evaluation of sprayshield™ adhesion barrier in a single center: randomized controlled study in 15...

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Arch Gynecol ObstetDOI 10.1007/s00404-014-3251-3

GenerAl GynecOlOGy

Evaluation of SprayShield™ Adhesion Barrier in a single center: randomized controlled study in 15 women undergoing reconstructive surgery after laparoscopic myomectomy

Garri Tchartchian · Andreas Hackethal · Anja Herrmann · Bernd Bojahr · Christian Wallwiener · Ralf Ohlinger · Andreas D. Ebert · Rudy Leon De Wilde

received: 22 november 2013 / Accepted: 3 April 2014 © Springer-Verlag Berlin Heidelberg 2014

8–12 weeks after myomectomy to evaluate adhesion formation.Main outcome measures Main outcome measures were incidence, severity, and extent of uterine adhesions.Results no significant differences were found between the two study groups.Conclusions SprayShield™ is easy to use. no serious adverse event related to SprayShield™ was observed. effi-cacy data are inconclusive regarding the performance of SprayShield™. Further studies are needed to better under-stand this performance.

Keywords SprayShield™ Adhesion Barrier · Adhesion · laparoscopy · Myomectomy

Introduction

Adhesions are a major cause of chronic, recurrent pelvic pain, and infertility in a significant percentage of surgical

Abstract Objective The objective of this study was to evaluate the safety and efficacy of SprayShield™ Adhesion Barrier in preventing and/or reducing postoperative adhesion during gynecological surgery.Design This was a prospective, controlled, blinded, and randomized study. Patient blinding was performed intraoperatively. Subjects were randomly assigned to the SprayShield™ or the control group in a 2:1 ratio.Setting The study was conducted at the clinic of Gynaecol-ogy and Obstetrics, at the University Hospital for Gynecology in Germany.Patients Fifteen patients participated in this study; nine patients were assigned to the SprayShield™ and six patients to the control group.Interventions During first operation (Fll) in the SprayShield™ group, the agent was applied to all myomec-tomy suture lines. Patients in the control group did not receive any anti-adhesion treatment, only good surgical practice. A second-look laparoscopy (Sll) was performed

G. Tchartchian · B. Bojahr Klinik für Minimal Invasive chirurgie, 14129 Berlin-Zehlendorf, Germany

A. Hackethal Zentrum für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Gießen und Marburg GmbH, 35392 Giessen, Germany

A. Herrmann · r. l. De Wilde (*) clinic of Gynecology, Obstetrics and Gynecological Oncology, University Hospital for Gynecology, School of Medicine and Health Sciences, carl von Ossietzky University Oldenburg, Pius-Hospital, Georgstreet 12, 26121 Oldenburg, lower Saxony, Germanye-mail: [email protected]

c. Wallwiener Abteilung für Geburtshilfe und Gynäkologie, TU München, 81675 Munich, Germany

r. Ohlinger Universitätsklinikum Greifswald Klinik für Frauenheilkunde und Brustzentrum, 17489 Greifswald, Germany

A. D. ebert Deutsches endometriosezentrum Berlin, Vivantes Humboldt-Klinikum, 13509 Berlin, Germany

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patients [1]. Adhesions also have major financial implica-tions as well; in the United Kingdom alone, adhesion for-mation related readmissions following lower abdominal surgery account for costs over 500 million pounds over a 10-year period [2]. Though many different materials have been evaluated for the potential ability to prevent adhesion formation up to this day, the need for comprehensible, site-specific protection remains strong [3–5]. SprayShield™ Adhesion Barrier has been developed as a product to be sprayed onto adhesiogenic tissues. It is a site-specific adhe-sion barrier that solidifies within seconds of being applied onto tissues and is intended to protect tissues from adhe-sion formation during tissue healing [6].

The SprayShield™ Adhesion Barrier System has been shown to reduce the number as well as the affected area of adhesions to injured sites in comparison to control (good surgical practice) [6]. To further evaluate the ability of SprayShield™ Adhesion Barrier to reduce adhesions follow-ing gynecological surgery, a single centre, single-blinded, randomized controlled study was undertaken comparing SprayShield™ Adhesion Barrier to good surgical technique alone (control group) in subjects undergoing laparoscopic myomectomy. Due to the vote of the ethical committee con-cerning second-look laparoscopy, only a low number of par-ticipants could be taken into this first orientating study: the presented results are therefor only low numbered.

