adhesions occur as a result
to Adhesion Formation
De novo adhesions occur as a result of the surgical procedure
Reformed adhesions occur at the same location as previous adhesions that
were lysed or resected
Despite refinement in operative technique and the recent introduction
of adhesion-prevention products, the problem of postoperative adhesions
remains a major cause of infertility and pain. All surgeons must deal with
the potential for formation of adhesions after surgery, as well as the
sequelae of adhesions from previous surgery which may markedly increase
the difficulty of any particular surgerical case.
Post-surgical adhesions often occur following pelvic and abdominal
surgery. Data has suggested that 67% to 93% of patients will develop adhesions
following non-gynecologic abdominal surgery and 55% to 100% of patients
will develop adhesions following gynecologic surgery. These issues become
critically important from a standpoint of reproductive potential.Additionally,
adhesions may be associated with issues such as pelvic pain, abnormalities
of bowel function, and small bowel obstruction.
Several definitions of adhesions exist. De novo or new adhesions may
form at a site where none existed before but a surgical procedure was performed.
Examples include a myomectomy incision or an ovarian incision at the time
of ovarian cystectomy. De novo adhesions may also develop away from the
site of surgery,such as adhesions developing around the tubes and ovaries
at the time of a cesarean section. Adhesions may also reform following
adhesiolysis or adhesiectomy. Three general types of adhesions exist -
filmy, vascular, and cohesive. The underlying pathophysiology of all three,
however,is similar. The American Fertility Society has attempted to classify
adhesive disease according to the location and type of adhesions.
An understanding of the anatomy of the peritoneum and the response
of the peritoneum to injury is important in understanding how we might
prevent adhesion formation. The peritoneum is composed of multiple layers.
The mesothelium is the innermost layer, a layer of connective tissue
which contains the blood vessels, and a basement membrane. When the peritoneum
is injured (which is inevitable during surgery), there is an inflammatory
During the initial phase of this inflammatory response, inflammatory
mediators and histamine are released from mast cells and leukocytes.Capillaries
located within the connective tissue dilate and an increased permeability
of the capillary wall is noted. This allows leukocytes, red blood cells
and platelets to become concentrated at the site of in injury. A fibrinous
exudate is thus formed at the site of injury. Multiple factors such as
prostaglandins, lymphokines, bradykinin, serotonin, transforming growth
factor and other chemotactic agents are present within the exudated material.
At this point the fibrinous exudate may be cleared through
fibrinolysis. In order for this to occur, plasminogen must be converted
to plasmin by tissue plasminogen activator (t-PA).There is a constant balance
in the system between tissue plasminogen activator and plasminogen activator
inhibitors. Unfortunately, surgical trauma may have an inherent ability
to decrease tissue plasminogen activity while increasing plasminogen activator
inhibitors. Under normal circumstances plasmin breaks down exudated fibrin.
If this does not occur, the fibrinous exudate is converted into an organized
adhesion and fibers of collagen are deposited. Following this, blood vessels
begin to form allowing organization of the adhesion.
This process occurs over a one to seven day period of time.
In general, at seven days the quantitative development of adhesions is
complete. Qualitative changes continue over the next several months with
adhesions becoming more dense and vascularized.
below is another look of No Adhesion formed and Adhesions formed
as shown in the last bottom 2 photos above
|Caption under left upper diagram:
This is a representation of a normal peritoneum, the
transparent membrane that wraps the pelvic and abdominal organs.
|Caption under right upper diagram:
After surgical trauma, fibrous bands of collagen grow
as part of the normal healing process and form adhesions. Adhesions connect
tissues or structures that are normally seperate. Adhesions in the abdomen
or pelvic area can lead to problems such as infertility, pelvic pain, small
bowel obstructions or the need for repeat surgery.
Our efforts at adhesion reduction have thus been
an attempt to alter the previously described process. These may generally
be described as
1) minimizing peritoneal injury during surgery,
2) reducing the local and inflammatory response,
3) inhibiting the coagulation cascade and promoting
4) using barriers for separation of surfaces
at high risk for adhesion formation.
of Pelvic Conditions
Structure of the Pelvic Bones
The structural anatomy of the lower torso
can be categorized into four specific and distinct segments:
1. The pelvis,
2. The sacrum,
3. The lumbosacral junction,
4. The lumbar spine.
The pelvic joints include the pubic symphysis
joint (where the two pubic bones meet) and the two sacroiliac joints, (where
the pelvic bones join the sacrum). These three joints work together, promoting
a "mobile stability" for standing, balance, moving, walking and stair climbing.
Because of the way that these joints function, the repetitive movements
that affect them, and the translation of forces that go up the legs and
through these joints, biomechanical dysfunctions are very common at the
The Bones and Joints of the Pelvis
Clinically, we see pelvic joint dysfunctions
as structural and postural imbalances. The pelvis may appear higher on
one side as compared to the other side. Due to the pelvic imbalance, one
leg may appear slightly longer than the other.
Chronic pelvic imbalances typically create far
reaching mechanical and soft tissue dysfunction within the body systems.
Because the pelvis is the foundation and base of support for the back,
spinal column, chest, shoulder girdles, neck and head, asymmetry in the
pelvis often gets relayed to the skull due to postural adaptations. These
compensations may occur in the lumbar, thoracic and cervical spines due
to the pelvic imbalances.
The pelvis is also the transition point of weight
between the legs and the upper
body. Anatomically, a single column of central weight (the spinal column)
must be structurally transferred into two columns (the hips to the lower
legs,) or the other way around.
This occurs at the lumbosacral region. Nature designed this area to be
highly stable to promote the transfer of weight from one column into two,
or two into one. This area is also the body’s center of gravity. If the
pelvis is not stable when a motion occurs, you have to compensate above
or below. This important and vital area is subject to ongoing structural
stresses with every step we take. Despite the tremendous structural load
it carries, the pelvis also contains and supports some of the most delicate
and vulnerable structures in our body, our abdominal and pelvic organs.
The Pelvic Organs
Due to the anatomy and function of
the female urogenital system, the female pelvis is much more open and
vulnerable to the outside environment than the male pelvis. The female
pelvis is also shorter and wider than the male pelvis to allow for childbirth.
These structural differences make a woman’s pelvis subject to a significantly
higher incidence of infection, trauma, pain and dysfunction.
Endometriosis, sexually transmitted and pelvic
inflammatory diseases, vaginal , bladder and yeast infections can cause
abdominal, pelvic or low back pain or dysfunction, including infertility.
