UNIVERSITTSKLINIKUM

Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
How to prevent tissue adhesions in
gynecological endoscopic surgery
Liselotte Mettler
Department of Obstetrics and Gynecology
Kiel School of Gyne. Endoscopy
University of Schleswig-Holstein,Campus Kiel
Kiel, Germany
lmettler@email.uni-kiel.de
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
From Kiel,
Germany
To
Singapore
SICOG 2013
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KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Adhesions:
Do we need to prevent?
Yes!
Do we need to treat?
Yes?
UNIVERSITTSKLINIKUM
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KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Paradox of surgery
The method proposed to treat adhesions is the one that induces
adhesions.
Need for clinical & cost-effective agents
to reduce adhesion development
UNIVERSITTSKLINIKUM
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Campus Kiel
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Formation of Adhesions
Bleeding
Adhesions
Injury
Fibrin
deposition
Inflammation
Steps to reduce adhesions
during surgery
Increase vascular permeability
Reduce infection risk
Minimize tissue handling
Careful technique
Microsurgery
Reduce drying of tissues
Lubrication
Limit use of cautery
Limit use of sutures
Avoid materials with fibres
Use starch-free gloves
UNIVERSITTSKLINIKUM
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Steps to reduce adhesions
Careful surgical technique
Minimize inflammatory response
Augmentation of fibrinolysis
Adhesion-reduction agents
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Applying adjuvants: solutions / drugs
NSAIDs Non steroidal Anti inflammatory Disease agents
Most widely studied; clinical efficacy is questionable
Corticosteroids
Poor efficacy; associated with immunosuppression and delayed wound healing
Fibrinolytics
Risk of impaired wound healing and/or bleeding
Risberg B. Eur J Surg Suppl. 1997
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Adhesion Reduction Agents: The ideal agent
Safety
Easy to use
General surgery
Gynaecological surgery
Open
Laparoscopic
Efficacy
Operation site
Throughout the cavity
Economical
ESHRE 2002 Survey, EACP 2002 Survey
According to recent surveys of surgeons the four key attributes are:
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Adhesion Reduction Agents
Site Specific
Preclude* expanded polytetrafluoroethylene Gore-Tex sheet Generally unavailable
Interceed oxidised regenerated cellulose
fabric
Seprafilm hyaluronic acid carboxymethylcellulose
film
SprayGel/Shield polyethylene glycol
hydrogel
SurgiWrap copolymer 70:30 Poly(L-lactide-co-D, L-lactide) sheet
Hyacorp endogel Cross linked Sodium hyaluronate
Intercoat Polyethylen oxide (PEO) /sodium carboxymethyl cellulose (CMC), 30 days to clear the
peritoneal cavity
Broad Coverage
Crystalloids Ringers lactate/saline +/- Heparin
Hyskon 32% dextran 70 solution Generally unavailable
Sepracoat 0.04% hyaluronic acid-phosphate-buffered saline Withdrawn
Intergel 0.5% ferric hyaluronate gel Withdrawn
Adept icodextrin 4% solution
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Most Widely Used Adhesion Prevention Adjuvants
Crystalloid instillates
Lactated Ringers
Saline
Hartmanns Solution
Limitations:
Absorbed within 24 hours
They dont prevent adhesions!
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Interceed Barrier
(Oxidized Cellulose, Gynecare)
First FDA approved adhesion reduction adjuvant
Most clinical studies (24)
Widely applicable
all intraperitoneal locations
all surgical procedures
Compatible with laparoscopy
Limited use in colorectal surgery
Limitations:
Blood oozing renders it ineffective
Irrigants must be removed
Technical application challenges!
UNIVERSITTSKLINIKUM
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Seprafilm Membrane
(HA+CMC, Genzyme)
Widely applicable
covers all intraperitoneal locations
all surgical procedures
Used in general surgery
Limitations:
Handling
Residual irrigation fluid must be removed
Cannot be used via laparoscopy
Cost!!
Beck et al Dis Colon Rectum 2003;46:1310-1319
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Polymerization
Methylene blue to show where it is used
SprayGel / Shield (Polyethylene Glycol Polymer, Confluent)
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Laparoscopic Kit
Requires specialised air pump
SprayGel / Shield (Polyethylene Glycol Polymer, Confluent)
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SprayShield(Polyethylene Glycol Polymer, Covidien)
Limitations
complex set-up
time consuming
cost
UNIVERSITTSKLINIKUM
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KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Adept

- new solution to adhesion reduction?