Materials and methods

Participants and study settings

eligible participants were all women aged 18 and older, of child-bearing potential, who were scheduled to undergo laparoscopic myomectomy due to at least one myoma, met the eligibility criteria and signed an informed consent. exclusion criteria were pregnancy or lactation, prior open or closed myomectomy for treatment of myomas, evidence of current active endometriosis or infection, history of or active inflammatory bowel disease or pelvic inflammatory disease and presence of a frozen pelvis, or hydrosalpinges. The study has been approved by the local research ethics committee and was conducted at the clinic of Gynaecology and Obstetrics, at the University Hospital for Gynecology in Germany from november 2008 to May 2009.

Trial design

This was a prospective, single centre, controlled, single-blinded, randomized study. Subjects were randomly assigned in a 2:1 ratio to the SprayShield™ Adhesion Barrier group or the control group according to a computer-generated alloca-tion schedule. Patient blinding was performed intraoperatively

through a third person with externally prepared randomization using envelopes. To blind the reviewer to subject and treat-ment, all videos were assigned a unique blind code.

The SprayShield™ Adhesion Barrier System (covidien, Waltham, MA) includes a polymer kit and a laparoscopic air-assisted spray applicator. The SprayShield™ Adhesion Barrier polymer kit contains two solutions, a polyethylene glycol (PeG) ester trylisine amine solution and a borate buffer solution referred to as the blue and the clear precur-sors, respectively. When sprayed, the blue and clear precur-sors react in situ in an electrophilic–nucleophilic reaction, causing the PeG molecules to cross-link and form a hydro-gel within seconds with no heat evolving and no external energy source required (i.e., light source). Within 7 days of application, the hydrogel hydrolyzes and the individual components (PeG and Trylisine) are readily absorbed into the circulatory system and excreted via renal filtration [6].

Interventions

Myomectomies were performed using a subperitoneal 2.0 vicryl thread with a standardized technique as used in multiple adhesion prophylaxis studies [7]. In sub-jects randomized to the SprayShield™ Adhesion Barrier group, SprayShield™ Adhesion Barrier was applied to all myomectomy suture lines [7] and all other areas surgically treated, using not more than one kit [8]. A second-look lap-aroscopy (Sll) was performed 8–12 weeks after myoma enucleation to evaluate adhesion formation. Second-look laparoscopy was performed to evaluate the adhesion forma-tion and, in case of existing adhesions, to perform adhesi-olysis in patients still wanting to conceive.

Both the myomectomy procedure and the Sll were recorded. In this respect, the videos were then edited to remove the phase of the SprayShield™ Adhesion Barrier application from treated subjects and all videos were assigned a unique code to blind the reviewer. The videos were then sent to an independent gynecological surgeon to obtain a standardized, unbiased evaluation of adhesion formation.

Outcome

The primary outcome with respect to efficacy was the incidence (number of adhesions from the uterus to other anatomical structures), extent (1 = covering <25 % of locations total area; 2 = covering 26–50 % of total area; 3 = covering >51 % of total area), and severity (1 = filmy, avascular; 2 = vascular and/or dense; 3 = cohesive) of adhesions scored by a single reviewer. The area of the uterus covered by adhesions was also assessed. Safety eval-uations included the following parameters: adverse events, clinically abnormal laboratory, and coagulation assessment.

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Statistical methods

The primary endpoint was the incidence, extent, and the severity of adhesions. We calculated means and standard deviations and used a two-sample t test to identify differ-ences in means between participants in each group. In addi-tion, we used the two-sided Fisher’s exact test to assess differences between SprayShield™ Adhesion Barrier and control in the proportion of subjects. p < 0.05 was con-sidered significant for all comparisons. Statistical analy-ses were performed using SPSS for Windows (SPSS 16.0, SPSS, Inc., chicago, Il).

