ORIGINAL ARTICLE Year : 2022  |  Volume : 11  |  Issue : 4  |  Page : 215-220

Feasibility and safety of laparoscopic surgery in large ovarian masses

Tugba Kinay1, Yasemin Kizilkaya1, Sadiman Kiykac Altinbas2, Omer Lutfi Tapisiz2, Yaprak Engin Ustun1
1 Department of Obstetrics and Gynecology, Etlik Zubeyde Hanim Women's Health Training and Research Hospital, University of Health Sciences, Ankara, Turkey
2 Department of Obstetrics and Gynecology, Guven Hospital, Ankara, Turkey

Date of Submission02-Nov-2021Date of Decision31-Mar-2022Date of Acceptance20-Jul-2022Date of Web Publication07-Oct-2022

Correspondence Address:
Dr. Tugba Kinay
Department of Obstetrics and Gynecology, Etlik Zubeyde Hanim Women's Health Training and Research Hospital, University of Health Sciences, Yeni Etlik CD, No: 55, 06010 Kecioren, Ankara
Turkey

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/gmit.gmit_122_21

Objectives: To evaluate the feasibility and safety of laparoscopic surgery for large ovarian masses with benign features.
Materials and Methods: Women who underwent laparoscopic surgery for an ovarian mass with benign features between 2017 and 2019 at a tertiary referral center were included in the retrospective study. Based on the size of the ovarian mass, the women were divided into the case and control groups of ≥10 cm and <10 cm, respectively. Clinical characteristics, operative findings, histopathological results, and complication rates of the groups were compared.
Results: A total of 260 women, 64 women with large masses and 196 with small masses were included in the study. The operation time, intraoperative cyst rupture rate, complication rate, and hospital stay were similar in the case and control groups (P > 0.05). The cyst aspiration rate (29.7% vs. 5.1%, P < 0.001) and the unexpected malignancy rate (7.8% vs. 0.0% P = 0.001) were significantly higher in the case group than in the control group.
Conclusion: Laparoscopic surgery was found feasible for the treatment of women with large ovarian masses. However, a higher unexpected malignancy rate requires the careful patient selection and appropriate counseling preoperatively in these cases.

Keywords: Feasibility, laparoscopic surgery, minimally invasive surgery, ovarian cancer, ovarian mass

How to cite this article:
Kinay T, Kizilkaya Y, Altinbas SK, Tapisiz OL, Ustun YE. Feasibility and safety of laparoscopic surgery in large ovarian masses. Gynecol Minim Invasive Ther 2022;11:215-20
How to cite this URL:
Kinay T, Kizilkaya Y, Altinbas SK, Tapisiz OL, Ustun YE. Feasibility and safety of laparoscopic surgery in large ovarian masses. Gynecol Minim Invasive Ther [serial online] 2022 [cited 2022 Nov 8];11:215-20. Available from: https://www.e-gmit.com/text.asp?2022/11/4/215/358042   Introduction 

Ovarian masses are common conditions requiring surgery encountered by gynecologists. Approximately 5%–10% of women require surgical treatment for suspected ovarian neoplasm during their lifetimes.[1] The advantages of laparoscopic surgery have made the laparoscopic approach a primary choice in the surgical treatment of benign small ovarian masses.[2],[3] Reduced perioperative morbidity, improved cosmesis, decreased length of hospital stay, and less adhesion formation and postoperative pain in laparoscopic surgery improve the quality of postoperative life.[4] However, concerns remain about the feasibility and safety of laparoscopic surgery for large ovarian masses. Some surgeons still refrain from laparoscopic surgery for large masses because of difficult visualization, the risk of damage to intra-abdominal organs, the risk of an unintended rupture of occult malignancy, and the risk of intraperitoneal spillage, and the need for subsequent adjuvant therapy. The study aimed to assess the feasibility and safety of laparoscopic treatment for large ovarian masses that were preoperatively presumed benign.

  Materials and Methods 

This retrospective study was conducted at the gynecology department of a tertiary care center between January 2017 and December 2019. The study protocol was approved by the institutional review board (2020/01-28) and complied with the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent for future use of medical records in scientific researches was obtained from all women at the time of hospital admission.