Due to tiny adhesions which form as part of the healing process, these
infections and inflammatory processes may cause symptoms long after the
inflammation has passed.
Adhesions may cause pain or infertility
Many women have at least one or more
abdominal or pelvic surgeries. There is no doubt that surgery is often
necessary, and may be a life saving procedure. But even the most skilled
surgeon cannot prevent the formation of adhesions after some surgeries.
a recent study in the British Journal of Surgery, 55% to 100% of patients
will develop adhesions following gynecologic surgery. Surgeries such
as episiotomy, C-section, abortion, hysterectomy, D. and C., and even lysis
(removal) of adhesions may cause additional adhesions to form.
Magnitude of the Problem of Adhesions
The Magnitude of the Problem of Adhesions
The rate of adhesion formation rate after surgery
is surprising given the relative lack of knowledge about ADHESIONS among
doctors and patients alike. From autopsies on victims of traffic
accidents, Weibel and Majno (1973) found that 67% of patients who had undergone
surgery had adhesions. This number increased to 81% and 93% for patients
with major and multiple procedures respectively. Similarly, Menzies
and Ellis (1990) found that 93% of patients who had undergone at least
one previous abdominal operation had adhesions, compared with only 10.4%
of patients who had
never had a previous abdominal operation.
Furthermore, 1% of all laparotomies developed obstruction due to adhesions
within one year of surgery with 3% leading to obstruction at some time
after surgery. Of all cases of small bowel obstruction, 60-70% of
cases involve adhesions (Ellis, 1997).
Lastly, following surgical treatment of adhesions
causing intestinal obstruction, obstruction due to adhesion reformation
occurred in 11 to 21% of cases (Menzies, 1993).
Between 55% and 96% of patients undergoing
pelvic reconstructive surgery will form adhesions.
Michael P. Diamond, MD
Professor, Department of Obstetrics &
Gynecology, Wayne State University, USA
Director, Division of Reproductive Endocrinology
Diaa M. EI-Mowafi, MD
Associate Professor, Department of Obstetrics
& Gynecology, Benha Faculty of Medicine, Egypt
Researcher & Educator, Wayne State University,
Fellow, Geneva University, Switzerland
Pelvic adhesions observed in gynecologic patients are a major contributing
factor to infertility, pelvic pain and/or intestinal obstruction. Such
adhesions may be the sequelae to inflammatory processes, endometriosis,
and prior surgical intervention. The latter will be the main topic of this
It has been recognized that pelvic adhesions occur in 55-95% of women
following a laparotomy.1
This occurs in clinical trials in spite of different meticulous methods
used to achieve this goal, including microsurgical technique, operative
laparoscopy, the use of carbon dioxide laser and the use of medical and
surgical adjuvants.2 This
chapter explores the pathophysiology of adhesion formation and the different
methods of its prevention or reduction. These different methods include:
different ways to get into the abdomen (i.e. via laparotomy or laparoscopy),
the variable surgical methods used either during the initial pelvic surgery
or adhesiolysis which include macrosurgery, microsurgery, laser surgery
and endoscopic surgery, and lastly, the different medical and/or surgical
adjuvants used to prevent adhesion formation.
Pathophysiology of Adhesion Development
Adhesion development represents a disruption in the normal physiological
process of peritoneal healing, although it is probably incorrect to call
it abnormal healing since adhesion development can be thought of teleologically
as a way for the body to resupply oxygen and nutrients to devascularized
tissues. Following peritoneal injury, the process of healing without adhesions
is initiated by release of histamine and vasoactive kinins causing an increase
in capillary permeability with subsequent outpouring of serosanguinous
fluid within three hours. This proteinacious fluid will coagulate, producing
fibrinous bands between the denuded areas.3
variety of inflammatory cells, including monocytes, plasma cells, polymorphonuclear
cells, and histiocytes migrate to these fibrinous bands. Importantly,
the fibrinolytic system is triggered to lyse these bands, usually within
72 hours. The denuded area of peritoneum is then reepithelized,
probably within three to five days, with healing completed within 3 to
4 weeks. In contrast to skin which reepithelizes from the edges in, reepithelization
of the peritonea injury begins with, mesothelial migration from underlying
primitive cells to line the denuded area into the peritoneal supportive
matrix. If a disturbance in this equilibrium between fibrin deposition
and fibrinolytic activity occurs, the fibrinous strands will persist, and
will subsequently be infiltrated by proliferating fibroblasts, and later,
new angiogenesis will take place and if tissue ischemia exists, thus an
adhesion is created.4
In fact, the definite etiology of pelvic adhesion formation is not
clearly well known, but the following risk factors have been incriminated
in this process:
Tissue hypoxia or ischemia.
Rough manipulations of tissues during surgery.
Presence of reactive foreign body.
Presence of intraperitoneal blood.
Dissection of prior adhesions.
Ischemia of the tissues may result from excessive or rough tissue handling,
ligating, suturing, crushing, cauterizing or stripping of the peritoneum.
These may cause adhesion formation via inhibition of the fibrinolytic activity
(which resides in peritoneal tissue) and stimulation of angiogenesis from
a non-ischemic area to that devoid of its adequate blood supply. In addition,
desiccation of the peritoneal tissue during prolonged surgical procedures
may result in mesothelial cell desquamation with a resultant raw basement
membrane and fibrin deposition.5
The common reactive foreign bodies that may be introduced into the
field during surgery include: sutures, talc powder from surgical gloves,
lint from drapes, cans, gowns, masks or laparotomy pads. Such foreign bodies
lead to niduses excessive formation of the fibrin mass, which may result
in adhesion formation. Interestingly, however, adhesions are less likely
to develop in the presence of foreign body without coincidental peritoneal
The presence of intraperitoneal blood has been proposed to cause adhesions
formation, although its actual role is not well understood.5
In general, intraperitoneal blood usually does not cause adhesion formation,
except in the presence of tissue ischemia.7
It was a common concept that the mechanism of de novo adhesions formation
and reformation after adhesiolysis is the same, although there is no experimental
data supporting this. Nevertheless, in both experimental and clinical investigations
the probability for adhesion reformation was greater than its de novo formation.1
This may be attributed to the higher degree of tissue ischemia in the previously
damaged tissues than the native one.