Results

Participants

Age-eligible participants were recruited from november 2008 to March 2009. Fifteen patients were included in this study, two patients (one of each study group) withdrew informed consent prior to second-look laparoscopy. Thus, data from 13 patients were available for analysis (flowchart was omitted).

Patients’ demographics and baseline data

Patients’ demographics and baseline characteristics are shown in Table 1. The groups were similar with respect to race, weight, height, medical history, and previous abdomi-nal or pelvic surgeries. Differences between groups were observed in age, gravidity, and vaginal deliveries.

First‑look laparoscopy

Findings of the first-look laparoscopy with myomectomy are presented in Table 2. There were no statistical signifi-cant differences between the SprayShield™ Adhesion Bar-rier group and the control treatment group.

One serious procedure-related adverse event occurred in the control group. A patient with a history of epilepsy experienced increased c-reactive protein level and an epi-leptic seizure postmyomectomy. Problems resolved without sequelae.

SprayShield™ Adhesion Barrier application was easy and without any complications. The assisted sprayer never clogged during use, one kit (10 ml) was used during each surgery in the SprayShield™ Adhesion Barrier group. The total application time was 4.9 ± 1.3 min with a total

Table 1 Demographic data and baseline characteristics

a Values are mean ± SDb not significant

characteristic SprayShield™ Adhesion Barrier group (n = 9)

control group (n = 6)

p value

Age, yearsa 35.8 ± 4.6 44.3 ± 3.3 0.002

Gravidity, na 0.2 ± 0.7 1.5 ± 1.2 0.021

Vaginal deliveries, na 0.2 ± 0.7 1.3 ± 1.2 0.038

caesarian deliveries, na 0.0 ± 0.0 0.0 ± 0.0 –

Weight, kga 70.72 ± 13.04 68.33 ± 8.21 0.698b

Height, cma 168.2 ± 7.0 170.3 ± 3.3 0.506b

race, caucasian, n (%) 9 (100) 6 (100)

Previous/current medical history 0.089b

no, n (%) 8 (88.9) 2 (33.3)

yes, n (%) 1 (11.1) 4 (66.4)

cnS disease, n (%) 1 (11.1) 2 (33.3)

Gynecologic/reproductive, n (%) 0 3 (50)

Other 0 1 (16.7)

Previous abdominal or pelvic surgeries 1.000b

no, n (%) 5 (55.6) 3 (50)

yes, n (%) 4 (44.4) 3 (50)

Adnexal surgery, n (%) 3 (33.3) 2 (33.3)

Other 3 (33.3) 1 (16.7)

reason for surgery

Myoma, n (%) 9 (100) 6 (100)

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Table 2 characteristics of first-look laparoscopy



p value

ASA score, n (%)

I 1 (11.1) 1 (16.7) 1.000b

II 8 (88.9) 5 (83.3)

III 0 (0.0) 0 (0.0)

IV 0 (0.0) 0 (0.0)

Surgery time, mina 99.9 ± 28.9 88.2 ± 26.7 0.443b

Pre-existing adhesions

yes, n (%) 6 (66.7) 3 (50.0) 0.622b

no, n (%) 3 (33.3) 3 (50.0)

Where adhesions lysed?

yes, n (%) 6 (100.0) 3 (100.0) –

no, n (%) 0 (0.0) 0 (0,0)

nA, n (%) 3 3

Volume of irrigation fluids in, mla 911.1 ± 266.7 1,000.0 ± 0.0 0.347b

Volume of irrigation fluids out, mla 855.6 ± 265.1 941.7 ± 20.4 0.360b

Volume of irrigation fluids remaining, mla 55.6 ± 16.7 58.3 ± 20.4 0.777b

Were all fluids suctioned at the end of procedure?

yes, n (%) 9 (100.0) 6 (100.0) –

no, n (%) 0 (0.0) 0 (0.0)

endometriosis?

yes, n (%) 2 (22.2) 1 (16.7) 1.000b

no, n (%) 7 (77.8) 5 (83.3)

Overall stage of endometriosis, n (%)

I 1 (50.0) 0 (0.0) 1.000b

II 1 (50.0) 1 (100.0)

III 0 (0.0) 0 (0.0)

IV 0 (0.0) 0 (0.0)

nA 7 5

Blood lost during surgery?

