Prolapse SurgeryProlapse SurgeryProlapse SurgeryProlapse SurgeryHow to HandleHow to Handle“Innovations”“Innovations”

Polypropylene Is Not Inert in Polypropylene Is Not Inert in the Human Bodythe Human Body

Donald R. Ostergard, MDDonald R. Ostergard, MDUniversity of California IrvineUniversity of California IrvineUniversity of California, IrvineUniversity of California, Irvine

Long Beach Memorial Medical CenterLong Beach Memorial Medical Center

Medical Marketing ers s ScienceMedical Marketing ers s ScienceMedical Marketing versus Science Medical Marketing versus Science with New Procedures and Graftswith New Procedures and Grafts

P l l M h G ftP l l M h G ftPolypropylene Mesh Grafts:Polypropylene Mesh Grafts:What Influences Erosion What Influences Erosion vs. Tissue Incorporation? vs. Tissue Incorporation?

Wh t i th M j I ?Wh t i th M j I ?What is the Major Issue?What is the Major Issue?Traditional Surgery with SutureTraditional Surgery with SutureTraditional Surgery with SutureTraditional Surgery with Suture

vs.vs.“Innovative” Surgery with Mesh Kits“Innovative” Surgery with Mesh Kits“Innovative” Surgery with Mesh Kits“Innovative” Surgery with Mesh Kits

($1000($1000--3000 per kit)3000 per kit)

Physicians need to knowPhysicians need to knowrelative benefits and risksrelative benefits and risks

using evidence based medicine:using evidence based medicine:ggWhich mesh or procedure is best?Which mesh or procedure is best?

Should Mesh Be Used Should Mesh Be Used I All P i ?I All P i ?In All Patients?In All Patients?

3737--100% of traditional anterior 100% of traditional anterior 3737 100% of traditional anterior 100% of traditional anterior repairs are successfulrepairs are successfulRecent reports indicate 81Recent reports indicate 81 88%88%Recent reports indicate 81Recent reports indicate 81--88%88%3737--100% of primary patients have 100% of primary patients have

h i t d th d t d h i t d th d t d mesh inserted they do not need mesh inserted they do not need 10% return to the operating room 10% return to the operating room for removal with substantial for removal with substantial morbiditymorbidity

Maher C et al. Int Urogynecol J Pelvic Floor Dysfunct. 2006;17:195-201.Kapoor DS, et al. Int Urogynecol J 2010;21:27-31.Meschia M, et al. J Urol 2007;177:192-195

Cystocele RepairCystocele RepairS M hS M hSuture vs. MeshSuture vs. Mesh

Randomized prospective Randomized prospective Randomized, prospective Randomized, prospective comparative trialscomparative trialsEither no statistically significant Either no statistically significant Either no statistically significant Either no statistically significant difference ordifference or——A i ifi t diff f A i ifi t diff f A significant difference for A significant difference for anatomical correction for the meshanatomical correction for the meshBut, quality of life questionnaires are But, quality of life questionnaires are not significantly differentnot significantly different

Nguyen JN, Burchette RJ. Obstet Gynec 2008;111:891-898

Standard Anterior Repair vsStandard Anterior Repair vsA i R i i h M hA i R i i h M hAnterior Repair with MeshAnterior Repair with Mesh

Prospective, randomized, controlled Prospective, randomized, controlled Prospective, randomized, controlled Prospective, randomized, controlled clinical trialclinical trialAnt/post repair with mesh vs Ant/post repair with mesh vs Ant/post repair with mesh vs Ant/post repair with mesh vs traditional colporrhaphiestraditional colporrhaphies70 patients in each group70 patients in each group70 patients in each group70 patients in each groupAfter 1 year, no statistically After 1 year, no statistically significant difference between groups significant difference between groups significant difference between groups significant difference between groups for recurrent prolapsefor recurrent prolapseSame rate of dyspareuniaSame rate of dyspareuniaSame rate of dyspareuniaSame rate of dyspareuniaCarey M et al. BJOG 2009;116:1380-86.

Cystocele RepairCystocele RepairS M hS M hSuture vs. MeshSuture vs. Mesh

There is no Level 1 evidence to There is no Level 1 evidence to There is no Level 1 evidence to There is no Level 1 evidence to support the use of mesh in any support the use of mesh in any vaginal compartmentvaginal compartmentvaginal compartmentvaginal compartmentInternational societies and individual International societies and individual authorities are stating: “There is no authorities are stating: “There is no authorities are stating: There is no authorities are stating: There is no evidence that mesh should be used evidence that mesh should be used in all prolapse surgeries”in all prolapse surgeries”in all prolapse surgeries .in all prolapse surgeries .