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Adept - icodextrin 4% solution
1,4 linked glucose polymer
Icodextrin 4% solution
isosmolar
biocompatible
well-established safety profile at 7.5% concentration
>36,000 patient years safety data from renal use
~50,000 patients treated with Adept
persists in peritoneal cavity
reduces adhesion formation through physical action
hydroflotation
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Adept hydroflotation mechanism
Residual Volume in Abdomen
0
500
1000
1500
2000
2500
0 20 40 60 80 100 120
Time (hours)
ml
4% icodextrin
Saline
Glucose
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Adept use
Irrigation
minimum 100ml / 30min
Laparoscopy through the scope
Laparotomy via a syringe
Instillation
1000 ml at closure
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Adept (Icodextrin 4%, Baxter Pharmaceuticals)
Covers all intraperitoneal locations
Easy to use
laparotomy registry feedback
Not constrained by oozing
Residual irrigation solution is not a problem
Extensive safety experience at 7.5%
ARIEL Registry of routine use in >4,600 patients
feedback of use and safety good
Modest cost
The first powered RCT providing evidence for the use of Adept for
adhesion prevention
Brown et al.: Adept reduces adhesions after laparoscopic surgery...
Fertil Steril (2007) 88:1413-26
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HYA corp ENDO GEL cross linked Sodium
hyaluronate
Reduces adhesion formation particularly after peritoneal defects
which provoke normally severe adhesion formation with pain and
sometimes bowel obstruction.
Mettler et al. MITAT, 2013 online published
UNIVERSITTSKLINIKUM
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Adopt use of anti-adhesion agents in High Risk surgery
Myomectomy
Suturing and Spray Shield or easier and cheaper Hya-Corp
endogel
Periovarian Adhesions
Remove the ovaries out of this field
Spray Shield or easier and cheaper Hya-Corp endogel in
fossa ovarica
Endometriosis
Adept and Hya-Corp endogel
Adhesiolysis
Adept and Hya-Corp endogel
Easy to use in open surgery, caesarean section,
oncology,etc.
UNIVERSITTSKLINIKUM
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Surgical procedures and adjuvant use
Adhesion
Type
Fertility Surgery Gynaecology General
Surgery
De
novo
Reform Open Laparoscope Open Scope Open Scope
Uterus Adnexa Uterus Adnexa Uterus Adnexa Uterus Adnexa
Site
Specific
Preclude +++ +++
X X X X X X X
Interceed +++ +++

O O
Seprafilm +++ +++
X X X X X X X
SprayGel +++ +++

? ?
SurgiWrap ? ? ? ? ? ? ? ? ? ? ? ?
Broad
Coverage
Hyskon ++ ++ O O O O O O O O O O
Sepracoat ++ ++ Withdrawn
Intergel +++ +++ Withdrawn
Adept +++ +++