yes, n (%) 2 (22.2) 1 (16.7) 1.000b

no, n (%) 7 (77.8) 5 (83.3)

estimation of blood loss, mla 5.6 ± 11.3 8.3 ± 20.4 0.739b

received blood transfusion 1.000b

yes, n (%) 0 (0.0) 0 (0.0)

no, n (%) 9 (100.0) 6 (100.0)

Method of hemostasis 1.000b

electrocautery, n (%) 9 (100.0) 6 (100.0)

number of myomas removeda 1.6 ± 0.9 1.8 ± 1.0

1, n (%) 6 (66.7) 3 (50.0)

2, n (%) 1 (11.1) 1 (16.7)

3, n (%) 2 (22.2) 2 (33.3)

Type of myomas removed, n (%)

Intramural 9 (100.0) 6 (100.0)

Subserosal 1 (11.1) 1 (16.7)

Submucosal 0 (0.0) 1 (16.7)

Diameter of myoma, cma 4.57 ± 1.52 4.53 ± 1.19

Size of incision, cma 4.31 ± 0.97 5.03 ± 1.13

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volume of 5.0 ± 0.0 ml used of blue and of clear liquid each. The maximum intraperitoneal pressure during use of the laparoscopic sprayer was 13.8 ± 1.9 mmHg. In every single case, SprayShield™ Adhesion Barrier conformed and adhered to the organs to which the agent was applied.

SprayShield™ Adhesion Barrier was applied to the ante-rior uterus [n = 5 (55.6 %)], the left fallopian tube [n = 2 (22.2 %)], the left abdominal wall [n = 5 (55.6 %)], the left ovary [n = 2 (22.2 %)], the posterior uterus [n = 7 (77.8 %), and the right abdominal wall (n = 3 (33.3 %)].

Second‑look laparoscopy

The second-look laparoscopy revealed no remaining SprayShield™ Adhesion Barrier at treated sites or areas other than treated sites.

Mean time between first-look and second-look laparoscopy was 65.6 ± 6.8 days for the SprayShield™ Adhesion Barrier group and 66.6 ± 7.0 days for the control group (p = 0.808).

Table 3 summarizes the results with regard to adhe-sions to the uterus. none of the results are statistically significantly different between the SprayShield™ Adhe-sion Barrier group and the control treatment group; these include the mean number of sites adherent to the uterus (Fll: 0.5 ± 1.1 versus 0.0 ± 0.0; Sll: 1.1 ± 1.0 versus 0.6 ± 0.9), the mean severity of sites adherent to the uterus (Fll: 0.29 ± 0.55 versus 0.0 ± 0.0; Sll: 1.63 ± 1.06 versus 0.8 ± 1.1), the mean extent score of sites adherent to the uterus (Fll: 0.42 ± 0.85 versus 0.0 ± 0.0; Sll: 0.92 ± 0.66 versus 0.6 ± 0.89), and the mean area of sites adherent to the uterus (cm2) (Fll: 4.13 ± 9.03 versus 0.0 ± 0.0; Sll: 2.19 ± 2.32 versus 2.7 ± 5.24).

Of the 13 analyzed patients, 6 patients (75.0 %) in the SprayShield™ Adhesion Barrier group exhibited adhe-sion in the Fll, and 1 patient (12.5 %) in the Sll. Three patients (60.0 %) from the control group exhibited adhe-sions in the Fll, and one patient (20.0 %) in the Sll. Both

patients exhibited adhesions in the Sll from the left fal-lopian tube to the large bowel. Additionally, an adhesion from the left pelvic sidewall to the left ovary was discov-ered in the SprayShield™ Adhesion Barrier group patient.

Pictures of the results at first-look laparoscopy and second-look laparoscopy are shown in Fig. 1a (first-look laparoscopy before surgery), Fig. 1b (first-look laparoscopy after surgery) and Fig. 2 (Second-look laparoscopy in control group).

The lack of any statistically significant results may be due to the study’s small sample size and consequent lack of statistical power.

