Menopause: The Journal of The North American Menopause Society Voi, 16, No. 5, pp. 966-970 DOI: I0.i097/gme.0b013e3181a037ed © 2009 by The North American Menopause Society
Initial laparoscopie access in postmenopausal women: a preliminary prospective study Andrea Tinelli, Affi)/ Antonio Malvasi, MD,2 Marcella Guido, PhD,3 Olav Istre, MD, PhD,4 Joerg Keckstein, MD, PhD,5 and Liselotte Mettler, MD, PhD6 Abstract Objectìve: Estrogen loss at menopause has a profound influence on skin, with postmenopausal atrophy and loss of tone and elasticity. Because more than 50% of major laparoscopie complications occur during initial entry under thè abdominal skin, thè efficacy and thè safety of two laparoscopie access techniques were compared in postmenopausal women. Methods: One hundred eighty-six postmenopausal women underwent laparoscopie surgery for simple ovarian cysts: 89 were assigned to direct optìcal access (DOA), abdominal entry (group I), and 97 to thè classic closed Veress needle approach, pneumoperitoneum, and trocar entry (group II). The following parameters were compared: rime needed for entry into thè abdomen, occurrence of vascular and/or bowel injury, and blood loss. Results were analyzed using SAS software, considering P value less than 0.05 as significant. Results: No statistìcally significant difFerences were observed in thè occurrence of major vascular and/or bowel injury between thè two techniques (P > 0.05), whereas time for abdominal entry was significantly reduced in thè DOA group, as well as thè occurrence of minor vascular injuries (P < 0.05). Conctusions: Results of this preliminary comparison on tìie DOA and thè Veress methods, commonly used by gynecologists, suggest that thè visual entry System offers a statistical advantage over thè closed Veress needle approach, in terms of time saving and limiting minor vascular injuries, thus enabling a safe and fasi visually guided entry in postmenopausal women. Key Words: Menopause - Gynecological laparoscopy - Initial abdominal access - Skin aging - Direct optìcal access - Veress needle — Estrogen.
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hysiological changes occur with aging in ali organ systems of thè female body, particularly on thè skin. Estrogens affect several skin functions, such as hair growth, pigmentation, vascularity, elasticity, and waterholding capacity, thus influencing skin thickness, wrinkling, and moisture. The epidermis of thè skin atrophies with age and lean body mass declines, primarily due to loss and atrophy of muscle cells. The relevant hypoestrogenism accompanying menopause exacerbates thè deleterious effects of botii intrìnsic and
Received November 24, 2008; revised and accepted February 5, 2009. From thè 'Department of Obstetrics and Gynaecology, Vita Pazzi Hospital, Lecce; 2Depaitment of Obstetrics and Gjraeoofcgy, Santa Maria Hospital, Bari; 'Department of Biologica! and Enviiuomental Sciences and Technologies, Laboratoiy of Hygjene, Unirersity of Salente. Lecce, Italy; 4Depanment of Gynaecotogy and Obstetrics, Ulkvaal University Hospital, Kirkeveien, Oslo, Norway; ^Department of Obstetrics and Gynaecotogy, LandesKrankenHouse, Villach, Austria; and 'Department of Obstetrics and Gynaecology, Kiel School of Gynecological Endoscopy, University Hospitals Schleswig-Holstein, Campus Kiel, Germany. Financial disclosure/conflicts of interest: None reported. Address reprint requests to: Andrea Tinelli, MD, Department of Obstetrics and Gynecology, Vtto Pazzi Hospital, Piazza Muratore, 73100 Lecce, Italy. E-mail:
[email protected] 966
environmental aging, especially on thè cutis, where they have clearly played a key role in skin aging homeostasis, as observed in perimcnopausal years.' Among thè postmenopausal skin changes, hypoestrogenism promotes a collagen drop and a decrease in both elasrin content and skin thickness; collagen atrophy is, in fact, a major factor in skin aging, associated with a progressive increase in extensibility and a reduction in elasticity. This makes thè skin more fragile and susceptible to trauma, leading to more lacerations and bruising and wound healing impairment in older women.2 Changes in skin characteristìcs might, therefore, influence thè initial laparoscopie abdominal access in postmenopausal women. Given that laparoscopie surgery is more advantageous than laparotomy for both women and gynecologists beoau.se of thè significantly reduced ovcrall risk of complications,3 more tfian 50% of major laparoscopie complieations actually occur during initial entry into thè female abdomen at any age.3'4 In fact, major vascular injury during initial laparoscopie access is a major cause of death from laparoscopy, second only to anesthesia and bowel injury, with a reported mortality rate of 15%.5 Several techniques and technologies have been introduced to minimize entry-related complications, which include many types of entry, namely, thè Veress insufflation needle
Menopause, Voi 16, No. 5, 2009
Copyright © 2009 The North American Menopause Society. Unautnorized reproductiO'" of 'h'.s artide s prohiDMed.