O = not used/recommended
UNIVERSITTSKLINIKUM
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KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Informed consent
International Adhesions Society Patient Survey*
In only 10.4% of cases are adhesions mentioned as part of informed
consent process
In 14.4% of cases adhesions discussed but not part of consent
Adhesiolysis patients
54% given some information before surgery
46% given specific information about anti-adhesion agents
In non-adhesiolysis procedures only 10% patients advised about
adhesions
Only 6% given information on anti-adhesion agents
Wiseman, Adhesions News & Views 4 2003 and PAX Meeting 2003
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Adhesions are inevitable
High risk of adhesion-related problems
Small bowel obstruction
Female infertility
Chronic and debilitating pelvic pain
Reoperative complications
Do we tell our patients when we obtain consent?
UNIVERSITTSKLINIKUM
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KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Adoption of routine prophylaxis
depends on impact of strategy on
adhesion-related readmissions
and cost of strategy
Prophylaxis?
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Cost-effectiveness
Menzies, Parker et al. Ann Roy Coll Surg Engl. 2001
Costs of adhesion-related Small Bowel Obstruction
Conservatively treated 1,606 (mean stay 7 days)
Surgically treated 4,677 (mean stay 16 days)
Adhesion reduction technologies may reduce costs
UNIVERSITTSKLINIKUM
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Influence of surgery It's our job
reduce coagulation
reduce bleeding
perform a good approximation (peritoneum)
reduce the use of drainage
Some examples ...
UNIVERSITTSKLINIKUM
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KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Paracervical Fibroid
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Laparoscopic supracervical hysterectomy (LASH)
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Myomectomy anterior wall and fundus uteri
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Myomectomy posterior wall left side
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Myomectomy posterior wall left side
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Adhesiolysis
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Role of laparoscopy in identifying the
clinical significance and cause of
adhesions and chronic pelvic pain: a
retrospective review at the Kiel School of
Gynecological Endoscopy.
JSLS 2007; 11:303-308
L. Mettler and M. Al Hujeily
UNIVERSITTSKLINIKUM
Schleswig-Holstein
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Table 1. Reason for admission vs. presence of adhesions among all patients (n = 462)
Reason for Admission Vs. Presence of Adhesions
Presence of Adhesions
Total
Yes No
Reason for
Admission
Ovarian Surgery 94(34.2%) 61(32.6%) 155(33.5%)
Pelvic Pain 84(30.5%)* 22(11.8%) 106(22.9%)
Myomectomy 37(13.5%) 44(23.5%) 81(17.5%)
Infertility 29(10.5%) 21(11.2%) 50(10.8%)
Tubal Surgery 17(6.2%) 21(11.2%) 38(8.2%)
Hysterectomy 9(3.3%) 7(3.7%) 16(3.5%)
Rest of Procedures 5(1.8%) 11(5.9%) 16(3.5%)
Total 275(100%) 187(100%) 462(100%)
* P < 0.0005
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KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Table 2. Relation between timing and type of the previous surgery among all patients with adhesions (n = 193).
Time Interval of Previous
Surgery
Total
0-5 yrs 5-10 yrs > 10 yrs
Past
Surgical
History
> One Previous
Surgery
9(4.7%) 4(2.1%)
56(29.0%)
*
69(35.8%
)
Appendectomy 2(1.0%) 3(1.6%) 47(24.4%)
52(26.9%
)
Myomectomy 7(3.6%) 3(1.6%) 5(2.6%) 15(7.8%)
Diagnostic
Laparoscopy
6(3.1%) 3(1.6%) 4(2.1%) 13(6.7%)
Ovarian Surgery 2(1.0%) 2(1.0%) 7(3.6%) 11(5.7%)
Tubal Ligation 1(0.5%) 2(1.0%) 4(2.1%) 7(3.6%)
Hysterectomy 1(0.5%) 1(0.5%) 3(1.6%) 5(2.6%)
Ectopic Pregnancy 1(0.5%) 0(0.0%) 3(1.6%) 4(2.1%)
Other Surgical
Procedures
1(0.5%) 3(1.6%) 13(6.7%) 17(8.8%)
Total
30(15.5
%)
21(10.9
%)
142(73.6
%)
193(100
%)
*P < 0.0005
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Table 3. Relation between timing and type of the previous surgery among patients with pelvic pain.
Time Interval of Previous Surgery
Total
1-5 yrs
5-10
yrs
> 10 yrs
Past
Surgical
History
> One Previous Surgery 7(10.4%) 1(1.5%) 25(37.3%) 33(49.3%)
Appendectomy 2(3.0%) 0(0.0%) 9(13.4%) 11(16.4%)
Myomectomy 2(3.0%) 1(1.5%) 2(3.0%) 5(7.5%)
Tubal Ligation 1(1.5%) 1(1.5%) 3(4.5%) 5(7.5%)
Diagnostic Laparoscopy 1(1.5%) 0(0.0%) 2(3.0%) 3(4.5%)
Ovarian Surgery 1(1.5%) 0(0.0%) 1(1.5%) 2(3.0%)
Hysterectomy 1(1.5%) 0(0.0%) 0(0.0%) 1(1.5%)
Other Surgical
Procedures
0(0.0%) 1(1.5%) 6(9.0%) 7(10.4%)
Total 15(22.4%) 4(6.0%) 48(71.6%) 67(100%)
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Figure 1. Reason for admission vs. presence of adhesions among all patients (n = 462)
UNIVERSITTSKLINIKUM
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KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Site of Adhesions
M
u
l
t
i

