Service de Gynécologie, Hôpital Tenon, AP-HP, Paris, France
* Correspondence to: Professor E. Daraï, Service de Gynécologie-Obstétrique, Hôpital Tenon, 4 rue de la Chine, 75 020 Paris, France. Tel: +33-1-56-73-18; Fax: +33-1-56-01-73-17; Email: emile.darai{at}tnn.ap-hop-paris.fr
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Abstract |
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Patients and methods: In a French retrospective multicenter study of 358 women with borderline ovarian tumors, we compared epidemiological characteristics, sonographic findings, serum tumor marker levels, and surgical and histological parameters between women undergoing laparoscopy and women undergoing laparotomy.
Results: One hundred and forty-nine (41.6%) of the 358 women underwent laparoscopy. Mean age, mean gestity and parity, and mean tumor size were higher in the laparotomy group. Forty-two women (28.2%) underwent laparoconversion, mainly for suspected ovarian cancer or large tumor volume. Conservative treatment and cyst rupture were more frequent in the laparoscopy group than in the laparoconversion and laparotomy groups (P <0.0001). The rate of complete staging was lower in the laparoscopy group than in the laparoconversion and laparotomy groups (P <0.0001), with no difference between these latter two groups. No difference in the recurrence rate was noted between the groups, but a higher recurrence rate was observed after conservative treatment (P <0.001).
Conclusions: Laparoscopic management of borderline ovarian tumors is associated with a higher rate of cyst rupture and incomplete staging. Recurrence was more frequent after conservative treatment. Whatever the surgical route, the rate of complete initial staging was low, emphasizing the need to respect treatment guidelines for borderline ovarian tumors.
Key words: borderline ovarian tumor, laparoconversion, laparoscopy, laparotomy, recurrence
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Introduction |
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Laparoscopy has become the standard approach for the treatment of women with benign ovarian tumors [8, 9
]. Despite the use of imaging techniques, including transvaginal sonography and color Doppler, and serum tumor markers, it sometimes remains difficult to distinguish between benign, borderline and malignant ovarian tumors. Owing to the non-specific macroscopic aspect of borderline ovarian tumors, and the relatively poor diagnostic accuracy of intra-operative histology, borderline ovarian tumors may fail to be recognized or adequately treated during laparoscopy [10
12
].
The few available data on laparoscopic management of borderline ovarian tumors suggest that this approach is feasible and safe when oncological guidelines are respected [1315
]. In addition, Querleu et al. [16
] recently reported the feasibility of laparoscopic restaging in women treated for borderline ovarian tumors by laparoscopy or laparotomy. The main concerns regarding laparoscopic treatment of borderline ovarian tumors are the risk of inadequate initial staging, tumor cell dissemination and wound metastasis. The aims of this French multicenter study of women with borderline ovarian tumors were to compare initial laparoscopic and laparotomic management, and to assess the possible limitations of the laparoscopic approach.
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Patients and methods |
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Histological typing was performed essentially according to International Federation of Gynecology and Obstetrics (FIGO) recommendations [3]. The histological criteria used for the diagnosis of borderline tumors included: (i) stratification of the epithelial lining of the papillae, with formation of microscopic papillary projections or tufts arising from the epithelial lining of the papillae; (ii) nuclear atypia; (iii) mitotic activity; (iv) intracystic clusters of free-floating cells; and (v) the absence of stromal invasion. Patients with serous borderline ovarian tumors exhibiting micropapillary features or with mucinous borderline tumors exhibiting features of intraepithelial carcinoma were not excluded, and nor were women with microinvasion.
The choice between laparotomic and laparoscopic management was made in each participating center. Laparoconversion was recorded when laparotomy was performed for technical reasons (tumor volume, adhesions, transparietal cystectomy or salpingo-oophorectomy), suspicious tumors or the results of intra-operative histology. Women who initially underwent laparoscopy were compared with women who initially underwent laparotomy. The laparoscopic group was subdivided into women who underwent laparoconversion and women who exclusively underwent laparoscopy.
Surgery was considered conservative when at least a portion of one ovary and the uterus were spared. Conservative ovarian treatment consisted of unilateral cystectomy, unilateral salpingo-oophorectomy, unilateral salpingo-oophorectomy and contralateral cystectomy, or bilateral cystectomy. Surgery was considered non-conservative when bilateral salpingo-oophorectomy was performed. Staging was considered complete when all peritoneal surfaces were carefully inspected and peritoneal washing, multiple random or oriented biopsies, and infra-colonic omentectomy were performed. Systematic appendectomy was also a criterion for complete staging of mucinous borderline tumors. Initial staging was considered incomplete in all other cases, independently of the radical or conservative nature of treatment. A lack of pelvic and retroperitoneal lymph node dissection did not rule out complete staging, as this procedure was no longer used systematically after 1995 for staging borderline ovarian tumors.
