Table Of ContentS P
CIENTIFIC APERS
Strategies to Minimize Adhesions to Intraperitoneally
Placed Mesh in Laparoscopic Ventral Hernia Repair
Hanh Tran, Lucia Saliba, Edward Chandratnam, Isidro Turingan, Wayne Hawthorne
ABSTRACT tion with both meshes. There was extensive collagen
deposition between Polypropylene mesh fibers, while fi-
Introduction: Adhesions to mesh/tacks in laparoscopic
brosis occurred on both sides of DualMesh with synovial
ventral hernia repair are often cited as reasons not to
metaplasia over its peritoneal surface akin to encapsula-
adopt its evidence-based superiority over conventional
tion.
openmethods.Thispilotstudyassessedtheoccurrenceof
adhesions to full-sized Polypropylene and Gore-tex Du- Conclusions: DualMesh caused fewer omental and vis-
alMesh Plus meshes and the possibility for adhesion pre- ceraladhesionsthanPolypropylenemeshdid.Fibrinseal-
vention using fibrin sealant. ant eliminated adhesions to DualMesh and prevented ad-
hesions to Polypropylene mesh when applied over the
Methods: Two 10-cm to 15-cm pieces of mesh were
entire surface. These results support our current use of
placed and fixed laparoscopically in pigs (25kg to 55kg).
DualMesh and fibrin sealant in LVHR.
GroupI:2animalswithPolypropylenemeshononeside
and DualMesh on other side. Group II: 2 animals with Key Words: Laparoscopy, Ventral hernia, Fibrin sealant,
DualMesh on each side with fibrin sealant applied to the
Adhesion prevention.
periphery of mesh and staples to one side. Group III: 1
animal with 2 pieces of Polypropylene mesh with fibrin
sealantappliedtotheentiremesh.Allanimalsunderwent
laparoscopy 3 months later to assess the extent of adhe-
sions, and full-thickness specimens were removed for
INTRODUCTION
histological evaluation.
Since laparoscopic ventral hernia repair (LVHR) was in-
Results: More Polypropylene mesh was involved in ad-
troducedin1989,numerousstudieshavedemonstratedits
hesions than DualMesh. However, with the DualMesh
superiority over conventional open repair, most notice-
involved in adhesions, more of the surface area was in-
able with the significant reduction in wound complica-
volved in forming adhesions than with Polypropylene
tions.1–3 Although recurrence rates of LVHR have been
mesh. None of the implanted DualMesh had visceral ad-
shown to be (cid:1)5%, it has not been possible, for ethical
hesions, while 2 out of 3 Polypropylene meshes had
reasons, to relaparoscope these patients routinely to as-
adhesions to both the liver and spleen but none to the
sess adhesion formation. It is known that all adhesions
bowel.ImplantedPolypropylenemeshwithfibrinsealant
have the potential for deleterious effects including bowel
had no adhesions. DualMesh had shrunk more signifi-
obstruction, sometimes even decades after the original
cantly than Polypropylene mesh. Histological evaluation
surgical intervention. Staples are usually used in LVHR,
showed absence of acute inflammatory response, signifi-
cantly more chronic inflammatory response to DualMesh which have been shown to act as the nidus for adhesion
comparedtoPolypropyleneandcompletemesothelializa- formation4atbestandasiteoffistulaformationatworst.5
Whileeffortsarebeingmadetousealternativeabsorbable
fixation devices as well as reducing the number of per-
UniversityofSydney,DepartmentofSurgery,WestmeadHospital,Westmead,NSW
manentstaplesbeingused,6itmaytakemanyyearsbefore
Australia(Dr.Tran,Dr.Hawthorne).
a solution, if any, is found. Yet there is current evidence
HolroydPrivateHospital,GuildfordNSWAustralia(Mr.Turingan).
availabletosuggestthat,paradoxically,fibrinsealantitself
FairfieldHospital,Fairfield,NSWAustralia(Dr.Saliba).
hasbeenshowntoreduceadhesionsinanimalmodels.7–9
AuspathLaboratories,Westmead,NSWAustralia(Dr.Chandratnam).