S
i
t
e
s
P
e
l
v
i
s
M
i
d

A
b
d
o
m
e
n
U
p
p
e
r
A
b
d
o
m
e
n
C
o
u
n
t
50
40
30
20
10
0
Type of Adhesions
Thin
Thick
P <
0.005
Figure 3. Relation between the type and site of adhesions among patients with chronic pelvic pain
UNIVERSITTSKLINIKUM
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Let me report on 4 studies, we performed,
investigating adhesion reducing agents
1.COSEAL (BAXTER)
2.ADEPT (BAXTER)
3. SPRAY SHIELD (COVIDIEN)
4. HYA Corp Endogel
(BIO SCIENCE)
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Adhesion Prevention - Does it work?
Objective of the study:
The management of fibroids and the surgical
treatment of endometriosis is closely related to adhesion
prevention, as consecutive adhesions may hinder the
desired aim of the surgery
pain relieve, fertility and conception as much as the
fibroid or endometriosis
UNIVERSITTSKLINIKUM
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Adhesion Prevention - Does it work?
Material and Methods:
In two randomised controlled studies with
SprayShield (COVIDIEN BioSurgery) former SprayGel
and Adhibit/COSEAL (BAXTER) and in one double-
blind randomised controlled study with Adept (
Baxter)
the potential efficacy of the barrier gels and Adept
(0,4% icodextrin solution) to reduce post-operative
adhesions was evaluated.
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Adhesion Prevention - Does it work?
Material and Methods:
After the initial myomectomy or endometrioma
enucleation by operative laparoscopy in trial and control
patients, a second-look laparoscopy was performed 6
8 weeks after the primary surgery to assess the
incidence of new adhesions, their extent and their
tenacity score.
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COSEAL
UNIVERSITTSKLINIKUM
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Human Reproduction Vol. 23, No. 5, pp. 1093-1100,
2008
COSEAL
A Safety and Efficacy Study of a Resorbable Hydrogel
for Reduction of Postoperative Adhesions Following
Myomectomy
Running title: Hydrogel for Adhesion Reduction Post-
Myomectomy
L. Mettler, MD, PhD (1); J. Hucke, MD, PhD (2); B. Bojahr,
MD, PhD (3);
H.-R. Tinneberg, MD, PhD (4); N. Leyland, MD (5); R.
Avelar, MD (6)
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COSEAL -Adhesion Prevention Gel
Component 1
Component 2
PEG Solution
Backbone
Buffer
In Situ Polymerization
F
L
U
I
D
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49
Pre-clinical Safety and Effectiveness Studies
Effectiveness
- Complete
Studies provide evidence that
COSEAL group performed better
than Control group in adhesion
prevention
Safety
- Complete
Cytotoxicity
Sensitization
Implantation
Toxicity
Genotoxicity
ADME Biodegradation
Safety (Pre-Clinical)
- Complete
Reproductive Toxicity (IDE)
Infection Potentiation (IDE)
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Table I: Modified AFS Scoring Method for Adhesions
Finding mAFS Score
Severity Grade
Tenacity None, Extent None 0 None
Tenacity Filmy, Extent < 25% 1 Mild
Tenacity Filmy, Extent 25 50% 2 Mild
Tenacity Filmy, Extent 51% 3 Moderate
Tenacity Dense, Extent < 25% 4 Moderate
Tenacity Dense, Extent 25 50% 5 Severe
Tenacity Dense, Extent 51% 6 Severe
mAFS=modified American Fertility Society
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51
COSEAL
(ITT)
Control
(ITT)
P-value*
Primary surgery 0.5 1.4
(N=48)
0.0 0.0
(N=23)
0.140
Second-look 1.1 1.9
(N=38)
2.6 2.2
(N=20)
0.024
Change from
baseline
0.8 2.0
(N=38)
2.6 2.2
(N=20)
0.010
Change from
baseline, p-value
0.014 < 0.001
Mean mAFS at the Posterior Uterus Site
Cohesion Myomectomy Study
* ANOVA p-values
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52
1st Surgery
COSEAL
(N=38)
Control
(N=20)
P-value*
None 92.1% (35) 100.0% (20) 0.2086
< 25% 2.6% (1) 0.0% (0)
25-50% 5.3% (2) 0.0% (0)
> 51% 0.0% (0) 0.0% (0)
2nd Surgery
None 65.8% (25) 35.0% (7) 0.0277
< 25% 21.1% (8) 30.0% (6)
25-50 % 5.3% (2) 30.0% (6)
> 51% 7.9% (3) 5.0% (1)
Extent Score at the Posterior Uterus Site
Cohesion Myomectomy Study
* Mann-Whitney test p-values
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53
Cohesion Myomectomy Study
2nd Surgery
COSEAL
(N=38)
Control
(N=20)
P-value*
Adhesions 34.2% (13) 65.0% (13) 0.0245
No
adhesions
65.8% (25) 35.0% (7)
* Likelihood-ratio chi-square test p-value (two-sided)
Incidence of Adhesions at the Posterior Uterus Site
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54
Effectiveness Assessment
71% of COSEAL subjects were treated at < 3 of the 15 pelvic
sites.
The vast majority of sites compared between COSEAL and
control were not treated with COSEAL.
However,
Most incisions were located at the posterior uterus from
myoma removal (84.5%)
Almost all randomized COSEAL subjects (47 of 48) received
COSEAL on the posterior uterus
Therefore the primary and secondary endpoints were redirected
to the posterior uterus only.
Coseal Myomectomy Study
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Adhesion Prevention - Does it work?
Results:
Adhibit (COSEAL) applied under air pressure shows a good
trend towards adhesion prevention (>65% efficacy
As the drug went from Cohesion to Angiotech and now to Baxter
as Coseal, which was the original name , the company
plans a new promotion.
Table 3
Adhesion scores exspressed in severity extent and
incidence (0 3) after endoscopic surgery in a second
look endoscopic evaluation
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ADEPT and GENEVA STUDY
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ADEPT and GENEVA STUDY
The Geneva study with Adept has demonstrated with us so far
ONLY in endometrioma surgery a certain adhesion reduction (65%
efficacy).
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Adept and its efficacy
The only statistical differency in a
comparison of Adept to Ringers
lactate was the really better
adhesion protective effect on the
posterior side of the uterus
G. Trew , G. Pistofidis, G. Pados,A. Lower, L. Mettler, D.
Wallwiener et al, Human Reproduction, 2011, Vol.
26,8
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Adept