Disease was staged as recommended by FIGO [3]. Restaging operations were surgical procedures performed after initial incomplete staging, whatever the initial stage of the disease, when (i) the interval between initial and restaging surgery was <6 months, and (ii) women received no adjuvant therapy. Restaging was done by laparotomy or laparoscopy, depending on the participating center. Women undergoing second-look surgery after complete initial staging, with or without adjuvant therapy, were excluded from the study.
The use of adjuvant chemotherapy and/or radiotherapy for women with advanced-stage disease was decided on in each participating center.
Statistical analysis
The 2-test and Student's t-test were used. P values <0.05 were considered significant.
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Results |
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Sonographic aspect of borderline ovarian tumors and preoperative serum tumor marker levels in the laparoscopy and laparotomy groups (Table 2)
Sonography was the most frequent imaging technique used to evaluate borderline ovarian tumors (62.5%), followed by computed tomography (27.8%) and magnetic resonance imaging (9.7%). Sonographic findings were available for 198 women (55.9%). The main difference in sonographic features was a larger tumor size in the laparotomy group (P <0.0001). Most borderline tumors had liquid features in both groups. No difference in the frequency of solid tumors, liquid/solid ratios >1, multilocular forms or endophytic growth was found between the groups.
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Initial surgery
Intra-operative histological examination was performed in 150 cases overall (41.9%), and in, respectively, 48 (32.2%) and 102 cases (48.8%) in the laparoscopy and laparotomy groups (P=0.04). The results of intra-operative histological examination are shown in Table 3, according to the group. Intra-operative histological examination led to the diagnosis of a borderline tumor in 97 cases (64.7%), a benign tumor in 34 cases (22.7%) and carcinoma in three cases (2%), and failed to distinguish between a borderline tumor and a malignant tumor in 16 cases (10.6%).
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Surgical procedures performed in the laparoscopy, laparoconversion and laparotomy groups are shown in Table 4. The frequency of conservative treatment differed between the three groups (P <0.0001). Conservative treatment was more frequent in the laparoscopy group than in the laparoconversion and laparotomy groups (P <0.0001). Only about two-thirds of patients underwent peritoneal washing. The three groups differed as regards the frequency of peritoneal washing (P=0.03), directed or random peritoneal biopsy (P <0.0001), omentectomy (P <0.0001) and appendectomy (P <0.0001). As a result, complete staging was less frequent in the laparoscopy group than in the laparoconversion and laparotomy groups (P <0.0001); the latter two groups did not differ in this respect. The rupture rates during cystectomy in the laparoscopy, laparoconversion and laparotomy groups were 41.8% (18 of 43), 62.5% (five of eight) and 35.7% (five of 14), respectively. The cyst rupture rate differed significantly between the laparoscopy group and the laparoconversion and laparotomy groups (P <0.0001). Moreover, cyst rupture rate was significantly higher in the laparoscopy group than the laparotomy group (P <0.001), in the laparoscopy group than laparoconversion group (P <0.01), and in the laparoconversion than laparotomy groups (P<0.001). In the laparoscopy group, protected extraction was performed in 47.6% of cases.
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Results of restaging surgery in women initially treated by laparoscopy
Thirty (28%) of the 107 women with borderline tumors who were initially treated by laparoscopy underwent a restaging operation. At initial laparoscopy, 19 (63.3%) of these 30 women underwent cystectomy, and 11 (36.7%) underwent unilateral salpingo-oophorectomy. Restaging operations were performed by laparoscopy and laparotomy in 21 and nine cases, respectively. Treatment during the restaging operation was conservative and non-conservative in 18 (60%) and 12 (40%) cases, respectively.
Six (20%) of the 30 women were upstaged. Five of them had serous borderline tumors and one a mucinous tumor. Five of the six upstaged women initially had stage Ia disease and one stage Ic disease. Among the five women with initial stage Ia disease, the final stage was Ib in two cases, IIa in one case and IIIa in two cases. The woman with initial stage Ic disease was finally at stage IIIc.