1NJTIAL LAPAROSCOP1C ACCESS IN POSTMENOPAUSAL
approach, invented by Janos Veres in 1938 to create a pneumoperitoneum followed by trocar insertion; thè open laparoscopy (by Hasson method); thè direct trocar entry technique; thè visual entry method with thè Temamian trocarless cannula; or thè direct optical access (DOA) technique.3 The Veress needle approach, characterized by pneumoperitoneum creatìon followed by trocar insertion, is thè most common gynecological entry method. An appropriate pneumoperitoneum is achieved through a small intra-abdominal puncture before entering with a trocar. Although laparoscopie access has not shown a clear superiority in terms of safety compared with other approaches, most gynecologists worldwide use thè closed Veress laparoscopie entry or Hasson method.5"7 Accordingly and because of hypoestrogenic changes in postmenopausal female skin and thè musculature of thè abdominal wall, we evaluated thè possible differences in initial laparoscopie access among thè different techniques used in postmenopausal women. Research in scientific literature proves that no such findings have yet been reported. Therefore, we have made a preliminary comparison of both methods to evaluate thè efficacy and safety of a new procedure—direct optical trocars—versus a standard, widely used procedure, that is, thè closed Veress needle access, in postmenopausal women. METHODS From January 2004 to October 2008, a total of 186 postmenopausal women were scheduled to undergo laparoscopy for simple, persistent postmenopausal ovarian cysts in multiple European gynecological centers. These women were randomized in parallel assignment to gynecological laparoscopy for either optical-guided or Veress needle entry before surgery at a randomization ratio of 1:1. Before laparoscopy, ali participants underwent a gynecological and pelvic ultrasound evaluation to best assess possible ovarian cysts, a Pap smear, and, if necessary, a diagnostìc hysteroscopy to exchide any premalignant or malignant conditìons. Inclusion criteria included thè following: existence of a simple unilateral ovarian cyst with at least 4-cm diameter and a maximum of 8-cm diameter, with no evidence of echographic malignancy features (nonfatty solid or vascularized tissue, no thick septations, and no papillary projections), exhibitìng serum C Al 25 levels within normal limits, with a body mass index between 20 and 28 kg/m2, an uneventftil speculum examination, and no use of hormonal therapy (HT) for at least 1 year. Moreover, to establish thè menopause status, ali women were included only if they had been amenorrheic for at least 12 months. Participants with a history of open abdominal surgery or large ovarian cysts (9 cm in diameter or greater), or those who underwent previous periumbilical surgery were excluded from thè study because of possible interfering factors. Participants with echographic patterns of malignancy (includ-
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ing thick, irregular walls and septa, papillary projections, solid echogenic loculi, and vascularized tissue) were also excluded, being potentially cancer-prone. AH scheduled participants provided informed coment before surgery. They were subsequently randomized to two groups by clinicians. Group I, including 89 participants, was assigned to direct optical laparoscopie access, whereas surgery was performed on ali 97 participants assigned to group II by means of thè classical Veress needle method plus trocar entry. Single-use, identical cost trocars were chosen, and ali of thè surgical procedures were performed by residents who were experts in gynecological laparoscopy. Ali laparoscopie procedures were performed under generai anesthesia by endotracheal intubations, and ali women received a prophylactìc dose of 2 g cefazoline IV. The DOA technique was performed as follows: first, a 10-mm intraumbilical incision was made and thè abdominal wall was lifted; sccond, an optical bladcless trocar ("Endopath" Trocars; Ethicon, Johnson & Johnson, Somerville, NJ) with a laparoscope was introduced directly into thè abdominal cavity by applying a Constant axial penetrating force under direct visual identification of abdominal wall layers, startìng from subcutaneous fat tissue to thè rectus sheath and thè peritoneum; and, finally, thè intraabdominal contents were examined. This was followed by secondary creation of a pneumoperitoneum. The classic closed Veress needle method was used (Ethicon, Johnson & Johnson) followed by pneumoperitoneum, and a single-use