- new solution to adhesion reduction?

UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Adept - icodextrin 4% solution
1,4 linked glucose polymer
Icodextrin 4% solution
isosmolar
biocompatible
well-established safety profile at 7.5% concentration
>36,000 patient years safety data from renal use
~50,000 patients treated with Adept
persists in peritoneal cavity
reduces adhesion formation through physical action
hydroflotation
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Adept hydroflotation mechanism
Residual VolumeinAbdomen
0
500
1000
1500
2000
2500
0 20 40 60 80 100 120
Time(hours)
ml
4%icodextrin
Saline
Glucose
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Adept use
Irrigation
minimum 100ml / 30min
Laparoscopy through the scope
Laparotomy via a syringe
Instillation
1000 ml at closure
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Adept (Icodextrin 4%, Baxter Pharmaceuticals)
Covers all intraperitoneal locations
Easy to use
laparotomy registry feedback
Not constrained by oozing
Residual irrigation solution is not a problem
Extensive safety experience at 7.5%
ARIEL Registry of routine use in >4,600 patients
feedback of use and safety good
Modest cost
The first powered RCT providing evidence for the use of Adept for
adhesion prevention
Brown et al.: Adept reduces adhesions after laparoscopic surgery...
Fertil Steril (2007) 88:1413-26
Trew et al: GENEVA Study Human Reproduction, Vol 26, 8, 2011
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
SPRAY SHIELD
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Mettler L, Audebert A, Lehmann-Willenbrock E,
Schive-Peterhansl K, Jacobs VR.
A randomized, prospective, controlled,
multicenter clinical trial of a sprayable,
site-specific adhesion barrier system in
patients undergoing myomectomy.
Fertil Steril. 2004; 82(2): 398-404.
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Current uses of PEG
in the body
Eye drops
Pharmaceuticals
Injectables
Surgical sealants
Route of clearance
Kidneys, excreted in urine
Polyethylene glycol (PEG)
Time (hours)
0
20
40
60
80
100
P
e
r
c
e
n
t