Staging of Adhesions
Staging or classification of any medical or surgical disorder is the
cornerstone to reach a univocal understanding facilitates communication
among physicians and investigators, give a true judgment on the different
modalities of treatment and clarify the expected prognosis for every individual
case. Going into a medical or surgical disorder without staging or classification
is like looking for luggage without an identification tag at Heathrow Airport.
In 1982, Hulka8 published
a prognostic classification after five years of surgery for infertile patients
in his institute. His classification was based upon 2 main factors; the
extent of ovarian involvement and the nature of adhesions, whether filmy
or dense. The poorest prognoses for achieving a spontaneous conception
were in those patients with dense adhesions covering more than 50% of the
ovarian surface visible at laparoscopy.
The American Fertility Society (AFS) classification of adnexal adhesions
(1985) had a great acceptability and became a universal one for many years.
Recently, the Adhesion Scoring Group (1994)1
published their more comprehensive adhesion scoring system based on evaluation
of 23 individual locations in the abdominal cavity for severity (0, none;
1, filmy, avascular; 2, dense and/or vascular; 3, cohesive) and extent
of total area or length (0, none; 1£ 25%; 2, 26-50%; 3, >50%;4).
The Adhesion Scoring Group reported that although the AFS adhesion
scoring method generated significant agreement between pairs of surgeons,
the use of the more comprehensive adhesion scoring method specifically
demonstrating locations, severity, and the extent of adhesions produces
a marked increase in reproducibility between surgeon pairs in scoring pelvic
Unfortunately, none of these systems have been validated with clinical
outcomes, and it is unlikely that they ever will be. The latter is because
at second-look to score adhesions, additional surgical intervention is
usually conducted; thus, clinical outcomes reflect the results of the second
look procedure as opposed to the status of the pelvis at the beginning
of the procedure.
As the previous classifications need the usage of an invasive procedure
(usually laparoscopy) to achieve it, ultrasonography as a non-invasive
tool was used recently to attempt to classify the pelvic adhesions.4
Surgery or Assisted Reproductive Techniques?
For many decades, surgical adhesiolysis was the only realistic option
for an infertile patient with pelvic adhesions. After the birth of the
first "test tube" baby, Louise Lesley Brown, in 1978 in England, a revolution
in the use of assisted reproductive techniques (ART) took place. These
in vitro fertilization and embryo transfer (IVF-ET), gamete intrafallopian
transfer (GIFT) and zygote intrafallopian transfer (ZIFT). Microinjection
(micro-manipulation), which entails mechanical transfer of sperm into the
oocyte by a special micropipette is the most recently introduced assisted
reproductive technique if there is an additional contributing factor for
infertility such as severe oligospermia or athenospermia, or inability
of sperm to penetrate the oocyte due to immunologidal factors. The main
procedure for microinjection is intracytoplasmic sperm injection (ICSI),
where the micropipette carrying the sperm is introduced through the zona
pellucida into the oocyte cytoplasm and one sperm deposited. Now, the question
is, which is more beneficial to the infertile female with pelvic adhesions;
surgery or ART? Reported pregnancy rates after surgical treatment of pelvic
adhesions vary from 25% to 75%. Rock et al.,10
reported normal pregnancy rates after surgery on severe, moderate and mild
distal tubal obstruction to be 5%, 17% and 80% respectively, while the
ectopic pregnancy rates were 0%, 13% and 6% respectively. The 17% rate
of normal pregnancy reported after surgical treatment of moderate disease
is comparable to the clinical pregnancy rate of 16% per retrieval for IVF-ET
which was reported consistently over four years by the United States National
IVF-ET registry.11 However,
the 13% rate of ectopic pregnancy seen after surgical repair of moderate
disease is nearly three times the approximately 5% rate expected after
Before choosing between surgery or ART, one must consider the severity
of adhesions (the more extensive and dense, the poorer the prognosis of
surgery)13, the patient's
age, previous reproductive surgery, coexistent infertility factors as poor
semenogram, suspected cervical or immunological cause and last, but not
least, the financial constraints.
If the surgical approach is the wisest decision, the rational now is
to reduce adhesion formation following both the primary reproductive surgery
and/or adhesiolysis. This rationale passes through the following three
I. Getting into the abdomen.
II. Surgery inside the abdomen.
III. Adjuvants for adhesion reduction.
Getting into the abdomen:
Laparoscopy versus Laparotomy
The era of operative laparoscopy started in the 1980s and expanded
to involve most of the previous traditional pelvic surgery. The advantages
of endoscopic surgery are claimed to be reduction of hospital stay, postoperative
pain, length of abdominal incision, and expense. One of the claims is the
reduction of subsequent postoperative adhesion formation. This view is
supported in theory by the concepts of lack of retractors and packs usage
at laparoscopy, maintaining a closed abdomen with presumed reduction in
peritoneal drying, less likelihood of introduction of foreign bodies, decreased
possibility of blind dissection of adhesions during abdominal exploration
and less tissue damage at the abdominal wall incision(s) compared to that
of laparotomy. Luciano and co-worker14
demonstrated no intra-abdominal adhesions in rabbits with the lesions created
laparoscopically, whereas those lesions created at laparotomy were consistently
followed by adhesion formation. Furthermore, the investigators then assigned
those animals with adhesions to adhesiolysis at laparotomy or laparoscopy
and demonstrated greater reduction in adhesion reformation following laparoscopic
adhesiolysis. In their study, Nezhat and co-worker15
no de novo adhesion formation at non-operated sites at a second look laparoscopy
done 4-8 months after laser laparoscopy for the treatment of endometriosis
associated infertility in 157 patients. An overall 60-79% reduction in
adhesions in patients undergoing adhesiolysis was observed. Diamond and
in a multicenter study a high (97%) incidence of adhesion reformation seen
at early (90 days) second-look laparoscopy following laparoscopic adhesiolysis.
Moreover, adhesion reformation occurred regardless of the consistency or
vascularity of the initial adhesion. This incidence is consistent with
that previously reported following adhesiolysis at laparotomy, therefore
they concluded that adhesion reformation would not be able to be eliminated
by utilization of endoscopic surgery per se. Their report also pointed
to a 12% of patients who developed de novo adhesions.
At this time, it seems that there is no clear and convincing evidence
that laparoscopic adhesiolysis in humans is superior to microsurgical lysis
of adhesions at laparotomy in terms of adhesion reformation or subsequent
Surgery inside the Abdomen
The use of microsurgery in reproductive pelvic surgery was first described
by Swolin in 1967.17
The term microsurgery basically implies the use of magnification to allow
close visualization, differentiation between healthy and pathologic tissues,
handling the small caliber microsurgical instruments, and use of fine sutures.
