss for laparoscopic myomectomies compared with laparotomic ones (340 vs 110 ml; p.001; 3 patients were transfused in the open group, compared with no transfusions in laparoscopic group. Laparoscopy is a technically challenging procedure that requires specialized instrumentation and advanced intracorporeal suturing capability. 9 Obviously, it should be considered that laparoscopic myomectomy is not feasible in all patients, and even skilled operative laparoscopists prefer laparotomy in patients with large multiple myomas. 17,21 Two studies 14,15 demonstrated that pregnancy rate after laparoscopic and laparotomic myomectomy were similar; this finding is in contrast with another study 22 showing that patients who undergo laparoscopic procedures have higher probability to conceive, possibly because of a reduced occurrence of postoperative adhesions. We are aware that one limitation of this study is the fact that it was not a double-blind study. Unfortunately, we could not perform a double-blind study because, in our hospital, the surgeons participate in the postoperative care of the patients in the ward. However, most of the findings of the study were based on objective observations that were not dependent on the ward personnel (i.e., pain measured on a VAS scale, decline of hemoglobin concentration, request of analgesics. Objective criteria (described in the Materials and Methods were used for those variables (i.e., hospital discharge that could have been more influenced by the absence of double-blinding. Conclusion In conclusion, our data suggest that when compared with minilaparotomic myomectomy, laparoscopic myomectomy may offer the benefits of lower postoperative analgesic use and faster postoperative recovery. These observations are in line with a recent extensive review 23 concluding that laparoscopic myomectomy provides an acceptable, and perhaps a preferable, alternative to abdominal myomectomy for women with symptomatic fibroids up to 7 cm, who desire uterine preservation. In fact, laparoscopic myomectomy provides a more rapid recovery and is usually associated with less blood loss and fewer adhesions compared with abdominal myomectomy. Randomized studies are required to compare the late clinical outcome of myomectomy by minilaparotomy with that performed by laparoscopy. In spite of the increasing improvements in laparoscopic instruments and techniques, advanced technical skills (particularly in intracorporeal suturing are required to perform laparoscopic myomectomy. Minilaparotomy offers a valid minimally invasive alternative for those gynecologists who

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