Medical records of women who underwent surgery for an adnexal mass were reviewed. Women who had an ovarian mass with a low risk of malignancy (risk of malignancy index [RMI] <200 or increased serum cancer antigen 125 [CA125] level with typical characteristics of endometrioma and mature cystic teratoma by ultrasonographic examination) and underwent laparoscopic surgery were included in the study. Women who had an extraovarian adnexal mass, underwent laparotomy for the initial surgical approach, and had high-risk malignancy findings (tumors with thick irregular septa, with complex consistency, omental cake, RMI >200 in the absence of typical ultrasonographic characteristics of endometrioma or mature cystic teratoma) were excluded from the study.

As a part of the routine gynecological examination, ultrasonography was performed preoperatively by experienced gynecologists using a 6–10 MHz transvaginal probe (Logiq P5, GE Healthcare Inc., Milwaukee, Wisconsin, USA) with an empty bladder in the lithotomy position. The RMI was calculated using the CA 125 value, postmenopausal status (M), and ultrasonography score (U) (RMI = U × M × CA125), as previously reported.[5] In this scoring method, an ultrasound score was assigned according to the following ultrasound features that suggest malignancy: multilocular cystic mass, solid areas, bilaterality, ascites, and extraovarian tumor. Postmenopausal status was defined as being more than 40 years old with at least 1 year of amenorrhea. CA125 levels were measured by using the Elecsys CA 125 II kit (Roche, Mannheim, Germany).

Demographic, clinical characteristics, ultrasonography, laboratory, operation, and histopathological reports of all participants were reviewed. Women were divided into two groups based on the diameter of the ovarian mass. A large ovarian mass was defined as ≥10 cm in diameter on preoperative ultrasonographic findings. Women with large masses were included in the case group. The control group consisted of women with ovarian masses <10 cm in diameter. Age, parity, body mass index, menopausal status, history of abdominal surgery, tumor diameter, ultrasonographic findings, CA 125 serum level, surgical procedures, operating time, preoperative and postoperative day one hemoglobin concentration, intra and postoperative complications, conversion to laparotomy, length of hospital stay, and histopathological results of groups were compared.

All surgical procedures were carried out by the experienced gynecological surgical team in a single referral center. Preoperatively, written informed consent was obtained from all participants regarding the use of their medical records for scientific research, frozen section analysis, the risk of complications and unexpected malignancy, and the need for possible conversion to laparotomy or other indicated procedures. Laparoscopy was performed in the lithotomy position under general anesthesia. Pneumoperitoneum was established with a Veress needle or via an open-access technique at pressure settings of 15 mmHg. The initial trocar was inserted umbilically or at the Palmer point (left subcostal mid-clavicular region) in women with suspected intra-abdominal adhesion. Then, accessory trocars were placed in the abdominal cavity in the right and left quadrants. A thorough inspection of the abdominal cavity and adnexal mass was carried out next. A uterine manipulator was used in women with severe pelvic adhesions. Cystectomy or salpingo-oophorectomy was performed depending on the women's age and suspicious appearance of the ovarian mass based on visual inspection. In women with an ovarian cyst exceeding the capacity of the endobag or wholly occupying the abdominal cavity, the cyst content was aspirated by a suction tube. During the aspiration process, intraperitoneal spillage of the cystic contents was carefully avoided. Intraperitoneal spillage was also avoided by sealing the puncture site after aspiration of the cyst content using an electrothermal bipolar vessel sealer (LigaSure  Atlas More Details™, Valleylab, Boulder, CO, USA). After the cystectomy or salpingo-oophorectomy, the ovarian masses were placed into a synthetic endobag and removed from the abdominal cavity to prevent spillage into the abdominal cavity. The operating time was defined as the time from the anesthesia induction to the closure of all port sites.

All ovarian masses were sent for frozen pathological examination at the time of the operation. When a malignant or borderline tumor was detected, cases were consulted intraoperatively in the gynecologic oncology unit. Explorative laparotomy with tumor staging was carried out by a gynecologic oncology team if indicated. Further confirmatory paraffin pathological examination was carried out in all histopathological specimens. Borderline tumors were classified as malignant for statistical analysis.