Discussion

Adhesions are the most frequent complications of abdomi-nopelvic surgery [8] and can lead to serious complica-tions including infertility, chronic debilitating pain, and a life-time risk of small bowel obstruction with considerable morbidity and mortality [9–11]. Adhesions increase the risk of admission to hospital for related complications follow-ing gynecological procedures [12], and up to 56 % of all patients are in need of further surgery [13].

Myomectomy is particularly compromised by a sig-nificant rate of de novo adhesion formation [7, 14–16]. Patients undergoing posterior myomectomy are most at risk of adhesion formation, with high possible rates of adhesion formation to the posterior wall of the uterus, the rectosig-moid, and the adnexa [17–19].

The rate of patients presenting adhesions after myomec-tomy via laparotomy has been reported to be up to 71–100 % [20–22]. This rate is lower after laparoscopic myomectomy [17, 23, 24]. Frequency of uterine and de novo adhesion formation after laparoscopic myomectomy was reported to be 36.7 % and, respectively, 8.9 % [13]. This explains that, in our low number collective of patients, the control group could present with no adhesions at Sll.

Table 2 continued



p value

number of incisions, n (%)

1 7 (77.8) 3 (50.0)

2 1 (11.1) 1 (16.7)

3 1 (11.1) 2 (33.3)

Adverse events, n (%) 0 (0.0) 1 (16.7) 0.400b

Serious adverse events, n (%) 0 (0.0) 1 (16.7) 0.400b

Device related adverse events, n (%) 0 (0.0) 0 (0.0) 0.400b

Procedure-related adverse events, n (%) 0 (0.0) 1 (16.7) 0.400b

a Values are mean ± SDb not significant

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A variety of adhesion prophylactics have been inves-tigated to reduce occurrence and severity of adhesion formation. The installation of lactated ringer’s solution

at the end of surgery is used to produce a hydrofloata-tion effect. However, meta-analysis showed no increased adhesion-free outcome [25]. Adept®, a 4 % Icodextrin

Table 3 results of adhesions to the uterus during Sll

Parameter SprayShield™ Adhesion Barrier group (n = 8)


p value

number of sites adherent to the uterus

Fll

Mean ± SD 0.5 ± 1.1 0.0 ± 0.0

Median 0.0 0.0

Minimum–maximum 0–3 0–0

Sll

Mean ± SD 1.1 ± 1.0 0.6 ± 0.9 0.357

Median 1.0 0.0

Minimum–maximum 0–3 0–2

Mean severity score of sites adherent to the uterus

Fll

Mean ± SD 0.29 ± 0.55 0.0 ± 0.0

Median 0.0 0.0

Minimum–maximum 0.0–1.3 0.0–0.0

Sll

Mean ± SD 1.63 ± 1.06 0.8 ± 1.1 0.205

Median 2.0 0.0


Sll—highest severity score

Mean ± SD 1.63 ± 1.06 1.0 ± 1.41 0.381

Median 2.0 0.0


Mean extent score of sites adherent to the uterus

Fll

Mean ± SD 0.42 ± 0.85 0.0 ± 0.0

Median 0.0 0.0


Sll

Mean ± SD 0.92 ± 0.66 0.6 ± 0.89 0.477

Median 1.0 0.0


Sll—highest extent score

Mean ± SD 1.0 ± 0.76 0.6 ± 0.89 0.404

Median 1.0 0.0


Area of sites adherent to the uterus (cm2)

Fll

Mean ± SD 4.13 ± 9.03 0.0 ± 0.0

Median 0.0 0.0


Sll

Mean ± SD 2.19 ± 2.32 2.7 ± 5.24 0.811

Median 1.5 0.0


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solution, also reduces adhesion formation by prolonged hydro floatation. It is easily applied and has been shown to be effective in reducing postoperative adhesions following

laparoscopy [26]. Hydrogel SprayGel®, which is similar to SprayShield™ Adhesion Barrier, and which forms a solid, flexible, absorbable hydrogel, has demonstrated efficacy in a population of patients known to be particularly at risk of adhesion formation [27]. As SprayShield™ Adhesion Bar-rier consists of a composition of effective substances ana-logue to that of Hydrogel SprayGel®, a positive prophylac-tic effect may be expected.