Addresscorrespondenceto:Dr.HanhTran,Level2,195MacquarieStreet,Sydney
Thisisafeasibilitystudythataimstoassesswhetherfibrin
NSW2000Australia.E-mail:[email protected]
sealanthasanyadhesionpreventioneffectsoncommonly
DOI:10.4293/108680812X13291597716140
used meshes in a large animal model with clinical size
©2012byJSLS,JournaloftheSocietyofLaparoendoscopicSurgeons.Publishedby
theSocietyofLaparoendoscopicSurgeons,Inc. dimensions.
JSLS(2012)16:89–94 89
StrategiestoMinimizeAdhesionstoIntraperitoneallyPlacedMeshinLaparoscopicVentralHerniaRepair,TranHetal.
MATERIALS AND METHODS seel,Baxter,Vienna).The abdomen was kept insufflated
for 5 minutes after fibrin sealant application before
ThisstudywasapprovedbytheAnimalEthicsCommittee
deflation and closure of the upper quadrant wound in
of the Sydney West Area Health Service. Permission was
layers with nylon sutures and the skin wounds with
given to use (only) 5 pigs for the purpose of studying
staples. The animals were recovered, and analgesia
adhesionpreventionoffibrinsealantduringlaparoscopic
0.01mg/kg Buprenorphine (Temgesic, Reckitt & Col-
intraperitoneal onlay mesh placement.
manProductsLtd.,Hull,UK)wasgivenevery6hoursto
8 hours for at least 48 hours then as necessary. They
Animal and Mesh Placement
were kept and fed ad libitum for the next 3 months
Five male Westran pigs of 25kg to 50kg (mean, 35.6) were without any animals experiencing distress or complica-
used (Table 1). Procedures were performed with the pigs tions.
under general anaesthetic following premedication with in-
tramuscular 1mg/kg Ilium Xylazil (Xylazine, Troy Laborato- Laparoscopic Evaluation
ries Pty. Ltd., Sydney, Australia), 25mg/kg Tiletamine com-
Threemonthslater,theanimalsunderwentrelaparoscopy
binedwith25mg/kgZolazepam(Zoletil100Virbac,Australia
wherethenumberofadhesionswereassessed.Omentum
Pty.Ltd.,Sydney,Australia)and1mg/kgAzaperone(Stresnil,
or visceral (bowel/organ) adhesions to the mesh were
Boehringer Ingelheim Pty. Ltd., Sydney, Australia). General
recorded, and adhesion tenacity was graded (0–4) intra-
anaesthesiawasmaintainedwith1%to2%Isoflourane(Aer-
operatively. The surface area (cm2) of the mesh was cal-
rane,BaxterHealthcarePtyLtd,Sydney,Australia)inoxygen
culated by measuring the cranial-caudal and transverse
after intubation. The abdomen was prepped with alcohol
dimensions(cm)oftheintraperitonealmesh.Thesurface
andBetadineskinprep,andtheanimalsunderwentlaparo-
area of adhesions covering the mesh was estimated in
scopicintraperitonealonlaymeshplacement.Briefly,a2-cm tenth percentiles (0(cid:2)0%, 10(cid:2)100%).6
incisionismadeintherightupperquadrant,andthemuscle
layersaresplituntiltheperitoneumisentered.A10-mmport
Necropsy and Histological Analysis
(Covidien,Norwalk,ConnecticutUSA)isinsertedunderdi-
rect vision. The peritoneal cavity was then insufflated with Theanimalsweretheneuthanizedbeforefull-thicknessex-
CO to12mmHg.Two5-mmportsarethenplacedlaterally cision of the meshes with their attached (if any) adhesions.