The fine sutures should be non-reactive, such as Vicryl, Dexon, or non-absorbable.
The other main principles of microsurgery have included: minimization of
tissue handling, prevention of tissue desiccation, avoidance of introduction
of foreign bodies such as talc into the operative field, precise reapproximation
of tissue planes and meticulous hemostatis.18
probably of greater controversy among these dictums is the benefit of precise
approximation of tissue planes. Tulandi and his colleagues19
reported that leaving the anterior abdominal wall peritoneum unsutured
after laparotomy results in less postoperative adhesions than its closure.
However, they used chromic suture for closure; if a less reactive suture
had been used, more difference might be noticed. Moreover, several studies
recently suggested that ovarian bisection in animals results in fewer adhesions
when the ovary is left open rather than closed. 20,21
In general, the use of microsurgical technique for adhesiolysis has
improved the pregnancy outcome. It is difficult to interpret the results
of the reports in the literature because of the variation in adhesion extent,
consistency, and vascularity in addition to the personal skill variation.
However, the following table shows a comparison between the results of
use of macrosurgery versus microsurgery for adhesiolysis.
Table (1) Comparison between the results of macrosurgery versus microsurgery
Total No. of Patient
|Wallach & co-workers 22
|O’Brien & co-workers24
|Betz & co-workers25
|Caspi & co-workers13
|Donnex & Casanas-Roux28
|Frantzen & Schlosser30
Laser Endoscopic Surgery:
Different types of laser now used in the reproductive pelvic surgery
include argon, potassium-titanyl-phosphate (KTP-532), neodymium:yttrium-aluminum-garnet
(Nd:YAG); but the most frequently used to date is the carbon dioxide, employed
for its superficial site of action and variable spot size. It has been
postulated that laser surgery will decrease dramatically the incidence
of adhesion formation and reformation by virtue of making precise incisions,
minimization of tissue handling, maintenance of meticulous hemostasis and
reduction in operative time. However, in rabbits and rats, no reduction
in post-operative adhesion was seen when the CO2 laser was compared with
fine needle cautery.31,32
In a multicenter prospective study, an early
(within 12 weeks) second-look laparoscopy was performed by Diamond and
his colleagues33 to
assess tubal patency and adhesion formation after intra-abdominal laser
surgery. Procedures performed included neosalpingostomy, fimbrioplasty,
lysis of adhesions, vaporization of endometriosis, and ovarian wedge resection.
The results were compared with those of another multicenter prospective
study that utilized non-laser reconstructive pelvic surgery. Use of CO2
laser was found to result in a greater tubal patency rate and adhesions
were reduced from initial presentation at most sites. However, non-laser
infertility surgery appeared to have equal or greater efficacy in the prevention
of adhesion formation. It was concluded that the CO2 laser does not appear
to be a panacea for the treatment of tuboperitoneal causes of infertility.
11 patients at second-look laparoscopy 12 to 21 days following laser laparoscopic
adhesiolysis. No intraoperative agents were used for adhesion prevention.
Fifteen sites were evaluated for adhesions. All patients had adhesion reformation
in at least one site. Fifty-six percent of available sites had adhesions
at second-look laparoscopy, which was not a significant change from the
60% of sites with adhesions of initial laparoscopy. De novo adhesions formed
in seven of the patients at 23% of available sites.
utilized early second-look laparoscopy, done 6 to 12 weeks postoperatively,
to evaluate recurrent adhesion formation following laser ovarian wedge
resection. Forty-nine ovaries in 25 consecutive infertile patients underwent
laser surgery for deep endometriosis or polycystic ovarian disease, refractory
to medical treatment. On second-look laparoscopy, 36.7% of the ovaries
had recurring adhesions; 83.3% of these adhesions were mild and filmy,
and 16.7% were moderate and dense. Additionally, 2 ovaries that had mild
and filmy adhesions lysed at 6 weeks during the second-look laparoscopy,
have been found to have no recurrent adhesions when viewed one year later
postoperatively. The actual pregnancy rate in this study is 60%, with 15
of the 25 patients conceiving at least once and two patients conceiving
twice. The majority of pregnancies occurred within the first six months
postoperatively, with the longest initial pregnancy occurring 22 months
postoperatively. The author concluded that laser ovarian surgery, coupled
with early second-look laparoscopy, appears efficacious in minimizing adhesion
reformation and seems to have little adverse effect on subsequent conception.
stated that CO2 laser remains the most precise laser, especially in the
ultrapulse mode, for the division of adhesions and the accurate and safe
vaporization of deposits of endometriosis. The neodymium:YAG laser, because
of its greater depth of penetration, is more suited to hysteroscopic surgery.
Carbon dioxide laser energy is strongly absorbed by the water molecule
and is rendered ineffective in the presence of blood, so the visible light
argon and KTP-532, are more suitable for the
treatment of ovarian endometriomas and ectopic pregnancies. The author
concluded that the main advantage of the various lasers is that they allow
fertility surgeons to perform operative surgery by the minimally invasive
approach of laparoscopy rather laparotomy.
To summarize these and other studies appearing
in the literature, it appears that lasers are useful for the performance
of gynecological procedures when utilized by surgeons experienced in their
use. However, it does not appear that use of a laser per se reduces postoperative
adhesions or the complications they cause as compared to other surgical
modalities. Furthermore, it appears that the use of lasers is generally
decreasing, as surgeons become more experienced with alternative means
of incising/excising tissue and in establishing hemostasis
VALUE OF SECOND-LOOK LAPAROSCOPY (SLL)
The principle of SSL was first introduced by
Swolin to evaluate the result of some surgical procedures.1
principle soon became a routine used by many gynecological surgeons and
investigators allowing a chance to perform adhesiolysis for the de novo
or recurrent adhesions encountered during SLL. This is assumed to give
the infertile patient a better opportunity to get pregnant. Trimbos-Kemper
to further "third-look laparoscopy" in patients who had undergone an early
second-look procedure with adhesiolysis at that time. They reported that
more than half of the adhesions that were separated at the second-look
laparoscopic procedure did not recur. The same was shown by Jansen38,
reported that second-look laparoscopy resulted in a significant reduction
in adhesions at the time of a "third-look laparoscopy". The next logical
question is: does the second-look laparoscopy provide benefit in terms
of increasing the incidence of intrauterine pregnancies and/or decreasing
that of ectopic pregnancy? Trimbos-Kemper37
a reduction in the incidence of ectopic pregnancy in women who had undergone
SLL, although the intrauterine pregnancy rate was unchanged. Surry and
a 52.1% intrauterine pregnancy in 31 patients who had undergone early SLL
after reconstructive pelvic surgery. Unfortunately, none of these studies
have been properly designed to provide a definitive answer to the value
of second-look laparoscopy.