r
e
m
a
i
n
i
n
g
0 1 2 3 4 5 6 7
Absorption over 7 days
Then rapid systemic clearance
I-labeled
20k MW PEG
125
Yamaoka, et al: J. Pharm. Sci.,
Vol 83, No. 4, Apr 1994, p 601
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
69
66
3
2
64
54 10
26 C 28 T 4 C 6 T
N=18/30 C
60%
N=22/34 T
64,7%
Number of patients enrolled
withdrawn
Number of patients
in safety evaluation
Excluded prior randomization
Training patients
(one at each site)
(patients who were from the study)
Number of patients randomised and
included in efficacy evaluation
University Frauenklinik
(OB/GYN) Kiel
Bordeaux Clinic
Randomization
distribution
(C=control,
T=treatment)
Returned second-look
laparoscopy
Flow Chart:
Distribution of Patients in the SprayShield Trial
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Treated Group (T) SD Control Group (C) SD
Randomized [n] 34 30
Mean Age [years] 34.9 (28-52) 5.2 35.0 (23-45) 5.9
Mean Height [cm] 168.6 (157.0-179.0) 5.7 168.5 (155.0-180.0) 6.8
Mean Weight [kg] 64.8 (49-90) 9.5 63.6 (44-92.5) 11.8
Prior Myomectomy [n] 5 (14.7%) 1 (3.3%)
Prior Adhesiolysis [n] 3 (8.8%) 0 (0.0%)
Primary Cause of Surgery:
Infertility [n] 11 (32.4%) 9 (30.0%)
Pain [n] 16 (47.1%) 16 (53.3%)
Other [n] 7 (20.6%) 5 (16.7%)
Leiomyoma removed:
Mean Number [n] 2.6 (0-18) 3.2 2.6 (0-14) 3.2
Mean Weight [g] 115.0 (0-452) 121 101.1 (0-520) 104
Uterine Incisions:
Mean Number [n] 1.9 (1-8) 1.5 1.5 (1-6) 1.2
Mean length [cm] 7.4 (3-28) 4.9 7.0 (3-26) 4.6
Completed Second-Look
Laparoscopy [n]
22 (64.7%) 18 (60.0%)
Patient Demographics
for Treatment and Control Groups
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Schedule of Events
Informed Consent
Medical History
Physical Exam
Pregnancy Test
Patient Weight
Adverse Events
Concomitant
Medication
Health questions
Blood Chemistry
Urinalysis
Pre-
Op
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Phon
e call
2nd Look
Laparosco
py
Exam
Discharg
e
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Polymerization
Methylene blue to show where it is used
SprayGel / Shield (Polyethylene Glycol Polymer, Confluent)
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Laparoscopic Kit
Requires specialised air pump
SprayGel / Shield (Polyethylene Glycol Polymer, COVIDIEN)
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
SprayShield(Polyethylene Glycol Polymer, Covidien)
Limitations
complex set-up
time consuming
cost
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Adhesion Prevention - Does it work?
Both adhaesion barrier gels
SpryShield and Coseal were
safe,well tolerated and
demonstrated efficacy in a
population of patients at risk for
adhesion formation.
Adept -was safe AND WAS
APPLIED WITHOUT SIDE
EFECTS
Mettler et al. Fertil,Steril.
2004
Mettler et al. Human
Reproduction, 2008
Trew et al. Human
Reprod.2011
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
HYA corp Endo Gel
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
HyaCorp Endo Gel
Represents a Hyaluronic Acid (HA) and sodium
carboxymethylcellulose (CME) lyophilized solution crosslinked with
1.ethyl-3-(3-dimethylaminopropyl) carbodiimide
which proved to be an excellent Anti-Adhesion Barrier Gel in animal
studies since 5 years :
Sang-Mook Lee et al. The effects of Hyaluronic acid-
carboxymethylcellulose membraner (Guardix-MB) barriers on
prevention of post-operation peritoneal adhesions : Vet. Clin
25,6:494-500,2008 - (mongrel dogs)
Hye Seong Ahn et al. Efficacy of an Injectable Thermosensitive Gel
on Postoperative Adhesion in Rat Model J. Korean Surg Soc.
79,239 245, 2010
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Hya Corp ENDO GEL
Is accredited in Europe (CE0297) and is at present used in clinical
studies
-- At the Dept. Obstet Gynec. Univ. Kiel, GERMANY ( n=120 )
-- At the German Medical Center, Dpt. Obstet. Gynecology, Dubai,
Healthcare City ( n= 50)
--The gel is easy to apply, through a simle applicator introduced
through the 5 mm trocar , with simple mechanical pressure.
No side effects were observed.
-- 35 patients had a second look laparoscopy within 8 weeks and
showed no adhesions on the suspected areras.
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Cross-linked sodium
hyaluronate, an anti-adhesion
barrier gel in gynecological
endoscopic surgery,
Mettler, L.epub. MITAT,2013
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Abstract
Objectives:
In the context of common adhesion prevention in laparotomic,
laparoscopic and hysteroscopic surgery this article details the effects of
a cross-linked sodium hyaluronate anti-adhesion barrier gel. The
observed adhesion score is expressed in the following threee
measurements: severity, extent and incidents of adhesions.
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Material and Methods:
From a total of 85 patients treated by laparoscopy or hysteroscopy
,where HYA CORP Endo Gel was applied, a
second look endoscopic procedure could be performed in 35 cases.
Results
Our preliminary, short evaluation of 35 patients submitted to a second
look laparoscopy or hysteroscopy revealed the beneficial effect of the
applied HYAcorp Endo Gel, showing only a minimal amount of
adhesions at the second look observation.
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Conclusion:
Cross-linked sodium hyaluronate
is highly effective in the prevention of
adhesions at laparoscopic and hysteroscopic surgery.
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Schematic presentation of genital adhesiolysis via laparoscopy
180 x 157 mm (300 x 300 DPI)
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Consequences of operative injury
254 x 190 mm (96 x 96 DPI)
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Table 1
Adhesion prophylaxis in 85 gynaecological endoscopic cases (2011
2012)
Laparoscopies n
Myoma enucleations
Endometriomas
Ovarian Cysts
Hysterectomies (TLH)
24
16
20
15
Total 75
Hysteroscopies n
Septum resections
Myoma enucleations
5
5
Total 10
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Table 2: Qualitative and quantitative composition of HYAcorp endo gel
1ml of HYAcorp endo gel contains:
Na-hyaluronate, cross-linked hylan gel 20 mg
Na-hyaluronate 10 mg
Sodium chloride 6,9 mg
Water for injection add 1 ml
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Table 3
Adhesion scores exspressed in severity extent and incidence
(0 3) after endoscopic surgery applying Hyacorp endogel in a
second look endoscopic evaluation
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Experience of using Hya Corp Endo Gel in
Gynaecology OPEN Surgery
1. Caesarian sections
2. Oncology Surgery as ovarian cervial and uterine
cancer
3. Laparotomy for large fibroids, bowel re-section and
endometrosis.
4. Paragynaecological procedures : Appendectomy,
adhesionlysis and etopic pregnancy treatment.
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Summary for the studies on Adhesesion prevention
with Hydro Gels and Hydro Flotation
The formation of postoperative adhesions is a significant
cause of morbidity and burdens healthcare systems and even
best surgical practise cannot avoid adhesion format
SprayShield