2
under direct vision, and laparoscopy is then performed to Thesewereplacedin10%Formalin,sectioned,andstained
ensure no prior intraperitoneal adhesions are present. A forhematoxylinandeosinandcollagenstains.Tworandom
10-cm to 15-cm piece of mesh, either Polypropylene samples(1cmto2cm)wereexcisedfromeachpieceofmesh
(PROLENE Mesh, Ethicon, Inc, USA) and/or Gore-tex Du- and evaluated histologically by 2 observers, blind to the
alMesh Plus (WL Gore & Associates Inc, Elkton, MD, USA) meshtypeimplanted.Thesampleswereevaluatedforacute
was placed on each side of the abdomen, and these were andchronicinflammation(polymorphonuclearleukocytes(cid:2)
fixed with transfascial sutures in 4 quadrants: 1 Gore-tex PMNs and chronic inflammatory cells(cid:2)CICs per high-pow-
suture and a double layer of titanium staples (Protacks, ered field (HPF; magnification(cid:2)40): 0–4 CICs/HPF(cid:2)1, 5–9
Covidien, Norwalk, Connecticut USA) were then applied CICs/HPF(cid:2)2, 10–15 CICs/HPF(cid:2)3 and (cid:3)15 CICs/HPF(cid:2)4,
with the staples being 1cm apart on the “outer crown” and tissue ingrowth and mesothelialization as previously de-
2cmapartonthe“innercrown.”Themeshononesideofthe scribed.10Thepredominantinflammatoryresponsecompar-
abdomenwasthensprayedwith2mLoffibrinsealant(Tis- ing acute, as exhibited by polymorphonuclear cell infiltra-
Table1.
ExperimentalDesignwiththeNumberofPigsandtheDifferentMesheswithorWithoutFibrinSealant
Group Pig# Mesh LeftSide RightSide
1 1 Polypropylene/Dualmesh Polypropylene Dualmesh
2 Dualmesh/Polypropylene Dualmesh Polypropylene
2 3 Dualmesh Dualmesh Dualmesh(cid:4)FibrinSealant
4 Dualmesh Dualmesh(cid:4)FibrinSealant Dualmesh
3 5 Polypropylene Polypropylene Polypropylene(cid:4)FibrinSealant
90 JSLS(2012)16:89–94
Figure 2. Group 2 animals showing segmental omental adhe-
sionswithDualmeshPlusandnoadhesionswithDualmeshPlus
andfibrinsealant.
Figure1.Group1animalswithPolypropyleneanimalsshowing
omental and liver adhesions with inset showing displaced sta-
ples in liver while Dualmesh Plus animals showing segmental
omentalornoadhesions.
tion,versuschronic,asexhibitedbyhistiocytic/lymphocytic/
foreignbodyreaction,wasassessed.
RESULTS
Combining the adhesion results of all 3 groups without
fibrinsealantrevealedthatalargeramountofPolypropyl-
ene mesh was involved in adhesions than DualMesh (2
SD(cid:2)0vs1SD(cid:2)0).However,oftheDualMeshinvolvedin Figure 3. Polypropylene animal showing segmental omental
adhesions, more of the surface area was involved in ad- adhesionswhilePolypropyleneandfibrinsealantanimalshow-
hesions than Polypropylene mesh (2.33 SD(cid:5)1.15 vs 1.67 ingnoadhesions.
SD(cid:5)0.58) (Figure 1 & 2). However, there were a large
numberofstaples(35%oftotal)“pulled”offthePolypro- all samples. Implanted Polypropylene meshes (with or
pylene mesh and embedded in adhesions to omentum, without fibrin sealant) showed extensive collagen depo-
liver, and spleen (Figure 1). None of the DualMesh im- sitionbetweenthemeshfibers(Figure4),whereasthere
planted showed visceral adhesions (Figure 2), while 2 was only superficial collagen infiltration into the perito-
out of 3 Polypropylene meshes had adhesions to both neal surface of implanted DualMesh (Figure 5). More
liver and spleen but none to bowel. Implanted Polypro- importantly, there was a thick layer of fibrous tissue cov-
pylene mesh with fibrin sealant had no adhesions what- ering the peritoneal surface of the DualMesh with a thick
soever (Figure 3). layer of histiocytes (known as synovial metaplasia) at the
mesh-fibrous tissue interface (Figure 5).