Data were statistically analyzed using SPSS v. 17.0 for Windows (SPSS, Inc., Chicago, IL, USA). The Shapiro–Wilk test was used to test normality for continuous variables. Descriptive statistics are presented as mean ± standard deviation or median (range), based on the assumption of a normal distribution. The Student's t-test was used for normally distributed continuous data, whereas the Mann–Whitney U-test was used for data not normally distributed. Pearson's Chi-squared test or Fisher's exact test was used to compare categorical variables. The level of statistical significance was set at P < 0.05.

  Results 

During the study period, a total of 260 women, 64 women with a large mass and 196 without, underwent laparoscopic surgery for an ovarian tumor. As shown in [Table 1], the demographic and clinical characteristics of the women with and without large ovarian masses were similar. The serum levels of CA 125 and RMIs were also similar between the two groups (P > 0.05). Through ultrasonographic imaging, the median diameter of the ovarian mass was determined to be 11.2 cm (10–22.5 cm) in women with a large mass and 6.8 cm (2.5–9.8 cm) in women without a large mass. Multilocular cystic appearance (45.3% vs. 24.5%, P = 0.002) and intra-abdominal ascites (7.8% vs. 1.5%, P = 0.024) were more common in women with large ovarian masses. However, the bilaterality rate was lower in this group. While 4 (6.3%) women had bilateral ovarian masses in the large group, 37 (18.4%) women had them in the control group (P = 0.016).

Table 1: Demographic and clinical characteristics of women with and without large ovarian tumor

Click here to view

Operative details and histopathological results of women with and without large masses are shown in [Table 2]. Emergent surgery was performed in nine (14.1%) of the women with large ovarian masses due to torsion and 19 (9.7%) of the women without (17 due to torsion and two due to cyst rupture). The salpingo-oophorectomy rate was significantly higher in women with large masses than without (65.6% vs. 44.4%, P = 0.003). There was no significant difference in terms of laparoscopy technique, operation time, complication rate, preoperative and postoperative Hb levels, and length of hospital stay between the two groups (P > 0.05). While the intraoperative cyst rupture rate of the two groups was similar (26.6% vs. 35.7%, P = 0.178), aspiration of the cyst content was performed more commonly in women with large ovarian cysts (29.7% vs. 5.1%, P < 0.001). The conversion to laparotomy rate was higher in women with large ovarian masses than without (7.8% vs. 0.0% P = 0.001). All the laparotomies were performed in cases with unexpected malignancy. In the large-mass group, one woman (1.6%) who underwent cystectomy had intraoperative bleeding requiring transfusion. The histopathological diagnosis of the cystectomy specimen indicated a mature cystic teratoma. No other intraoperative or postoperative complications occurred in either group.

Table 2: Operative details and histopathological results of women with and without large ovarian tumor

Click here to view

The histopathological results of women with and without large ovarian masses were different. In benign pathologies, while follicular cysts were the most common pathology in the small-mass group (22.4% vs. 10.9%, P = 0.044), the most common pathology in the large-mass group was mucinous cystadenomas (25.0% vs. 9.2%, P = 0.001). The unexpected malignancy rate was also significantly higher in the large ovarian mass group. While 5 (7.8%) women had malign or borderline tumors in the large-mass group, no women with ovarian masses smaller than 10 cm in diameter had either malign or borderline tumors (P = 0.001). The median RMI was 13.5 (12–540) in women with malignant tumors. The details of malignant cases (four borderline and one malignant ovarian tumor) are shown in [Table 3].

  Discussion 

The study results showed that laparoscopic surgery of large ovarian masses was feasible. The operation time, complication rate, and length of hospital stay were similar in the large and small ovarian mass groups. However, unexpected malignancy risk was higher in women with large masses than without. While there were no malignant cases in women with ovarian masses presumed benign and <10 cm in diameter, five unexpected malignancies were detected in the large-mass group.

Difficulty in the surgical technique is one of the reasons for hesitating in laparoscopic surgery for large ovarian tumors. Secure port insertion, providing safe surgical vision and manipulation of surgical equipment may become more difficult in women with large ovarian masses. However, like previous reports, the presented findings showed that laparoscopic surgery was feasible in large adnexal tumors presumed benign. Intraoperative and postoperative complication rates were low in the large-mass group, as previously reported.[6],[7] Intraoperative bleeding requiring blood transfusion in a woman with a large ovarian mass was the only complication reported in the study population. The operation time and the length of hospital stay were comparable with those of the control group. On the other hand, in our study, the cyst rupture rate (26.6%) was lower than previously reported. Casarin et al.[7] and Ghezzi et al.[8] reported an intraoperative spillage rate of more than 50% in women undergoing laparoscopic surgery for an adnexal mass with a size of 10 cm or larger. The reason for these discordant rates may be the controlled cyst aspiration application in our study. The cyst content was aspirated in 29.7% of women with large ovarian masses.