Recurrence rates according to the initial surgical approach
Mean follow-up in the laparoscopy, laparoconversion and laparotomy groups was 27.5 ± 33.6, 40 ± 41.8 and 42.4 ± 48.9 months, respectively (P <0.004). Follow-up was shorter in the laparoscopy group than in the laparoconversion group (P=0.005) and the laparotomy group (P=0.0002); no difference was found between the laparoconversion and laparotomy groups.
Thirteen recurrences (12.1%) occurred in the laparoscopy group. The mean time to recurrence was 25 ± 18.2 months. All the recurrences occurred after conservative treatment (13 of 75; 17.3%). Among the 13 recurrences, five occurred on ipsilateral ovary, seven on contralateral ovary, and the last one was observed onto pelvic peritoneum. No wound metastases were diagnosed during the study period. For the 13 recurrences, conservative and non-conservative treatment was performed in 10 and three cases, respectively. One hundred and three of 107 women were alive without disease, and four were alive with disease.
Five recurrences (11.9%) occurred in the laparoconversion group. The mean time to recurrence was 11.3 ± 9.3 months. All the recurrences occurred after conservative treatment (five of 23; 21.8%). Among the five recurrences, ipsilateral or contralateral ovarian recurrences were observed in three and two cases, respectively. For the five recurrences, conservative and non-conservative treatment was performed in two and three cases, respectively. No wound metastases were diagnosed during the study period. Thirty-three of 42 women were alive without disease, one was alive with disease and eight were lost to follow-up.
Nineteen recurrences (9.1%) occurred in the laparotomy group. The mean time to recurrence was 35.4 ± 41.1 months. Among the 19 recurrences, ipsilateral, contralateral or bilateral ovarian recurrences were observed in three, seven and one cases, respectively. In addition, seven recurrences were diagnosed onto pelvic peritoneum, and the last was on the spleen. The recurrences occurred after conservative treatment in 11 of 66 women (16.6%) and after non-conservative treatment in eight of 143 (5.6%) women. For women receiving non-conservative treatment, the eight recurrences were diagnosed by sonography in three cases, by elevated CA125 serum levels in one case, during systematic second-look surgery in three cases and during a laparotomy indicated for renal cancer in one case. Among the 19 women with recurrence, eight women had a previous non-conservative treatment, six women had a non-conservative treatment after previous conservative treatment and the last five women underwent a second conservative treatment. One hundred and ninety-two of 209 women were alive without disease, five were alive with disease, eight died of intercurrent disease and four were lost to follow-up.
The recurrence rate was higher after conservative treatment than after non-conservative treatment (P <0.001) (Figure 1). No difference in the time to recurrence was found among the three groups.
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Discussion |
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Preoperative assessment of borderline ovarian tumors is mainly based on sonography and serum markers. In our study, large tumor size appeared to be a limitation for laparoscopy and an indication for first laparotomy. The sonographic aspect had less influence, as most of the borderline ovarian tumors exhibited features of benign tumors, with infrequent multilocular cysts and endophytic growth. Likewise, Rieber et al. [19] recently reported that transvaginal sonography, magnetic resonance imaging and positron emission tomography gave false-negative findings for borderline tumors. Moreover, using strict sonographic criteria of malignancy, Childers et al. [20
] showed that only 14% of tumors with sonographic signs of malignancy were effectively malignant.
In our study of women with borderline ovarian tumors, elevated CA125 serum levels were found in 41.6% of cases. Although mean CA125 serum levels were not significantly different between the laparoscopy and laparotomy groups, laparotomy was mainly performed in women with CA125 serum levels >35 U/ml. Malkasian [21] found that the sensitivity and specificity of elevated CA125 serum concentrations are higher in postmenopausal women. In our study, CA199 was less frequently assayed (26.3% of women), and was elevated in only 23.6% of cases. The number of women who had CEA assays was too small to determine its value in borderline ovarian tumors.
Perioperative examinations did not always distinguish among benign, borderline and malignant ovarian tumors [2224
]. Laparoscopy has become the routine approach to the treatment of benign ovarian tumors in France; indeed, this was the leading indication for gynecologic laparoscopic surgery in a French multicenter study [9
]. As borderline ovarian tumors tend to arise in younger women, in whom malignancy is less likely, initial surgery often uses laparoscopy. In our series 41.6% of women with borderline tumors initially underwent laparoscopy.