Implanted Polypropylene meshes showed negligible
shrinkagewithallexplantedmeshesmeasuring9.25cmto At3months,therewasacompleteabsenceofpolymorpho-
14.4cm(SD(cid:5)0.29and(cid:5)0.25,respectively)from10cmto nuclear cells in all the samples, Polypropylene and DualM-
15cmatimplantation,whileexplantedDualMeshshowed esh, with or without fibrin sealant. The mean histological
significant shrinkage to 5.3cm to 10.4cm (SD (cid:5)0.27 and score for chronic inflammation was 1.8 SD(cid:5)1.23 for Poly-
(cid:5)0.42, respectively). Histological evaluation showed propylenemeshand3.0SD(cid:5)1.33forDualMesh.Theintense
completemesothelializationovertheperitonealsurfaceof chronicinflammatorycellularinfiltration,representedbyhis-
JSLS(2012)16:89–94 91
StrategiestoMinimizeAdhesionstoIntraperitoneallyPlacedMeshinLaparoscopicVentralHerniaRepair,TranHetal.
tiocytic/lymphocytic/foreign body giant cellular infiltration, cholecystectomy, being treated almost exclusively by lapa-
was present on both surfaces of DualMesh (Figure 5). In roscopicmeans.Apartfromreducingwoundcomplications,
addition,therewereoccasionalclustersofeosinophilsin2of laparoscopyhasalsosignificantlyreduced,thoughnotabol-
3 DualMesh samples (Figure 5) but none in the Polypro- ished, intraabdominal adhesions.11 In the field of hernia
pylenesamples. surgery,anincreasingnumberofabdominalwallherniasare
being treated with intraperitoneal onlay mesh placement.
DISCUSSION Currently,therearesome270differentmeshesavailablewith
theindustryconcentratingonproducingmesheswithfewer
The advent of laparoscopy in general surgery in the late
adhesiogenic properties yet retaining their strength. Al-
1980s has seen a large number of procedures, including
thoughanimalmodels,smallandlarge,haveshownpoten-
tialbenefits,intermsofreducingadhesions,extrapolationto
humans cannot be assumed. Despite the expense of these
meshes, compared to Polypropylene mesh, almost all have
shownsignificantadhesionsinhumans.Inastudyofrelapa-
roscopyinpatientswhohadundergonelaparoscopicventral
herniarepair,Jenkinsetal6demonstratedadhesionsto60%
to100%ofmeshsurface.Ofmuchconcernwasthatintesti-
nal adhesions occurred in 64% of ePTFE mesh and up to
100% of macroporous meshes. Apart from the periphery of
the so-called anti-adhesive meshes being devoid of anti-
adhesion barrier, the protruding fixation devices also pro-
videanidusforadhesions.Althoughtheuseofabsorbable
fixation devices is becoming more common in hernia sur-
gery,itremainstobedeterminedwhethertheyaresuperior
to nonabsorbable fixation devices in humans in preventing
intraabdominal adhesions. Furthermore, their use with
Figure 4. Top pictures showing H&E stain of Polypropylene meshes such as ePTFE, known to cause much less fibrosis
mesh with adherent omentum (left) while fibrin sealant treated andintegrationintotheabdominalwall,ishighlyquestion-
Polypropylene mesh (right) with no adhesions with a neo-me- able.
sothelial layer on top of the mesh. Bottom pictures showing
On one hand, efforts have been concentrated on using
collagen stain showing collagen infiltration within the mesh
fiberswhichhadbeendissolvedduringpreparation. fibrin sealant to supplement fixation devices in ventral
Figure5.ToppicturesshowingathicklayeroffibroustissueoverlyingGortexDualmeshPlus(left)whichhadbeenfracturedoffthe
meshduringpreparation,withtheexternalmesh-fibroustissueinterfaceshowingsynovialmetaplasia(middle)withpallisadinglayer
ofhistiocytes(right).Bottompicturesshowingneo-mesotheliumcoveringthefibrintreatedGortexDualmesh(leftandmiddle)while
theroughundersurfaceofthemeshisinfiltratedwithcollagen.