Other potential advantages of second-look laparoscopy
include the ability of the surgeon to assess the efficacy of surgical techniques
or adjuvants, as well as to provide the patient a reasonable assessment
of likely prognosis. If the patient is among the approximately ten percent
of subjects in whom adhesions worsen, that patient may benefit from early
referral to ART as opposed to protracted lengths of time spent trying to
conceive against very long odds.
What is the reasonable time for SLL? Even now,
it is still a matter of personal opinion and controversy, varying from
few days 37,38,40 to
three years41 postoperatively.
Swolin's opinion encouraged 6 weeks postoperatively as an optimum period
for SLL42. Some
surgeons feel that adhesiolysis performed via SLL carried out less than
2 weeks after the initial surgery is associated with increased bleeding
from granulation tissue at adhesion sites; others prefer this interval
because it is before patients have fully recuperated from their initial
surgery and they anecdotally feel adhesions are easier to separate at this
early time. Clinical studies, however, have not been able to identify differences
in the frequency or severity of adhesions from intervals of 1-2 weeks to
3-4 months between the two procedures. Importantly, this suggests that
if adhesions are going to develop postoperatively as a consequence of the
surgical procedure that they will do so during the initial week after surgery.1
On the other hand, bleeding will also be considerable if the procedure
is done more than 12 weeks after surgery as the adhesions become more dense
Adjuvants for Adhesion Reduction
Adhesion formation and reformation are still
an unavoidable event in reproductive pelvic surgery in spite of the variable
skills in microsurgery, endoscopic or laser surgery. This fact necessitates
the search for an adjuvant(s) that can be used in the perioperative period.
The field of these adjuvants becomes large enough to require a classification.
Table (2): Classes of adhesion-reduction adjuvants
and their proposed mechanism of action
I. Fibrinolytic agents (fibrinolysis,
stimulation of plasminogen activators)
II. Anticoagulants (prevention
of clot and fibrin formation)
III. Anti-inflammatory Agents (reduce
vascular permeability, reduce histamine release and, stabilize lysozomes)
Nonsteroidal anti-inflammatory agents
Calcium channel blockers
VI. Antibiotics (prevent infection)
V. Mechanical Separation (surface
A. Intra-abdominal Instillates:
Chelated hyaluronic acid
Oxidized regenerated cellulose
Modified from Diamond MP, DeCherney AH: Pathogenesis
of adhesion formation/reformation: Application to reproductive pelvic surgery.
Microsurgery 1987: 8: 103 and Diamond MP, Hershlag A: Adhesion formation/reformation:
in Treatment of postsurgical Adhesions, Wiley-Liss, Inc. 1990: 23-33.
Fibrinolytic agents act directly by reducing
the fibrinous mass and indirectly by stimulating plasminogen activator
Plasminogen activator is a serine protease that
converts plasminogen into plasmin, which causes fibrin degradation. Recombinant
tissue plasminogen activator (rtPA), delivered locally, was investigated
by Vipond and colleagues44
in rats and found to be successive in reduction of adhesion formation significantly.
It was even superior to carboxymethylcellulose (CMC) gel used in another
group in the same study. CMC is another chemical component widely investigated
for prevention of adhesions. Again, LeGrand and co-workers45
reported in their study on a rabbit model that imidazole, a thromboxane
synthetase inhibitor, showed significant efficacy in prevention of adhesion
formation to the uterine horn. They also found that Ridagrel, an inhibitor
of thromboxane synthetase as well as a thromboxane A2 receptor blocker,
also showed significant efficacy in reducing peritoneal adhesion severity.
These results were contradictory to that of two other studies. The first
was carried out by Gehlbach and others on rabbits46.
They concluded that the combination of intraperitoneal rtPA and carboxymethylcellulose
(CMC), did not reduce postsurgical adhesion reformation, and was associated
with hemorrhagic complications. The second study was carried out by Bothin47
on rats and reported the rtPA and oxidized regenerated cellulose (ORC),
which is an exogenous barrier, were unable to decrease adhesion formation.
Nevertheless, rtPA mitigated the adhesion-increasing effect of ORC. Another
worse drawback was reported by Evans and colleagues48
as they noticed that the levels of rtPA reguired to alter or prevent intra-abdominal
adhesion formation also produce a significant impairment of the early phase
of wound healing as measured by the wound content of hydroxyproline. Prior
investigations have shown a strong correlation between wound-bursting strength
and hyroxyproline content. The use of fibrinolytic agents in humans awaits
Heparin is the most widely investigated anticoagulant used for prevention
of adhesions. Its mechanism of action is probably through one of the following:
first, heparin may interact in the clouding cascade by a combination with
antithrombin III.49 Second,
heparin directly stimulates the activity of plasminogen activators, thereby
promoting breakdown of fibrin clots once they form.50
Lastly, heparin may act by binding to fibroblast growth factor (FGF) leading
to considerable improvement in healing of cutaneous wounds.51
Heparin has been added to peritoneal irrigants with concentrations around
5U/ml.52 In animal studies,
this route of administration proved its efficacy.53,54
In rat uterine horn model, Sahin and Saglam55
added the low molecular weight heparin to the sodium carboxymethylcellulose
solution instilled at laparotomy. They reported that this combination is
highly effective in reducing postoperative adhesions in this animal model.