Conversion to laparotomy may be required in some cases during laparoscopic surgery because of intra-abdominal adhesions, difficulties in surgical technique, or malignancy. In a multicenter study, conversion to laparotomy was reported in 12 of 186 (6.5%) women who underwent laparoscopic surgery for an adnexal mass 10 cm in diameter or larger.[8] The reasons for conversion to laparotomy were technical difficulties in seven women and malignancies in five women. In our study, the rate of conversion to laparotomy was slightly higher than in the previous report. Conversion to laparotomy in five women (7.8%) occurred because the frozen section analysis intraoperatively confirmed the pathology as malignant. There was no conversion to laparotomy for technical difficulties or other reasons. In the large-mass group, the unexpected malignancy rate of 7.8% was relatively higher than previously reported. A 5.6% malignancy rate was reported in a review published in 2016.[9] Differences in the patient selection criteria of the studies may be the reason for the higher malignancy rate in our study.

Intraoperative rupture and spillage risk of an unexpected malignant tumor is the primary concern in laparoscopic surgery of large ovarian masses. Intraoperative rupture of ovarian masses could lead to upstaging of an occult malignancy.[10] Therefore, distinguishing malignant ovarian masses from benign ovarian masses is essential for gynecologists interested in minimally invasive surgery. Various tumor markers and preoperative scoring systems have been used for this purpose.[5],[11] The RMI is one of the preoperative scoring systems have been used.[5] Moore et al.[12] reported that the RMI had a sensitivity of 84.6% and a specificity of 75% for distinguishing benign ovarian masses from epithelial ovarian cancer. The RMI includes ultrasonographic features of an ovarian mass, menopausal status, and serum level of CA125 but not the mass size. It is known that the risk of malignancy is higher in large ovarian masses,[13] and it is not yet clear whether the predictive value of the RMI for malignancy in large and small ovarian masses is similar. In our study, no malignancy was observed in women with ovarian masses smaller than 10 cm in diameter and RMI <200. However, there were four malignant cases (three borderline tumors and one malignant tumor) with RMI <200 in the large ovarian mass group. Based on these findings, clinicians should avoid intraperitoneal spillage during laparoscopic surgery of large ovarian masses, even if it is preoperatively presumed benign. Purse-string sutures or surgical clips were previously used after cyst content aspiration to prevent intraperitoneal spillage.[6] We used a different technique for this purpose. We sealed the puncture site using an electrothermal bipolar vessel sealer in cases that underwent cyst aspiration.

In our study, intraoperative rupture rates of small and large ovarian masses were not significantly different. Intra-abdominal rupture of the tumor capsule upstages ovarian cancer from IA to IC1 on the International Federation of Gynecology and Obstetrics scale.[14] There is disagreement about the impact of intraoperative ruptures on the prognosis of ovarian malignancy.[15] Whereas some authors reported that an intraoperative capsule rupture worsens the prognosis,[16],[17] others did not.[18],[19] Vergote et al.[16] and Bakkum-Gamez et al.[17] reported that intraoperative capsule rupture was associated with lower disease-free survival in stage I epithelial ovarian cancer. However, according to Seidman et al.[18] and Ahmed et al.,[19] tumor rupture was not an adverse prognostic factor in these patients. More prospective randomized trials are needed to make a definitive decision on this issue.