Davila W, et al. Int Urogynecol J 2006;17:S51-S55Fit G ld MP J U l 2010 183 430 432FitzGerald MP. J Urol 2010;183:430-432.

Review the Evidence Review the Evidence f G f U i P l i P lf G f U i P l i P lfor Graft Usage in Pelvic Prolapse for Graft Usage in Pelvic Prolapse

Jia, X et al. Systematic review of the efficacy and safety of using mesh or

f i f i d/ grafts in surgery for anterior and/or posterior vaginal wall prolapse NATIONAL INSTITUTE FOR HEALTH NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE(of the United Kingdom) (of the United Kingdom) (of the United Kingdom) (of the United Kingdom)

224 pages! June 08224 pages! June 08www.NICE.org.ukg

NICE Conclusions NICE Conclusions -- June 2008 June 2008 224224 4 69 W4 69 W224 pages 224 pages –– 4569 Women4569 Women

“Too few data reported for any of the Too few data reported for any of the efficacy outcomes”“T f d t f t t ”“Too few data on safety outcomes”“No firm conclusions could be drawn about the effectiveness of any of the mesh/graft types compared to no mesh for anterior and/or posterior repair”

In the Early 1990’s We Stepped In the Early 1990’s We Stepped O V I LiO V I LiOver a Very Important LineOver a Very Important LineTRADITIONAL “INNOVATIVE”

Anterior repair

Kellyplication

ProliftTM

TVT TM

plication

TOT TM

Apogee/Perigee TM

Posterior repair

Enterocele

McCall culdoplasty

Elevate TM

Enterocele repair

AvaultaTM

Who Controls Our Thoughts and Who Who Controls Our Thoughts and Who T h U N S i l P d ?T h U N S i l P d ?Teaches Us New Surgical Procedures?Teaches Us New Surgical Procedures?

Previously, physicians and sciencePreviously, physicians and scienceNow, industry control and marketingNow, industry control and marketingTeaching by industry representatives Teaching by industry representatives g y y pg y y pin the operating roomin the operating roomSometimes the company sends a Sometimes the company sends a Sometimes the company sends a Sometimes the company sends a physician proctorphysician proctor

What Kinds of Synthetic Grafts are What Kinds of Synthetic Grafts are d i P l S ?d i P l S ?used in Prolapse Surgery?used in Prolapse Surgery?

Type I: Macroporous: Type I: Macroporous: P 75 iP 75 i––Pores >75 micronsPores >75 microns

––Most prolapse grafts in current use, Most prolapse grafts in current use, MarlexMarlexMarlexMarlex

Subdivision by mesh weightSubdivision by mesh weight––Light weight = <50Light weight = <50--60 gm/m60 gm/m22

––Heavy weight = >60 gm/mHeavy weight = >60 gm/m22

Amid P. Hernia 1997;1:15-21

What Kinds of Synthetic Grafts are What Kinds of Synthetic Grafts are d i P l S ?d i P l S ?used in Prolapse Surgery?used in Prolapse Surgery?

Type II: Microporous:Type II: Microporous:Type II: Microporous:Type II: Microporous:––Pores =/<10 micronsPores =/<10 microns

Go eGo e Te Te ––GoreGore--Tex Tex

Type III: Microporous with Type III: Microporous with t tmacroporous componentsmacroporous components

––ObTape, MersileneObTape, Mersilene

Type IV: Totally nonporousType IV: Totally nonporous––SilasticSilastic

Amid P. Hernia 1997;1:15-21

What is the Best Mesh?What is the Best Mesh?What is the Best Mesh?What is the Best Mesh?MacroporousMacroporouspp?Polypropylene vs. polyester?Polypropylene vs. polyester(polyethelyene terephthalate)(polyethelyene terephthalate)(p y y p )(p y y p )--Mersilene (reconfigured)Mersilene (reconfigured)Light weight = <50Light weight = <50--60 gm/m60 gm/m22g gg g g /g /--Most currently used meshesMost currently used meshesHeavy Weight = >60 Heavy Weight = >60 gm/mgm/m22Heavy Weight >60 Heavy Weight >60 gm/mgm/m--Marlex (95)Marlex (95)--Surgipro SPM, IVS (85);Surgipro SPM, IVS (85);Surgipro SPM, IVS (85);Surgipro SPM, IVS (85);

Anatomy of a Macroporous Anatomy of a Macroporous M fil M hM fil M hMonofilament MeshMonofilament Mesh

INTERSTITIUM

PORE>75 µ

LARGE CALIBER MONOFILAMENT POLYPROPYLENE FIBERS

About 150 µ diameter

Deprest

Monofilament Mesh WeavesMonofilament Mesh WeavesMonofilament Mesh WeavesMonofilament Mesh Weaves

ARISMentor

AUTO SUTURECovidien, Parietex

TVT-O URETEX

AVAULTABard

TVT-OGynecare

URETEXBard

Which one has the greatest surface area?