is a site-specific adhesion barrier that

polymerizes within seconds of spraying it on tissues and
protects tissues from adhesion formation while the tissues
heals, it allows immediate irrigation.
The blue colorant of the SprayShield

barrier enables the

surgeon to visualize the area of application for better cont
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Summary for the studies on Adhesesion prevention
with Hydro Gels and Hydro Flotation
An equivalent adhesion barrier is COSEAL, with no coulor for vision
The hydroflotation principle od ADEPT is very good but should best
be used in a combined approasch with PEGs or the absorbable ant-
adhesion barrier on hyaluronidase basis Hya-Corp endogel.
Hya-Corp endogel is a potent physical barrier
against the contact between adjacent tissues for at least 7 days.
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Adhesions - can we prevent or attack
them??
Yes we can by
1. careful, good surgery, preventing larger traumas, infection ,
irritation spilling and immune response
2. adhesion prevention with PEGs may be improved by adding
medications
3. The rinsing solution Adept is complimentory to PEGs and
substitute Ringers lactate to optimize a full concept of
surgical adhesion prevention
4. Hya-Corp endo gel , obtained by crosslinking special
designed hyaluronic acid , is a promising new agent and
may also be combined with ADEPT
,
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Literature of Liselotte Mettler
over 500 publications, 20 text books
1. From air insufflation to robotic endoscopic surgery: a rocky
road. Mettler L. J Minim Invasive Gynecol; 2011 May-
Jun;18(3):275-83.
the AAGL journal
2. Practical Manual for Laparoscopic and Hysteroscopic
Surgery
( Atlas and textbook with 32chapters and integrated DVDs )
Schollmeyer, Th, Mettler, L, Ruether,D. and I. Alkatout
J aypee Broth. 2012
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
UNIVERSITTSKLINIKUM
Schleswig-Holstein
Campus Kiel
KIEL SCHOOL // Zertifiziertes Ausbildungszentrum der AGE
Vielen Dank to
SICOG 2013
SKIN MD PTE LTD
&
MEDICAL REVOLUTION TECHNOLOGY
The End