The cyst aspiration rate of the large-mass group was higher than that of the small-mass group in the study population. Several techniques have been previously described to aspirate and avoid intraperitoneal spillage of large ovarian mass contents during minimally invasive surgery.[20],[21],[22],[23],[24] Hicks-Courant et al.[20] applied a skin adhesive to the tumor and a surgical glove to the glue area after exposing the tumor wall via mini-laparotomy, then aspirated the cyst content within the glove. Song and Sung[21] covered the large cyst surface with a sterilized vinyl membrane applied with a skin adhesive, then punctured and aspirated cyst contents during laparoscopic surgery. Chong et al.[22] discussed the purse-string suture technique before cyst aspiration during single-port assisted extracorporeal ovarian cystectomy. They reported that the macroscopic intraperitoneal spillage rate was significantly lower than with the conventional technique. However, microscopic spillage with these techniques was not reported. There is no evidence yet on whether controlled aspiration causes microscopic intraperitoneal spillage and upstaging of malignant cases. Further studies evaluating the impact of intraoperative aspiration of ovarian carcinoma on the prognosis are needed.

The large cohort and presence of a control group are the strengths of this study. Previous reports about the efficacy of laparoscopic surgery in large ovarian masses are case studies[25],[26],[27],[28] or cohort studies,[6],[7],[8],[29],[30] including only patients with large masses and without a control group. However, the limitations of this study include the retrospective design and insufficient data, such as quantitative blood loss and long-term outcomes of malignant cases. Furthermore, preoperative ultrasonographic examinations and malignancy risk assessments were not carried out by a single clinician. This could cause patient selection bias.

  Conclusion 

Laparoscopic surgery is feasible in women with large ovarian masses. The operation time, hospital stay, and complication rate in women who underwent laparoscopic surgeries for large masses were comparable to those in women with small masses. However, an increased risk of unexpected malignancy and intraoperative spillage of malignant tumors should be considered in these women. Proper patient selection and appropriate counseling are obligatory before laparoscopic surgery for large ovarian masses.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