A Microporous Multifilament Mesh With A Microporous Multifilament Mesh With M C t (IVS)M C t (IVS)Macroporous Components (IVS)Macroporous Components (IVS)

LargePore

Multi-filamentsmalldiameterdiameterfibers20-40 µ

SmallerPore

Greatlyincreasessurface area

MicroPores

area

Weight=85 g/m2

Slack M, et al. Int Urogynecol J 2006; 17:106-10.

85 g/m

A Microporous Multifilament Mesh: A Microporous Multifilament Mesh: H W ld d (ObT )H W ld d (ObT )Heat Welded (ObTape)Heat Welded (ObTape)

Multi-Multifilamentwithgreatlyi d

Non-KnittedNon-woven

increasedsurface area

“Cul de Sac”Blind pores

Multi-filament with greatly increased surface areaSlack M, et al. Int Urogynecol J 2006; 17:106-10.

FDA 510 (k) Clearance Process for FDA 510 (k) Clearance Process for N D i (M h)N D i (M h)New Devices (Mesh)New Devices (Mesh)

The FDA does not approve new The FDA does not approve new The FDA does not approve new The FDA does not approve new devices or surgical proceduresdevices or surgical proceduresThe FDA clears devices for marketingThe FDA clears devices for marketingThe FDA clears devices for marketingThe FDA clears devices for marketingThe manufacturer must claim The manufacturer must claim i il it t di t d i th t i il it t di t d i th t similarity to a predicate device that similarity to a predicate device that

the FDA has already clearedthe FDA has already clearedMust be similar in planned usage and Must be similar in planned usage and technological characteristicstechnological characteristics

Guidance for the preparation of a premarket notification application for a surgical mesh.

March 2, 1999. HHS Publication FDA 95-4158

Predicate Device New DevicePredicate Device New DevicePredicate Device New Device Predicate Device New Device IVS

TVT

OBTAPE

Where are the similarities?

Manufacturer’s RequirementsManufacturer’s RequirementsFor FDA ClearanceFor FDA ClearanceFor FDA ClearanceFor FDA Clearance

No need to show rates of success or No need to show rates of success or o eed to s o ates o success oo eed to s o ates o success oadverse eventsadverse eventsNo need to study in animals or humansNo need to study in animals or humansNo need to prove that it treats what it is No need to prove that it treats what it is intended to treatintended to treatO l d t l i b t t th t it O l d t l i b t t th t it Only need to claim, but not prove, that it Only need to claim, but not prove, that it is substantially equivalent to a material is substantially equivalent to a material previously cleared for marketing by the previously cleared for marketing by the previously cleared for marketing by the previously cleared for marketing by the FDAFDAManufacturers want you to believe that Manufacturers want you to believe that h d d dh d d dtheir product is FDA approved and inerttheir product is FDA approved and inert

Clinical Graft Material ConcernsClinical Graft Material ConcernsClinical Graft Material ConcernsClinical Graft Material Concerns

Related to its foreign body natureRelated to its foreign body natureRelated to its foreign body natureRelated to its foreign body nature--erosion vs. tissue incorporationerosion vs. tissue incorporation--migration migration --migration migration --nonnon--inertinert

j ti b i ti j ti b i ti --rejection by immune reaction rejection by immune reaction --infectioninfection

What graft characteristics What graft characteristics influence these events?influence these events?

Graft Characteristics InfluencingGraft Characteristics InfluencingE i Ti I iE i Ti I iErosion vs. Tissue IncorporationErosion vs. Tissue IncorporationPore size: macroPore size: macro-- or or

i i Wicking of fluids and Wicking of fluids and b t ib t imicro porousmicro porous

Pore depthPore depthType of mesh: multiType of mesh: multi--

bacteriabacteriaSurface characterSurface characterDegradationDegradationypyp

or monoor mono--filamentfilamentNeovascularization:Neovascularization:Amount allowedAmount allowed

ggToxic polypropylene Toxic polypropylene compoundscompoundsWeight per unit areaWeight per unit areaAmount allowedAmount allowed

Surface areaSurface areaRigidityRigidityElasticityElasticity

Weight per unit areaWeight per unit areaBrittlenessBrittlenessOxidationOxidationIndividual patient Individual patient ElasticityElasticity