This is the largest reported series of laparoscopic management of borderline ovarian tumors. Although we demonstrated the feasibility of laparoscopic treatment for borderline ovarian tumors, certain limitations and risks must be discussed. Laparoconversion was necessary during 42 of the 149 initial laparoscopies. Signs of malignancy were the main indication for laparoconversion based on macroscopic aspect of adnexa or features suggesting an intra-abdominal dissemination. In contrast, although intra-operative histological examination allowed correct diagnosis of borderline ovarian tumors in 30 women managed by laparoscopy, only two laparoconversions were performed on the basis of this criterion, suggesting that this approach was considered adequate. Large tumor size was the second reason for laparoconversion. Few reports focused on laparoscopy for borderline ovarian tumors but no clear recommendations or limitations for laparoscopy were established [1316
].
Primary surgery for borderline ovarian tumors generally follows the guidelines on invasive ovarian cancer, requiring laparotomy. Peritoneal washing, random or oriented multiple biopsies, infra-colonic omentectomy and tumor debulking are recommended, together with appendectomy for women with mucinous borderline tumors [3, 17
, 25
]. However, only two-thirds of women in our study underwent peritoneal washing for cytological examination, regardless of the surgical approach. Moreover, initial staging was complete in only five (4.6%) laparoscopic procedures. However, it is important to underline that staging was complete in only 21.4% and 25.4% of cases after laparoconversion and laparotomy, respectively. These rates are in keeping with those reported by Lin et al. [26
] in a series of 250 women with borderline ovarian tumors treated by laparotomy. One potential explanation for inadequate initial staging, suggested by McGowan et al. [27
] for ovarian cancer, is that some obstetric gynecologists may not feel comfortable with technical aspects of surgical staging. Therefore, suspicious adnexal masses have to be treated in specialized units with available intra-operative histology, and by surgeons with high experience in laparoscopy. Indeed, in our study, two laparoconversions were performed because of difficulties with laparoscopic omentectomy. Another potential explanation is that ovarian borderline tumors behave in a benign fashion and that comprehensive laparotomic staging remains controversial, owing to its low impact on clinical management and outcome [26
]. However, in multivariate analysis, Trope et al. [17
] found that the main independent prognostic factor for disease-free and long-term survival was the FIGO stage. In our study, 30 women treated by laparoscopy underwent surgical restaging, and six (20%) were upstaged. This rate of upstaging is in keeping with those previously reported after laparotomy and laparoscopy (7% to 47%) [16
, 28
32
]. There is no consensus on which patients require restaging. Trimble and Trimble [1
] recommended a case-by-case approach, taking into account the adequacy of initial surgery, the tumor subtype and a potential recommendation for adjuvant therapy. In the present study, restaging operations were mainly proposed to young women and to women having undergone conservative treatment. Restaging was based on laparoscopy in 21 of 30 cases. Our results confirm those of Querleu et al. [16
], showing the feasibility of laparoscopic restaging in women with borderline tumors.
Other potential risks associated with laparoscopic management of borderline ovarian tumors include tumor cell dissemination and parietal metastasis [11, 33
]. In the present study, cyst rupture was more frequent during laparoscopic management, suggesting that laparoscopy may increase the risk of dissemination. However, ovarian cyst rupture was not related to the surgical route but to the frequency of cystectomy. No wound metastasis occurred in our series [33
]. The absence of this complication raises several issues regarding the risks of peroperative rupture and unprotected extraction of borderline ovarian tumors (35.9% and 52.4% of cases, respectively). The absence of wound metastasis could be related to the relatively short follow-up, the large proportion of women with early-stage disease, the absence of macroscopic intra-abdominal dissemination or ascites, and the biological characteristics of borderline ovarian tumors. Indeed, van Dam et al. [34
] reported that the port-site metastasis in women with ovarian cancer was linked to advanced stages, ascites, unprotected extraction, absence of peritoneal closure and the delay before beginning adjuvant chemotherapy. No data on incision closure were available in our study. In accordance with previous studies [35
, 36
], we confirm the feasibility of conservative treatment but with a significantly higher risk of recurrence (related to cystectomy and not to the surgical route). Therefore, cystectomy has to be restricted to women with one ovary or with bilateral lesions.
In conclusion, laparoscopy can be an alternative to laparotomy for the treatment of borderline ovarian tumors. However, this approach requires strict surgical procedure to avoid understaging, dissemination and wound metastasis. Prospective randomized trials are now needed to clarify the role of laparoscopy in women with borderline ovarian tumors.
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Acknowledgements |
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Received for publication May 26, 2004. Revision received October 22, 2004. Accepted for publication October 25, 2004.
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References |
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