  References 
1.NIH consensus conference. Ovarian cancer. Screening, treatment, and follow-up. NIH consensus development panel on ovarian cancer. JAMA 1995;273:491-7.  
    2.Parker WH, Berek JS. Management of selected cystic adnexal masses in postmenopausal women by operative laparoscopy: A pilot study. Am J Obstet Gynecol 1990;163:1574-7.  
    3.Yuen PM, Yu KM, Yip SK, Lau WC, Rogers MS, Chang A. A randomized prospective study of laparoscopy and laparotomy in the management of benign ovarian masses. Am J Obstet Gynecol 1997;177:109-14.  
    4.Sisodia RM, Del Carmen MG, Boruta DM. Role of minimally invasive surgery in the management of adnexal masses. Clin Obstet Gynecol 2015;58:66-75.  
    5.Jacobs I, Oram D, Fairbanks J, Turner J, Frost C, Grudzinskas JG. A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Br J Obstet Gynaecol 1990;97:922-9.  
    6.Cho BR, Han JW, Kim TH, Han AR, Hur SE, Lee SK, et al. Single port access laparoscopic surgery for large adnexal tumors: Initial 51 cases of a single institute. Obstet Gynecol Sci 2017;60:32-8.  
    7.Casarin J, Laganà AS, Uccella S, Cromi A, Pinelli C, Gisone B, et al. Surgical treatment of large adnexal masses: A retrospective analysis of 330 consecutive cases. Minim Invasive Ther Allied Technol 2020;29:366-74.  
    8.Ghezzi F, Cromi A, Bergamini V, Uccella S, Siesto G, Franchi M, et al. Should adnexal mass size influence surgical approach? A series of 186 laparoscopically managed large adnexal masses. BJOG 2008;115:1020-7.  
    9.Eltabbakh G. Laparoscopic surgery for large ovarian cysts-review. Trends Gynecol Oncol 2016;1:109.  
    10.Sainz de la Cuesta R, Goff BA, Fuller AF Jr., Nikrui N, Eichhorn JH, Rice LW. Prognostic importance of intraoperative rupture of malignant ovarian epithelial neoplasms. Obstet Gynecol 1994;84:1-7.  
    11.Dolgun ZN, Kabaca C, Karateke A, İyibozkurt C, İnan C, Altıntaş AS, et al. The use of human epididymis 4 and cancer antigen 125 tumor markers in the benign or malignant differential diagnosis of pelvic or adnexal masses. Balkan Med J 2017;34:156-62.  
    12.Moore RG, Jabre-Raughley M, Brown AK, Robison KM, Miller MC, Allard WJ, et al. Comparison of a novel multiple marker assay versus the risk of malignancy index for the prediction of epithelial ovarian cancer in patients with a pelvic mass. Am J Obstet Gynecol 2010;203:e1-6.  
    13.American College of Obstetricians and Gynecologists' Committee on Practice Bulletins-Gynecology. Practice bulletin No. 174: Evaluation and management of adnexal masses. Obstet Gynecol 2016;128:e210-26.  
    14.Prat J, FIGO Committee on Gynecologic Oncology. Staging classification for cancer of the ovary, fallopian tube, and peritoneum. Int J Gynaecol Obstet 2014;124:1-5.  
    15.Tantitamit T, Lee CL. Is it the time for laparoscopic management of early-stage ovarian malignancies? Gynecol Minim Invasive Ther 2018;7:93-103.  
[PUBMED]  [Full text]  16.Vergote I, De Brabanter J, Fyles A, Bertelsen K, Einhorn N, Sevelda P, et al. Prognostic importance of degree of differentiation and cyst rupture in stage I invasive epithelial ovarian carcinoma. Lancet 2001;357:176-82.  
    17.Bakkum-Gamez JN, Richardson DL, Seamon LG, Aletti GD, Powless CA, Keeney GL, et al. Influence of intraoperative capsule rupture on outcomes in stage I epithelial ovarian cancer. Obstet Gynecol 2009;113:11-7.  
    18.Seidman JD, Yemelyanova AV, Khedmati F, Bidus MA, Dainty L, Boice CR, et al. Prognostic factors for stage I ovarian carcinoma. Int J Gynecol Pathol 2010;29:1-7.  
    19.Ahmed FY, Wiltshaw E, A'Hern RP, Nicol B, Shepherd J, Blake P, et al. Natural history and prognosis of untreated stage I epithelial ovarian carcinoma. J Clin Oncol 1996;14:2968-75.  
    20.Hicks-Courant K, Awtrey CS, Kim YB. Controlled decompression of large ovarian cystic tumors via mini-laparotomy using Dermabond Advanced™. Gynecol Oncol Rep 2020;32:100536.  
    21.Song T, Sung JH. Leak-proof technique in laparoscopic surgery for large ovarian cysts. J Obstet Gynaecol 2021;41:106-11.  
    22.Chong GO, Hong DG, Lee YS. Single-port (OctoPort) assisted extracorporeal ovarian cystectomy for the treatment of large ovarian cysts: Compare to conventional laparoscopy and laparotomy. J Minim Invasive Gynecol 2015;22:45-9.  
    23.Pecorelli S, Tonegatti UG, Stern MV, Bulotta AL, Laffranchi F, Stegher C, et al. Management of large pediatric and adolescent ovarian neoplasms with a leak-proof extracorporeal drainage technique: Our experience using a hybrid minimally invasive approach. J Pediatr Adolesc Gynecol 2021;34:394-9.  
    24.Watson L, Gavens E, Pachl M, Singh M, Soccorso G, McCarthy L, et al. Controlled aspiration of large paediatric ovarian cystic tumours. J Pediatr Surg 2022;57:711-4.  
    25.Salem HA. Laparoscopic excision of large ovarian cysts. J Obstet Gynaecol Res 2002;28:290-4.  
    26.Sagiv R, Golan A, Glezerman M. Laparoscopic management of extremely large ovarian cysts. Obstet Gynecol 2005;105:1319-22.  
    27.Rhode JM, Advincula AP, Reynolds RK, Burke WM. A minimally invasive technique for management of the large adnexal mass. J Minim Invasive Gynecol 2006;13:476-9.  
    28.Zahid AZ, Rahman NA, Karim ZR, Omar E. Laparoscopic management of a large extragonadal teratoma. Gynecol Minim Invasive Ther 2022;11:51-3.  
  [Full text]  29.Göçmen A, Atak T, Uçar M, Sanlikal F. Laparoscopy-assisted cystectomy for large adnexal cysts. Arch Gynecol Obstet 2009;279:17-22.  
    30.Hong JH, Choi JS, Lee JH, Son CE, Jeon SW, Bae JW. Laparoscopic management of large ovarian tumors: Clinical tips for overcoming common concerns. J Obstet Gynaecol Res 2012;38:9-15.  
    

 
 

  [Table 1], [Table 2], [Table 3], [Table 1], [Table 2], [Table 3]