Adhesion formation during myomectomy occurs due to traumatic manipulation of the uterus with release of adhe-siogenic factors, fibrin deposition on the peritoneal sur-face, local inflammation around the scar and in the area of operation, and exposure of the peritoneum to cO2. Gentle surgery based on basic principles of plastic microsurgery with multi-layer reconstruction of the uterus and inverted sutures has an adhesion-prophylactic effect in itself [8]. The use of intraoperative irrigation with pre-warmed lac-tated ringer´s solution and surgery performed with the least possible blood loss is also helpful in preventing adhesions.

In summary, this study shows that SprayShield™ Adhe-sion Barrier is easy to use. no serious adverse event related to SprayShield™ Adhesion Barrier was observed. The vote of the ethical committee only allowed a low number of patients to recruit for second-look laparoscopy; there-fore only a low number of patients could be evaluated. Due to the low number of patients’ efficacy, data are not final regarding the performance of SprayShield™ Adhesion Bar-rier. Further studies with a larger sample size are needed to better understand this performance.

Acknowledgments This study was sponsored by covidien.

Conflict of interest none.

References

1. Practice committee of the American society for reproductive medicine in collaboration with the society of reproductive sur-geons (2006) Pathogenesis, consequences, and control of peri-toneal adhesions in gynecologic surgery. Fertil Steril 86(Suppl 4):S1–S5

2. Wilson MS, Menzies D, Knight A, crowe AM (2002) Demon-strating the clinical and cost-effectiveness of adhesion reduction strategies. colorectol Dis 4:355–360

3. De Wilde rl, Trew G (2007) Postoperative abdominal adhesions and their prevention in gynecological surgery. Gynecol Surg 4:161–168

4. Mais V, cirronis MG, Peiretti M, Ferrucci G, cossu e, Melis GB (2012) efficacy of auto-crosslinked hyaluronan gel for adhesion prevention in laparoscopy and hysteroscopy: a systematic review and meta-analysis of randomized controlled trials. eur J Obstet Gynaecol reprod Biol 160(1):1–5

5. Brochhausen c, Schmitt VH, Planck cne, rajab TK, Hollemann D, Tapprich c, Krämer B, Wallwiener c, Hierlemann H, Zehbe r, Planck H, Kirkpatrick cJ (2012) current strategies and future

Fig. 1 a Picture of the first-look laparoscopy before surgery. b Pic-ture of the first-look laparoscopy after surgery

Fig. 2 Picture of the second-look laparoscopy in control group

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perspectives for intraperitoneal adhesion prevention. J Gastroin-test Surg 16(6):1256–1274

6. Ferland r, campbell PK (2009) Pre-clinical evaluation of a next-generation spray adhesion barrier for multiple site adhesion pro-tection. Surg Technol Int 18:137–143

7. Trew G, Pistofidis G, Pados G, lower A, Mettler l, Wallwie-ner D, Korell M, Pouly Jl, coccia Me, Audebert A, nappi c, Schmidt e, McVeigh e, landi S, Degueldre M, Konincxk P, rim-bach S, chapron c, Dallay D, röemer T, Mcconnachie A, Ford I, crowe A, Knight A, Dizerega G, Dewilde r (2011) Gynaecologi-cal endoscopic evaluation of 4% icodextrin solution: a european, multicentre, double-blind, randomized study of the efficacy and safety in the reduction of de novo adhesions after laparoscopic gynaecological surgery. Hum reprod 26(8):2015–2027

8. De Wilde rl, Trew G (2007) Postoperative abdominal adhesions and their prevention in gynaecological surgery: expert consensus position. Part 1 & 2—steps to reduce adhesions. Gynecol Surg. Gynecol Surg 4:243–253

9. ellis H (1971) The cause and prevention of postoperative intra-peritoneal adhesions. Surg Gynecol Obstet 133(3):497–511

10. ten Broek rPG, Issa y, van Santbrink eJP, Bouvy nD, Kruit-wagen rFPM, Jeekel J, Bakkum eA, rovers MM, van Goor H (2013) Burden of adhesions in abdominal and pelvic sur-gery: systematic review and met-analysis. BMJ 347:f5588. doi:10.1136/bmj.f5588