Heparin has also been added to the local mechanical barriers to enhance
its anti-adhesive benefit. Tayyar and co-worker56
added heparin to the amniotic membrane used to cover experimentally injured
rabbit uterine horns. They showed that this combination was effective in
reducing adhesion formation. In a rabbit uterine horn model study, Diamond
and co-workers57 reported
that heparin delivery by intraperitoneal lavage, intravenous injection,
or intra-abdominal instillation failed to reduce adhesion formation. Similarly,
heparin delivery with other intraperitoneal instillates as carboxymethylcellulose
or 32% Dextran 70 failed to demonstrate efficacy. In their study, a significant
reduction in adhesion formation was only observed with the combination
of Interceed (TC7) and heparin where Interceed was utilized as a carrier
to deliver heparin to traumatized surfaces. In another study, the same
group of investigators reported that combination of the Interceed plus
heparin in a dose of 500 and 1000 USP units per rabbit uterine horn resulted
in a significant reduction of the adhesion reformation scores.58
This improvement in efficacy was not able to be demonstrated in a clinical
trial done by Reid and co-workers59
where, after ovarian cystectomy and/or ovariolysis at laparotomy, one ovary
was wrapped in Interceed TC7, and the contralateral ovary was wrapped in
Interceed TC7 saturated with a heparin solution (1,000 U/ml). They noted
that addition of heparin did not enhance significantly the adhesion-reducing
capacity of the Interceed TC7 barrier when applied to ovarian surfaces.
However, it should be noted that the efficacy of Interceed alone in
the trial exceeded its efficacy in another recent clinical trials.60
This group of agents was used to reduce the initial
inflammatory response to tissue injury and hence, subsequent adhesion formation.
This goal is probably achieved through the capability of these agents to
reduce vascular permeability, inhibit synthesis and release of histamines
and/or stabilize lysosomes. Anti-inflammatory agents that have been investigated
included corticosteroids, nonsteroidal agents, progesterone and progestogens,
antihistaminics and calcium channel blockers.
Corticosteroids have been shown to decrease adhesion
formation in small animals.61,62
of the large dosages required, the high risk of immunosuppression, infection
and wound disruption have been noted.63
Corticosteroids were probably used on a large scale in clinical practice
following Swolin's report that intraperitoneal hydrocortisone reduced adhesion
formation as proved at SLL.64
But it is of importance to mention that all patients who received adjuvant
for adhesion reduction were operated by Swolin, whereas those who did not
receive corticosteroids had other primary surgeons. In fact, most of the
animal studies failed to prove any reduction in adhesion formation with
diZerega and Hodgen65
found perioperative dexamethasone and promethazine to be ineffective in
preventing adhesion formation after trauma to the fallopian tube. Seitz
investigated adhesion reformation after adhesiolysis in monkeys. Normal
saline, low molecular weight dextran and dexamethasone/promethazine are
three different adjuvant therapies given for separate groups. Adhesion
reformation was similar in each of the three groups. The other few clinical
trials for corticosteroid usage failed to prove its efficacy in reduction
of adhesion formation.67
Nonsteroidal anti-inflammatory drugs (NSAIDs)are
acting through several postulated mechanisms. NSAIDs have an anti-prostaglandins
effect, thereby blocking the adhesiogenic action of prostaglandins instillated
have also been shown to inhibit platelets’ aggregation, leucocyte migration
and phagocytosis, and lysosome release.5Tolmetin,
an NSAID was presumed to enhance macrophage function, and hence, allow
rapid phagocytosis of tissue debris or fibrin.69
and ibuprofen have also been shown to increase fibrinolysis through decreasing
the secretion of plasminogen inhibitors resulting in enhanced plasmin production.70,71
Most of the animal studies showed the effectiveness of NSAIDs in prevention
of adhesions. Perioperative administration of oxyphenbutazone,72
and interaperitoneal instillation of indomethacin73
have been reported to reduce postoperative adhesion formation in rats and
monkeys. In a recent study45,
a rabbit uterine horn adhesion model was used to directly compare several
commonly used NSAIDs of different chemical classes in a single animal study
to evaluate their ability to prevent adhesion formation, Tolmetin, ibuprofen,
aspirin and indomethacin all showed significant and comparable efficacy.
These results support the view that there is a common mechanism through
which NSAIDs act to prevent adhesions. In spite of that, other studies
failed to prove any beneficial effect of intramuscular or intraperitoneal
administration of ibuprofen in reduction of peritoneal adhesions in rat
and rabbit models.73,74
Unfortunately, no clinical trials with NSAIDs have been published up until
now, although several have been conducted.
Antihistamines, such as promethazine, inhibit
the inflammatory response, stabilize lysosomal membranes and inhibit fibroblast
proliferation. The use of antihistamines to prevent adhesions was in conjunction
with corticosteroids and has not been shown to be effective in human studies.75
Progesterone was investigated for reduction
of postoperative adhesions after the initial observation that adhesions
were less after ovarian wedge resection if that ovary was containing an
active corpus luteum at time of operation.76
Actually, the previous laboratory studies have elicited the anti-inflammatory
and immunosuppressive effects of the progesterone. It was also shown that
progesterone inhibits leukocyte migration77,
and T-cell activation78,
and reduces humoral antibody production. In addition, progesterone was
found to decrease vascular permeability and the resulting volume of transudate
Maurer and Bonaventura81
reported a decrease in adhesion formation if progesterone has been given
by interaperitoneal and intramuscular route. Other studies were contradictory,
finding an increase in adhesion development after intraperitoneal instillation
In addition, intraperitoneal and intramuscular medroxyprogesterone acetate
(MPA) has also resulted in an increase in postoperative adhesion formation82,84despite
a significant reduction in antibody titers to peritoneum and myometrium.84
This concept was present until Montanino-Oliva85
and others published their recent study showing that preoperative IM administration
of 15mg MPA into a rat model results in the most significant reduction
of postoperative adhesion formation, even when it has been compared to
leuprolide acetate and Ringer's lactate. They postulated that the action
of MPA might be mediated by the induction of both a progestational and
a hypoestrogenic milieu.
Calcium channel blockers have been shown
to inhibit the release of vasoactive inflammatory mediators such as histamine
and prostaglandins E and F.86
Tjssue ischemia is reduced as well by calcium antagonists.87
In addition, they have been demonstrated to inhibit platelet aggregation88,
protect against granulocyte-mediated tissue injury89,
and inhibit fibroblast migration into fibrin matrices.90
In a hamster animal model, Steinleitner and co-workers91
have demonstrated a reduction in pelvic adhesions with the use of subcutaneous
verapamil, nifedipine, and diltiazam. Continuous intraperitoneal verapamil
instillation was as effective as subcutaneous administration in the reduction
of primary adhesion formation92,
as well as adhesion reformation after lysis of peritoneal adhesions.93
These findings were unable to be confirmed in an animal study (Diamond
and Linsky, Unpublished data).