ShrinkageShrinkageEncapsulationEncapsulation

Individual patient Individual patient responses: high or low responses: high or low responderresponderSurgical techniqueSurgical techniqueImmune reaction?Immune reaction? Surgical techniqueSurgical technique

Mileau For Graft InsertionMileau For Graft InsertionMileau For Graft InsertionMileau For Graft Insertion

Transvaginal placement through a Transvaginal placement through a Transvaginal placement through a Transvaginal placement through a “clean/contaminated” area“clean/contaminated” areaIt is impossible to avoid bacterial It is impossible to avoid bacterial It is impossible to avoid bacterial It is impossible to avoid bacterial contamination even with antibiotics contamination even with antibiotics used intravenously, by irrigation or used intravenously, by irrigation or y, y gy, y gby graft soaksby graft soaksStudies have shown equal Studies have shown equal qqeffectiveness of parenteral vs. topical effectiveness of parenteral vs. topical antibioticsantibiotics

Culligan P, et al. Infect Dis Obstet Gynecol 2003;11:161-5.Troy MG, et al. Am J Surg 1996;171:391-3.

Vollebregt A, et al. Int Urogynecol J 2009;20:1345-51

“The Race For The Mesh Surface”“The Race For The Mesh Surface”The Race For The Mesh SurfaceThe Race For The Mesh Surface

Once inserted the race begins Once inserted the race begins Once inserted the race begins Once inserted the race begins between the host defenses and the between the host defenses and the bacteriabacteriaIf the bacteria win, the graft is If the bacteria win, the graft is irreversibly contaminatedirreversibly contaminatedyyBacteria encase themselves in a Bacteria encase themselves in a slime which frustrates host defensesslime which frustrates host defensesBacteria have been found on mesh Bacteria have been found on mesh surfaces 6 years after insertionsurfaces 6 years after insertionyy

Gristina AG. Science 1987;237:1588-95 Klosterhalfen B, et al. Expert Rev Med Devices 2005;2:103-117.

What Influences Amount of What Influences Amount of B i l C i i ?B i l C i i ?Bacterial Contamination?Bacterial Contamination?

The greater the surface area the greater The greater the surface area the greater g gg gthe amount of bacterial attachmentthe amount of bacterial attachmentMultifilament mesh has a 205% increase Multifilament mesh has a 205% increase of surface area compared to a of surface area compared to a of surface area compared to a of surface area compared to a monofilament meshmonofilament meshBacteria can still be harbored in the <10µ Bacteria can still be harbored in the <10µ i t ti f fil t h i t ti f fil t h interstices of monofilament mesh even interstices of monofilament mesh even though it has a greater degree of though it has a greater degree of neovascularizationneovascularizationBacteria 1µ, WBC 9Bacteria 1µ, WBC 9--15µ, macrophages 15µ, macrophages 1616--20µ20µ

Klosterhalfen B, et al. Expert Rev Med Devices 2005;2:103-117.

Klinge U, et al. J Biomed Mat Res 2002;63:765-71.

Polypropylene WickingPolypropylene WickingPolypropylene WickingPolypropylene Wicking

Fluids and bacteria wick along its surfaceFluids and bacteria wick along its surfaceFluids and bacteria wick along its surfaceFluids and bacteria wick along its surfaceThe greater the surface area the greater The greater the surface area the greater the wickingthe wickingt e c gt e c gLike the Dalkon Shield IUDLike the Dalkon Shield IUDStarts during insertionStarts during insertionStarts during insertionStarts during insertionMay occur after erosion, particularly when May occur after erosion, particularly when the mesh encapsulates to contaminate it the mesh encapsulates to contaminate it the mesh encapsulates to contaminate it the mesh encapsulates to contaminate it throughout its lengththroughout its lengthAccelerated by surface roughnessAccelerated by surface roughnessy gy g

Markus RK, et al. J Chromatogr A 2003;986:17-31.Mahmoud WM, et al. J Biomat Sci Polym Ed 1993;4:567-78.Coughlin RW, et al. J Miobat Sci Polym Ed 1999;10:827-44.Bank H, et al. Contraception 1984;29:65-74.

I P l lI P l lIs PolypropyleneIs PolypropyleneInert?Inert?Inert?Inert?

Polypropylene Surface ChangesPolypropylene Surface ChangesPolypropylene Surface ChangesPolypropylene Surface ChangesSmooth pre-implantation

surface

Peeling

Denuded

Peeling

CrackingWhere is all this peeledpolypropylene going? Costello CR, et al. J Biomat Res B Appl Biomater 2007;83:44-9.