11. Okabayashi K, Ashrafian H, Zacharakis e, Hasegawa H, Kita-gawa y, Athanasiou T, Darzi A (2013) Adhesions after abdomi-nal surgery: a systematic review of the incidence, distribution and severity. Surg Today. [epub ahead of print]

12. lower AM, Hawthorn rJ, clark D, Boyd JH, Finlayson Ar, Knight AD, crowe AM, Surgical and clinical research Group (2004) Adhesion-related readmissions following gynecological laparoscopy or laparotomy in Scotland: an epidemiological study of 24,046 patients. Hum reprod 19(8):1877–1885

13. ellis H, Moran BJ, Thompson Jn, Parker Mc, Wilson MS, Men-zies D, McGuire A, lower AM, Hawthorn rJ, O’Brien F, Buchan S, crowe AM (1999) Adhesion related hospital readmissions after abdominal pelvic surgery: a retrospective cohort study. lan-cet 353:1476–1480

14. Jin c, Hu y, chen Xc, Zheng Fy, lin F, Zhou K, chen FD, Gu HZ (2009) laparoscopic versus open mymectomy: a meta-analy-sis of randomized controlled trials. eur J Obstet Gynecol reprod Biol 145(1):14–21

15. Kasum M (2009) Fertility following myomectomy. Acta clin croat 48:137–143

16. Wallwiener M, Brölmann H, Koninckx Pr, lundorff P, lower AM, Wattiez A, Mara M, De Wilde rl (2012) Adhesions after abdominal, pelvic and intra-uterine surgery, and their prevention. Gynecol Surg 9:465–466

17. Takeuchi H, Kinoshita K (2002) evaluation of adhesion forma-tion after laparoscopic myomectomy by systematic second-look microlaparoscopy. J Am Assoc Gynecol laparosc 9(4):442–446

18. Takeuchi H, Kitade M, Kikuchi I, Shimanuki H, Kumakiri J, Kinoshita K (2005) Adhesion-prevention effects of fibrin sealants after laparoscopic myomectomy as determined by second-look laparoscopy. J reprod Med 50(8):571–577

19. Hirschelmann A, Tchartchian G, Wallwiener M, Hackethal A, De Wilde rl (2012) A review of the problematic adhesion prophylaxis in gynaecological surgery. Arch Gynecol Obstet 285:1089–1097

20. Buletti c, Polli V, negrini V (1996) Adhesion formation after laparoscopic myomectomy. J Am Assoc Gynecol laparosc 3:533–536

21. Myomectomy Adhesion Multicenter Study Group (1995) An expanded polytetrafluoroethylene barrier (gore-tex surgical mem-brane) reduces post-myomectomy adhesion formation. Fertil Steril 63:491–493

22. Tulandi T, Murray c, Guralnick M (1993) Adhesion formation and reproductive outcome after myomectomy and second look laparoscopy. Obstet Gynecol 82:213–215

23. Dubuisson J-B, Fauconnier A, chapron c, Kreiker G, nörgaard c (1998) Second look after laparoscopic myomectomy. Hum reprod 13(8):2102–2106

24. Di Gregorio A, Maccario S, raspollini M (2002) The role of lap-aroscopic myomectomy in women of reproductive age. reprod Biomed Online 4(Suppl 3):55–58

25. Wiseman DM, Trout Jr, Diamond MP (1998) The rates of adhe-sion development and the effects of crystalloid solutions on adhe-sion development in pelvic surgery. Fertil Steril 70(4):702–711

26. Di Zerega GS, Verco SJ, young P, Kettel M, Kobak W, Martin D, Sanfilippo J, Peers eM, Scrimgeour A, Brown cB (2002) A ran-domized, controlled pilot study of the safety and efficiacy of 4% Icodextrin solution in the reduction of adhesions following lapa-roscopic gynaecological surgery. Hum reprod 17(4):1031–1038

27. Mettler l, Audebert A, lehmann-Willenbrock e, Schive-Peter-hansl K, Jacobs Vr (2004) A randomized, prospective, con-trolled, multicenter clinical trial of a sprayable, site-specific adhe-sion barrier system in patients undergoing myomectomy. Fertil Steril 82(2):398–404

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evaluation of sprayshield™ adhesion barrier in a single center: randomized controlled study in 15...

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