conical blind blunt-tipped trocar insertion was performed as described in thè literature.3 Gynecologists guided thè Veress needle steadily in an even 45° angle position through thè umbilicus, performing a midsagittal intraumbilical incision, with thè scalpel angled at 30° to thè woman's abdominal wall. The Veress needle perforated thè abdominal wall layers to thè abdominal cavity, and surgeons made thè "injection-aspiration test" using a 20-mL NaCl syringe connected to thè needle to aspirate or, alternatively, by placing a drop of water on thè extra-abdominal end of thè needle to avoid puncturing of vessels or thè bowel and confimi thè negative intra-abdominal pressure. The Veress needle was connected to a CO2 flow tube, insufflating 2 to 2.5 L of CO2 into thè abdominal cavity, until a tympanic sound was heard and symmetric distension of ali four abdominal quadrants was obtained. The insertion needle was then carefully withdrawn, and thè abdominal wall was grasped by thè surgcon below thè umbilicus at both sides, with thè help of an assistant, and lifted to insert thè single-use conicai blind blunt-tìpped trocar (Ethicon, Johnson & Johnson). The umbilical trocar insertion was performed by thè surgeon using thè right hand, with thè index finger along thè barrel of thè trocar, accurately pressing it to enable correct positioning of thè instrument at no more than 2 cm behind thè umbilicus. Subsequently, a warmed laparoscope was inserted; thè middle and lower abdomen was visualized to exclude injury of anatomie structures, such as thè bowel and big or small vessels of thè omentum or jejunal mesentery. Menopause, Voi 16, No. 5, 2009
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This investigatici! focused only on laparoscopie access parameters, without analyzing other surgical findings or evaluating mean operating lime to complete ali cases or complications during surgery. The laparoscopie entry techniques were analyzed by means of thè following parameters: lime from incision of thè subumbilical skin to visualizatìon of thè intra-abdominal contents via thè laparoscope, thè occurrence of major and minor vascular and bowel injuries (as described in "Results"), blood loss during laparoscopie access (estimated by two independent reviewers), and weight of swabs in milliliters. The data collected were analyzed using STATVIEW 5.1 for Macintosh (Abacus Concepts, Inc., Berkeley, CA, 1992). Continuous variables were expressed as mean ± SD, whereas categorìcal variables were expressed in absolute terms. Fisher's exact test was used to analyze categorìcal variables, whereas comparisons between thè two groups with normality and homogeneity of variances were performed by means of thè two-tailed unpaired Student's t test. Altematìvely, comparisons between groups with abnormality and heterogeneity of variances were performed by means of thè Welch t test, Values of 0.05 were considered statistically significant. RESULTS Participants were ali white, and thè characteristics of thè two groups, shown in Table 1, were homogeneous and equally distributed, with no statistical differences, except for a significant difference (P < 0.0001) in tìme from menopause in favor of thè first group, subjected to DOA. Time from menopause was more than 1 year in both groups. There were no significant differences between thè two groups in blood loss (P - 0.1202) and in thè occurrence afiminrarwaBnilan-iniuriBas ((P'=Qjfi223^j, whidD, imtheVfflBaas group, compriseli two acci'dentàl neeiile punctures óT a jejunal srnall vessel and of one omental vessel, respectively, both of which spontaneously resolved within thè first minutes of thè operation. In thè DOA group, one minor vascular injury involving rupture of an omental vessel was reported. "Bleedìng resolved spontaneously within 1 minute after thè injury. The time needed to establish adequate abdominal access was significantly reduced hi thè DOA access group (P < 0.0001). Ali data are shown in Table 2. TABLE I. Baseline homogeneous characteristics ofthe stucty participants Direct optìcal access group (n = 89)
Veress needle access group (n = 97)
Age,y
52.9 ±2.1
53.4 ±1S
BMI, kg/mz Parity Time from menopause,
25.3 ± 0.8 2.3 ± 0.8 17 ± 1.4
26.1 ± 0.9
0.0002 (/» < 0.001)*
2.2 ± 0.8 19 ± 0.9
0.5033 (NSf 0.0001*
Characteristic
0.191 I
Dates are expressed as mean ± SD. BMI, body mass index. "Statistical analysis was performed by an unpaired Student's t test. ''Statistica! analysis was performed by unpaired / test with Welch correctìon: a > 0.05, df= 1.45, P < 0.0001.