92 JSLS(2012)16:89–94
herniarepair;ontheother,thereisbothexperimentaland was only given for 5 animals to be used. However, this
clinical evidence for beneficial effects of fibrin sealant in study was designed only to identify potential anti-adhe-
minimizing adhesions. Sikkink et al7 demonstrated in a sion properties of fibrin sealant in a qualitative manner.
study on rats in which abdominal wall defects were cre-
While Polypropylene mesh in this swine model did not
ated and covered with Polypropylene mesh that applica-
showanysignificantshrinkageatexplantation,DualMesh
tionoffibrinogengluesignificantlyreducedtheseverityof
showed significant shrinkage from 10cm to 15cm on im-
adhesionscomparedwithPolypropylenemeshalone.Pet-
plantationto5.5cmto10.5cmatexplantationat3months.
ter-Purchneretal8demonstratedinaratmodelthatfibrin
Histological evaluation showed a thick layer of fibrous
sealant not only reduced adhesions to implanted con-
tissue covering the parietal and peritoneal surfaces of
densed polytetrafluoroethylene mesh but also enhanced
DualMeshwithsynovialmetaplasia,representedbyapal-
tissue integration into the mesh. In large animal models,
isading layer of histiocytes, at the fibrous tissue-mesh
someencouragingresults,ontheanti-adhesionproperties
(peritoneal) surface, akin to fibrous encapsulation of
offibrinsealant,havealsobeenreported.Martin-Carteset
breast implants.12 This could therefore be the reason for
al9 demonstrated in a swine model that, both ePTFE and
the significant shrinkage of DualMesh. There was a com-
Polypropylene, meshes placed intraabdominally, via lap-
pleteabsenceofacutecellularinfiltrationwithbothmesh
arotomy,reducedbothquantityandconsistencyofadhe-
typesat3months.Therewasonlysparsechroniccellular
sions following application with fibrin sealant. Our pilot
infiltration in Polypropylene mesh samples, predomi-
studyinaswinemodelreplicatesmorecloselythehuman
nantly associated with mesh fragments, while this was
model in that the operation was performed exactly as in
quite intense around DualMesh. In addition, 2 of 3 Du-
humans with clinical size (large) meshes being used. We
alMesh samples had small clusters of eosinophils signify-
demonstrated that while Polypropylene mesh produced
ing a potential allergic reaction.
quantitatively more adhesions than DualMesh with the
former causing adhesions to the liver/spleen, fibrin seal- Because this was a pilot study, permission was given to
ant abolished adhesions, to not only DualMesh, but sur- use only 5 animals, therefore preventing any statistically
prisingly to Polypropylene mesh. Admittedly, 6mL of fi- conclusive statements to be made on the adhesion pre-
brin sealant was used on the Polypropylene implanted vention effects of fibrin sealant. Furthermore, the authors
animal, compared to DualMesh groups, where only 2mL purposefullydidnotseekanycommercialsupportforthe
was used. This was to ensure that the entire Polypropyl- project in order to prevent any bias, perceived or other-
ene mesh including the staples were completely covered wise, or worse prevention of publication of the results of
with fibrin sealant, compared to the DualMesh group, this project should they turn out to be negative. Despite
where only the exposed periphery of the mesh and sta- the limitation imposed by the small number of animals,
plesweresprayedwithfibrinsealant.Itisunfortunatethat these exciting results permit us, and possibly other re-
onlyonepigwasusedinthiscomparison,butpermission searchgroups,toobtainfurtherapprovalforamorequan-
Figure 6. Patient with previous LVHR (left) presented with bilateral inguinal hernias and underwent single incision laparoscopic
inguinalherniarepair(inset).Intraperitonealview(right)ofpreviousimplantedDualmeshwhichhadbeensprayedwithfibrinsealant
alongperipheryofmeshandstaplesshowingnoadhesions.
JSLS(2012)16:89–94 93
StrategiestoMinimizeAdhesionstoIntraperitoneallyPlacedMeshinLaparoscopicVentralHerniaRepair,TranHetal.
titative study where a larger number of animals (prefera- References:
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94 JSLS(2012)16:89–94