Colchicine, which is known to inhibit
histamine secretion, mitotic activity, and collagen synthesis and secretion,
has been shown to decrease adhesion formation in two studies using a rat
no further studies have been carried out in this field.
The rationale behind the use of antibiotics is
prophylaxis against infection, and hence the inflammatory response, that
leads to adhesion development. Systemic broad-spectrum antibiotics, particularly
cephalosporins, were widely used in the past. Nowadays, tetracyclines are
commonly used to protect from chlamydia, a potentially infectious organism
in the female genital tract.96
Unfortunately, there is no sufficient published
data from animal or human studies supporting this practice. In contrast,
intraperitoneal irrigation with antibiotic-containing solutions has been
demonstrated to increase peritoneal adhesion formation in rat model.
Mechanical separation of peritoneal surfaces
of the pelvic organs during the early days of the healing process postoperatively
was a practical way to prevent postoperative adhesions. This separation
may be accomplished by intra-abdominal instillates and barriers whether
endogenous tissue or exogenous material.
Crystalloid solutions were the most commonly
used instillate put into the abdominal cavity after completion of the surgical
procedure. In addition to its mechanical action in separation of the raw
peritoneal surfaces, crystalloid solutions dilute fibrin and fibrinous
exudate released from the traumatised surfaces.12
Unfortunately, crystalloid solutions are absorbed
from the peritoneal cavity at an estimated rate of 35 ml/hr. Thus a volume
of 500 ml will be absorbed within about 14 hours and 5 liters of crystalloid
solution are needed to cover the first six days postoperatively. The process
of peritoneal repair, fibrin deposition, and adhesion formation extends
quite beyond the time during which a reasonable volume of crystalloid persists.
The other drawback is the possible increased risk of infection with instillation
of such a large volume of fluid into the peritoneal cavity.3
In an attempt to prolong the period of instillate
persistence inside the peritoneal cavity, more viscous solutions have been
tried in both experimental and clinical studies. A 32% dextran-70 solution
(Hyskon) was among the most commonly used viscous solutions. Usually 200
ml of it is instilled into the posterior cul-de-sac at completion of the
surgery. Hyskon acts as a siliconizing agent, coating raw surfaces. As
an osmotic agent, it results in hyrdroflotation of the pelvic viscera,
and additionally it stimulates plasminogen activators.52
Hyskon was investigated in four large clinical trials; the first initial
two reports demonstrated a significant reduction in postoperative adhesions.99,100
The subsequent two studies failed to detect a beneficial effect to Hyskon.101,102
Complications from its use in humans have been reported, including anaphylaxis,
pleural effusion, vulvar edema, transient liver function abnormalities,
wound separation, disseminated intravascular coagulation, and abdominal
bloating after its instillation.3
Carboxymethylcellulose (CMC) is a high
molecular weight polysaccharide that acts as an adjuvant for prevention
of adhesion by coating the intraperitoneal surfaces and creating hydroflotation
of intra-abdominal structures. Using the rabbit uterine horn model, Diamond
and co-workers found that intraperitoneal instillation of CMC significantly
reduced postoperative adhesion formation and reformation.103,104
Yaacobi and colleagues105
reported that tissue coating with CMC prior to cecal abrasion in rat significantly
reduced the formation of postoperative adhesion while coating following
cecal abrasion failed to inhibit adhesion formation. A novel CMC sponge
has been developed for prevention of surgical wound adhesions. It has been
investigated by Ryan and Sax106
by performing by performing cecal denudation in rats. They concluded that
CMC sponge was more effective than Interceed in preventing postoperative
adhesions. Its action was not due to inhibition of cytokine transforming
growth factor beta (TGF-beta) expression or macrophage-derived fibrogenic
Hyaluronic acid is a glycosaminoglyucan
that under aqueous conditions forms a viscous solution. In rat studies,
instillation of hyaluronic acid before cecal abrasion reduced adhesion
while coating serosa surfaces after tissue injury was ineffective.108
Grainger and others109
used the hyaluronic acid polymers at three different molecular weights
and in form of a polymer slab to prevent adhesions in a rabbit animal model.
None of the formulations of hyaluronic acid solutions resulted in a reduction
of ovarian adhesions. Only the polymer slab significantly reduced adhesion
formation. In a recent study110,
a modified hyaluronate-carboxymethylcellulose gel was effective for reduction
of adhesion formation in rat and rabbit models after surgery in the abdominal
cavity. Treatment with this bioabsorbable gel increased the number of animals
without any adhesions by 70% in a rat cecal abrasion model and by >70%
in a rabbit sidewall defect bowel abrasion model compared with non-treatment
Poloxamers are groups of surfactants characterized
by their ability to convert from a liquid state at room temperature to
a gel form at temperatures higher than 25oC. If recooled, the polymer returns
to its liquid state and conversion can be repeated. Poloxamer 407 of Flowgel
is derived from a 4000 Kd hydrophobe and is composed of polyoxythylene
and polyoxypropylene. Rice and colleagues111
used 0.5-1.5 ml of this poloxamer solution to cover uterine and sidewall
defects in rabbit models. They noted a significant reduction in primary
postsurgical adhesions; 95% of the control side had adhesions compared
to 40% of the treated side.
Endogenous barriers as human amniotic membrane
graft was tried to cover the traumatized surfaces for prevention of adhesions.
In a rabbit-uterine horn model, Arora and co-workers112
showed that amniotic membrane graft failed to have the preventive effect
on adhesion formation it is claimed to possess. Even worse amniotic membrane
graft resulted in higher adhesion scores and subserosal inflammation score
than the uncovered control side. Other data showed that when heparin was
added to the amniotic membrane, it was an effective combination in reducing
Exogenous barriers such as metal foils, plastic
hoods, silk and rubber sheets were used in the past to reduce postoperative
adhesions. However, these substances have been abandoned because of lack
of success and the need for its removal by a second surgical procedure.113
Gore-Tex surgical membrane is an exogenous
barrier. It is composed of a polytetrafluoroethylene (PTFE) which is nontoxic,
non-reactive and antithrombogenic; it is not absorbed and is unaffected
by tissue enzymes.114
Therefore, it is a permanent membrane unless it is surgically removed later
on. Placement requires suturing or some other form of fixation. In the
animal studies, Gore-Tex has been proven to be an effective barrier for
reducing primary adhesions, as well as reformation of adhesions.115
This encouraged its clinical trials. March and colleagues116
carried out their study where 18 patients with extensive pelvic adhesions
and 10 with myomas had Gore-Tex applied over the adhesiolysis or myomectomy
sites. At second-look laparoscopy, the membranes were removed easily with
minimal adhesions to the traumatized site noted. However, it is common
for a membrane to envelop the PTFE. In a multicenter nonblinded randomized
clinical trial, Haney and his co-operatives117
studied 32 women with bilateral pelvic sidewall adhesions undergoing reconstructive
surgery and second-look laparoscopy. They found that Gore-Tex was associated
with fewer postsurgical adhesions to the pelvic sidewall and even superior
to oxidized regenerated cellulose (Interceed TC7). To date, third-look
studies to assess operative sites after removal of the enveloping membrane
at second-look have not been systematically performed.