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TABLE 2. Intraoperative difference and complications among thè two laparoscopie access groups
Variatale
Direct optical Veress needle access group access group (n •= 89) (n = 97)
Duratìcm of entry 65.7+ 11.9 192.8 ± 5.6 (mean ± SD), s 8.4 ± 7.2 Blood loss (mean ± SD), mL 9.3 ± 5.5 0 0 Major vascular injuries 1 Minor vascular injuries 3 0 0 Minor bowel injuries For statistical analysis, we used thè following: "Unpaired t test with Welch correction. *Unpaired Student's t test. "Tisher's exact test.
P
0.0001" 0.1202 (NS)* 0.6223 (NSf
Ali operations were terminated without any further intraoperatìve or postoperatìve complications. Because DOA is a new method of access in thè abdomen, to observe accurately any possible complications in thè eariy postoperatìve period, ali women were discharged on thè following day. Postoperative follow-up at 4 to 6 weeks did not show any late complications in wound healing. DISCUSSION Menopause is associated with changes in body composition: a decrease in collagen synthesis, a loss of lean body mass, and an increase in total and abdominal fat mass.8 Estrogen deficiency seems to play a key role in menopause-related changes in skin compositìon and exerts a considerable influence on it.9 Thus, thè skin is one of thè largest organs of thè body significantly affected by thè aging process and by menopause.8'9 This is shown by thè estrogen level drop in skin odlulàn aomnHnraitS§, inmiiatmjg aa rmtiialium off aallkgain content after menopause. Consequently, postmenopausal changes include a thickening in thè papillary dermis of thè elastic fibers, which also seem to be better oriented and slightly more numerous.10 Accordingly, thè dermal cellular metabolism is also influenced by thè hypoestrogenic state of menopause, leading to changes in thè collagen content and alteratìons in thè concentration of glycoaminoglycans and, most importantly, in thè water contentu Moreover, thè turnover rate of cells in thè stratum corneum decreases with menopause. Thus, in women older than 65 years, it takes 50% longer to reepithelize blistered skin than in young adults.' A linear decrease in skin collagen content of approximately 10% per year in adult life years was reported, with thè skin collagen content being lower in women than in men.2 In menopause, skin collagen content decreases, and thè subsequent loss of collagen from thè skin might diminish ite elasticity; hence, skin collagen changes lead to diminished skin strength.10 Also, dermal collagen becomes stiffer and less pliable during menopause: elastin is more cross-linked and has a higher degree of calcification. Finally, menopause is linked to a drop in die number of dermal blood vessels." © 2009 The North American Menopause Society
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INJTIAL LAPAROSCOPIC ACCESS IN POSTMENOPAUSAL
Ali thcse postmenopausal dermal changes cause thè skin to lose ite tone and elastìcity, resulting in sagging and wrinkling. Consequently, with skin aging, changes in these basic componente of dermal layers lead to functional alteratìons. Nevertheless, HT seems to limit some of thè climacteric aspects of cutaneous aging because estrogen treatment in postmenopausal women has repeatedly been shown to increase collagen content, dermal thickness, and elastìcity. Data on thè effect of estrogen on skin water content are also promising.12 A study showed thè improvements in women undergoing HT in terms of parameters involved in skin aging, as compared with baseline data. Although skin aging is no indicatìon of systemic hormone supplementatìon, a positive effect on aging skin can be observed in women undergoing HT, and estrogens may play a beneficiai role in cutaneous injury repair.13 Moreover, because capillary blood flow velocity decreases significantly in postmenopausal women, estrogen treatments for menopause seem to positìvely modify ite effects on thè basic components of thè skin, as well as on thè more complex structures residing in thè skin, consequently delaying thè skin aging process.10 When envisaging laparoscopy in postmenopausal women, this evidence may be important. In faci, consideration of such skin changes in aging, that is, reduction of thickness and elastìcity, may be helpful in proposing a safe and feasible laparoscopie access that will minimize any complications related to thè skin aging process. In fact, a surgeon using thè blind Veress approach through thè umbilical scar in postmenopausal women could encounter an inelastic atrophic skin, that is highly extensible, fragile, and susceptible to trauma, leading to more lacerations and bruising. The dry skin with deficient elastìcity due to atrophy of dermal collagen and alteratìons of elastìc fibers does not offer adequate resistance to thè Constant axial penetratìon force applied by surgeons to a small blìnd instrument, such as thè Veress needle. A large optìcal instrument, such as thè optical trocar, could be more safely introduced in these conditions because of ite physical action. Major vascular injurics may also be directly recognized by direct visualizatìon of either retroperitoneal hematoma or free blood in thè abdominal cavity. Also, minor injuries, less common in thè DOA access group, cannot be immediately recognized in thè classic closed Veress needle method because a few minutes ìs needed before trocar insertion to adjust to thè pneumoperitoneum. If these minor injuries do not spontaneously resolve within thè first minutes of thè operation, they might complicate thè laparoscopie procedure, lengthening ite total time. Minor injuries mostly present in thè second group are probably linked to excessive force applied by gynecologists, as mentioned above, to introduce a small device—thè Veress needle—in thè female abdominal cavity, regardless of thè reduced elastìcity and greater stiffhess of thè postmenopausal umbilical scars. Needle introduction is not balanccd by thè correct umbilical robustness, as in young women.
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Some researchers concluded that topical estrogen not only increases thè collagen content, as measured in skin hydroxyproline but also causes an increase in collagen synthesis, as was apparent by thè increase in thè levels of thè carboxyl terminal propeptìde of human type I procollagen and of thè amino terminal propeptìde of human rype IH procollagen.14 Based on these findings, to avoid thè issue of aged postmenopausal umbilical tìssue, further research could be focused on thè topical intraumbilical application of estrogens in presurgical assessment. Human studies bave shown that topical estrogens increase dermal hydroscopic qualities15; Maheux et al16 studied postmenopausal nuns and showed that in thè group treated with orai conjugated estrogens, there was a significant increase in skin thickness and skin dermis. Because skin aging is not an indication of systemic hormone supplementatìon, to solve thè problem of blind Veress introduction in postmenopausal dry and atrophic skin, a positive effect on aging skin could result from intraumbilical topical estrogen application. To minimize access method complications, such as bowel injuries unrecognized at thè time of thè first blind access procedure, optically guided trocars were designed to decrease thè risk of injury to intra-abdominal structures.17 The DOA technique illustrated by thè authors is characterized by direct visualizatìon of abdominal wall layers durìng their penetration,18 and thè intraumbilical site represente thè thinnest point of thè intra-abdominal wall with a firmly adherent underlying peritoneum, thus making it less likely for thè optical bladeless trocar to falsely enter thè preperitoneal space.19'20 As reported in this preliminary comparison, thè purpose of this research was to prove that DOA, through insertion of thè trocar under visualizatìon of thè anatomie layers and without prior creation of a pneumoperitoneum, could be a safe and feasible alternative to other more diffused entry modes, such as thè classic closed Veress needle approach, followed by pneumoperitoneum and trocar insertion, in postmenopausal women. In fact, in this investigation, thè DOA method, based on thè new optically guided trocars that avoid both blind access or thè open technique by means of a minilaparotomy, has some statistical advantages because of faster and safer visual direct entry with fewer minor vessel injuries, notwithstanding thè possible limitatìons of this investìgatìon, such as limited number of study participants, racial homogeneity, restricted body mass index, methods of entry provided only by residente, and so on. The literature does not offer comparìsons between these two approaches. Conversely, there are studies on other entry methods, such as open laparoscopy, described by Hasson,21 or thè closed-entry technique by direct access,22 or thè Veress needle.**'23 In fect, a recent study by Ahmad et al,7 based on thè prevalence of first-entry methods in laparoscopy, evaluatìng me practìce of gynecologìsts in thè United Kìngdom revealed that thè closed Veress needle entry technique was used by 93.8% of rispondente; alternative methods including Menopause, Voi. 16, No. 5, 2009
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thè open technique were only used by 5.2% of surgeons. Direct entry was used by 1.1% of respondents, with no mentìon of DOA.7 As a result of these consideratìons on abdominal laparoscopie access, thè findings of this prelirainary study suggest that thè DOA technique might represent in postmenopausal women not undergoing HT a safe and less time-consuming approach to abdominal entry, avoiding thè risks of blind access laparoscopy. However, these data are stili preliminary in terms of clinical morbidity, and to date there are no sufficient randomized studies on thè safety of DOA. CONCLUSIONS According to experimental findings and collected data, thè DOA technique might represent, in postmenopausal women undergoing laparoscopy, a safe and feasible alternative approach to direct and safe abdomen entry without creation of a prepneumoperitoneum. Nevertheless, thè final decision as to which entry technique is to be routinely used should be left to thè surgeon, based on his or her personal experience and capability of swapping thè laparoscopie access with another technique. In feci, in our opinion, thè DOA approach should not be recommended to young surgeons or trainees. Acknowledgments: We thank fmf. Maria Rosaria Buri, professional translator/conference interpreter of thè International Association of Conference Interpretere and a university researcher in translation studies.