Fibrin glue is a combination of highly
concentrated fibrinogen, thrombin, calcium, and factor VIII. It is postulated
that fibrin glue acts by separating the raw surfaces through its rapid
In a rat model, a reduction in intra-abdominal
adhesion formation was demonstrated with the administration of fibrin glue
with a high fibrinogen concentration (from cryoprecipitate) but not when
the fibrinogen concentration was low (from fresh frozen plasma).118
Obviously, the use of human blood products for
fibrin glue production limits its attractiveness as a surgical adjuvant.
Using rat models, a recent randomized, controlled study was carried out
by Evrard and co-workers,119
showed that although the mean adhesion score was reduced by >50% with application
of fibrin glue, there was no statistically significant difference concerning
adhesion formation or peritoneal healing with the use of fibrin glue.
Surgicel is an oxidized regenerated cellulose
(ORC) that was initially designed as a hemostatic agent. It was investigated
as an adjuvant for prevention of adhesions because it is easy to apply
and becomes a gel within hours after application. Initial studies showed
that Surgicel is effective in preventing adhesions in rat cecal trauma
However, other studies failed to realize any reduction in adhesion formation
in the same animal.122
The same controversy has been found with the use of a uterine horn model.
In spite of most studies123
that found Surgicel to be effective in preventing adhesion formation, some124
did not confirm this observation.
Interceed (TC7) is an "altered relative"
to Surgicel also composed of oxidized regenerated cellulose but differs
in several characters including its degree of oxidation, weave, and smaller
pore size. Interceed becomes a gel about eight hours after its intra-abdominal
application. The material usually cannot be identified in the field within
3-4 days, and usually is degraded by the body without evidence of a foreign
body reaction at the site of application.124
Interceed is metabolized into glucose and glucoronic acid within a few
Initial rabbit studies using a uterine horn model
showed a decrease in adhesion formation.126
This observation was confirmed by Diamond et al,127
using a sidewall model in which each animal could be its own control. These
encouraging results initiated a human clinical trial conducted by multicenters.
This study showed a significant reduction in the incidence and area of
postoperative adhesion reformation in an actual report of 74 patients,128
and a follow up report of 134 patients.130
The use of Interceed necessitates meticulous hemostasis in the area prior
to its application, otherwise it becomes ineffective. Wiseman et al129
used thrombin to achieve hemostasis in a rabbit uterine horn adhesion model
facilitating the effect of interceed barrier. They added that the efficacy
of Interceed was further enhanced by adding heparin to the fabric. A large
multicenter study included 134 patients who underwent bilateral pelvic
wall microsurgical adhesiolysis. In this study, Interceed was shown to
further reduce the incidence, extent and severity of postoperative adhesion
reformation and 90% of the patients benefits from the use of Interceed.130
To evaluate the efficacy of Interceed in prevention of postsurgical ovarian
adhesions many studies were carried out. Franklin and The Ovarian Adhesion
published a multicenter randomized study including 55 patients with bilateral
ovarian disease. One ovary was randomly wrapped with Interceed at the completion
of laparostomy and the other was left uncovered. At the time of second-look
laparoscopy, they found that treatment of ovaries with Interceed significantly
reduced the occurrence and severity of postsurgical ovarian adhesions.
As regards laparoscopic ovarian surgery, Interceed was found to be safe
and effective also in reducing the incidence of postoperative adhesion
formation in patients undergoing laparoscopic ovarian cystectomy.132
These results are consistent with those of Larsson et al.,102 who also
reported the ability of Interceed to reduce adhesions to the fallopian
tubes. In contrast, in a small study (n=21), Saravelos et al.,133
were able to demonstrate a difference in reduction of adhesions on the
Interceed-treated and control side after laparosopic electro-surgical treatment
of polycystic ovarian syndrome.
In more studies, Haney and Doty134
found that Interceed, but not Gore-Tex surgical membrane has a localized
injurious effect on the peritoneum of the mouse, resulting in de novo adhesions.
However, in these studies the Interceed wasn't moistened and a 1 cm2
piece was used in the small abdominal cavity of the mouse. In spite of
that, a recent report from the Nordic Adhesion Prevention Study Group135
showed in a randomized, multicenter, controlled study that by using a protocol
in which other adjuvants have been shown not to be efficacious, Interceed
was shown to significantly reduce the incidence and severity of adhesion
reformation to the ovary, fallopian tube, and fimbria after infertility
A modified version of Interceed is neutralized
Interceed (nTC), that is blood insensitive, has also proved efficacious
in reducing adhesion formation and reformation in animal studies.136
The results using the nTC7 Interceed are comparable to those obtained with
Interceed in combination with heparin. Further animal and human studies
are needed, but the results thus far appear quite promising.
Seprafilm is a bioresorbable membrane
composed of chemically modified sodium hyaluronate/carboxymethylcellulose.
It has been investigated recently by Diamond and The Seprafilm Adhesion
in a large randomized multicenter study, which includes 127 women who underwent
uterine myomectomy with at least one posterior uterine incision 11 cm in
length. In this study treatment of patients after myomectomy with Seprafilm
significantly reduced the incidence, severity, extent, and area of postoperative
uterine adhesions. Additionally, Seprafilm treatment was not associated
with an increase in postoperative complications.
Pelvic adhesion development after gynecological
operations and their reformation after adhesiolysis still, up until now,
a problem that presents itself in the form of infertility, pelvic pain
and/or intestinal obstruction. The following questions still need more
investigations to be answered: Why some patients are more susceptible for
adhesion formation and others are not? Can those patients be identified
pre-operatively? Which stage of adhesion formation is more suitable to
interfere with by an agent to reduce it?
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