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5. Vilos GA. The ABC of a safer laparoscopie entry. J Miniiti Invasive Gynaecol 2006; 13:249-251. 6. Kajoo P, Cooper M, Molloy D. A survey of entry techniques and eomplications of members of thè Australian Gynecological Endoscopy Society. Ausi NZJObstet Gynecol 2002;42:264-266. 7. Ahmad O, Dufly JMN, Watson AJS. Laparoscopie entry techniques and Complications. Int J Gynecol Obstet 2007;99:52-55. 8. Sumino H, Ichikawa S, Abe M, et al. Effects of aging and postmenopausal hypoestrogenism on skin elastieity and bone minerai density in Japanese women. Endoar J 2004;51:159-164. 9. Vetdkt-Sé.'mun S. Effect of estrogena on skia agmg and thè potóntial role of selectìve estrogen rcccptor modulatori. Climacteric 2007; 10: 289-297. 10. Raine-Fenning NJ, Brincat MP, Muscat-Baron Y. Skin aging and menopause: implications for treatment. Am J din Dermatol 2003;4:371 -378. 11. Castelo-Branco C, Duran M, Gonzales-Merlo J. Skin collagen and bone changes related to age and honnone replacement therapy. Maturitas 1992;14:113-119. 12. Brincat MP. Oestrogens and thè skin. J Cosmet Dermatol 2004;3:4l-49. 13. Sator PO, Sator MO, Schmidt JB, et al. A prospectìve, randomized, double-blind, placebo-controlled study on thè influence of a honnone replacement therapy on skin aging in postmenopausal women. Climacterìc 2007;! 0:320-334. 14. Varila E, Rantala I, Oikarinen A, et al. The effect of topica! oestradiol on skin collagen of postmenopausal women. Br J Obstet Gynaecol 1995; 120:985-989. 15. Contet-Audonneau IL, Jeanmaire C, Pauly G. A histological study of human wrinkle structures: comparìson between sun-exposed areas of thè face, with or without wrinkles, and sun-protectcd areas, Br J Dermatol 1999;140:1038-1047. 16. Maheux R, Naud F, Rioux M et al. A randomized, douWe-blind, placebo-controlled study on tfae effect of conjugated estrogens on skin mickness. Am J Obstet Gynecol 1994;170:642-649. 17. Philips PA, Amarai JF. Abdominal access Complications. J Am Coli 5u^2001;I92:525-536. 14. Sharp HT, Dodson MK, Draper ML, Wans DA, Doucette RC, ìtarà WW. Complications associateti with optical-access laparoscopie trocars. Obst Gynecol 2002;99:553-555. 19. Testut L, Jacob O. Trattato di Anatomia Topografica: Le pareti dell'addome, Torino, Italy: UTET, 1977. 20. Rouviere H. In: Cordier G, Delmas A, eds. Anatomie Humaine Descriptìve e Topographique, 9lh ed. In: Cordier G, Delmas A, eds. Paris: Masson, 1962. 21. Hasson HM, Rotman C, Rana N, Kumari NA. Open laparoscopy: 29year experience. Obstet Gynecol 2000:96:763-766. 22. Agresta F, De Simone P, Ciardo LF, Bedin N. Direct trocar insertìon vs Veress occdlc in nonobese patients undergoing laparoscopie procedurcs: a randomized prospectìve single-center study. Surg Erniose 2004;18: 1778-1781. 23. Bonjer HJ, Hazebroek EJ, Kazemier G, Giuffrida MC, Meijer WS, Lange JF. Open versus closed establishment of pneumoperitoneum in laparoscopie sui^eiy. BrJSurg 1997;84:599-602.
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Copyright © 2009 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.