Polypropylene Degradation Polypropylene Degradation K i 1986K i 1986

Polypropylene Degradation Known Since 1986

Known in 1986Known in 1986

Degradation of In Vivo Degradation of In Vivo P l l i h F FP l l i h F FPolypropylene with Free FragmentsPolypropylene with Free Fragments

Degradation occurs by oxidationDegradation occurs by oxidationg yg yA large surface area incites more inflammationA large surface area incites more inflammationThis results in more oxidation since more This results in more oxidation since more macrophages are presentmacrophages are presentmacrophages are presentmacrophages are presentMacrophages secrete hydrogen peroxide and Macrophages secrete hydrogen peroxide and hypochlorous acid to oxidize the meshhypochlorous acid to oxidize the mesh

↓↓

Mesh become brittleMesh become brittleCan polypropylene be completely degraded?Can polypropylene be completely degraded?Where does it go?Where does it go?Where does it go?Where does it go?Does it incite a true immune reaction resulting in Does it incite a true immune reaction resulting in erosion by actual rejection of the mesh?erosion by actual rejection of the mesh?

Costello CR, et al. J Biomat Res B Appl Biomater 2007;83:44-9.

Rate of Vaginal Mesh DegradationRate of Vaginal Mesh DegradationRate of Vaginal Mesh DegradationRate of Vaginal Mesh Degradation

Low weightLow weight 21%21%Low weightLow weight 21%21%High weightHigh weight 48%48%NonNon--knitted Non wovenknitted Non wovenNonNon--knitted, Non wovenknitted, Non woven

ObTapeObTape 100%100%M ltifil tM ltifil tMultifilamentMultifilament

IVSIVS 75%75%Polyethylene Polyethylene TerephthalateTerephthalate 0%0%

Clave A et al. Int Urogynelcol J 2010;21:261-270

What Influences Erosion?What Influences Erosion?What Influences Erosion?What Influences Erosion?Quiescent infection become activeQuiescent infection become activeQQRigidity and degree of elasticityRigidity and degree of elasticityA nonA non--incorporated rigid multifilament incorporated rigid multifilament microporous mesh fixed in tissue at both microporous mesh fixed in tissue at both microporous mesh fixed in tissue at both microporous mesh fixed in tissue at both ends (TOT) cannot move with the patient’s ends (TOT) cannot move with the patient’s normal physical activitiesnormal physical activitiesSince the capsule can move, mechanical Since the capsule can move, mechanical erosion can occur as the fixed mesh erosion can occur as the fixed mesh irritates the capsuleirritates the capsuleirritates the capsuleirritates the capsuleOnce erosion occurs bacteria can be Once erosion occurs bacteria can be wicked into the unincorporated meshwicked into the unincorporated mesh

Klosterhalfen B, et al. Expert Rev Med Devices 2005;2:103-117.Dietz HP, et al.. Int Urogynecol J 2003;14:239-43.Slack M, et al. Int Urogynecol J 2006; 17:106-10.

Other Factors Influencing ErosionOther Factors Influencing ErosionOther Factors Influencing ErosionOther Factors Influencing Erosion

Hypoestrogenism is assumed to be a Hypoestrogenism is assumed to be a ypoest oge s s assu ed to be aypoest oge s s assu ed to be afactor, but there is no evidence in the factor, but there is no evidence in the literature to support thisliterature to support thisA bbi d ld d A bbi d ld d A rabbit study could not demonstrate A rabbit study could not demonstrate statistical significance in the occurrence of statistical significance in the occurrence of erosion based on estrogen statuserosion based on estrogen statuserosion based on estrogen statuserosion based on estrogen statusIf the vaginal walls are thinned or actually If the vaginal walls are thinned or actually penetrated during insertion, erosion may penetrated during insertion, erosion may occur occur –– especially the fornices during TOT especially the fornices during TOT proceduresprocedures

Higgins EW, et al. Am J Obstet Gynec 2009;201:505.e1-9.

Other Complications: Other Complications: Mesh Contracture, Pelvic Pain AndMesh Contracture, Pelvic Pain AndMesh Contracture, Pelvic Pain And Mesh Contracture, Pelvic Pain And

DyspareuniaDyspareuniaIt has been know since 1997 that mesh It has been know since 1997 that mesh contracts at least 20% in 10 monthscontracts at least 20% in 10 monthsIn 1998 contracture of 30In 1998 contracture of 30--50% was found 50% was found at 4 weeksat 4 weeksat 4 weeksat 4 weeksA recent study reported 10% per year A recent study reported 10% per year with an 85% contracture at 8 yearswith an 85% contracture at 8 yearsThe tubular vagina constricts and shortens The tubular vagina constricts and shortens causing dyspareuniacausing dyspareuniaNerve fibers are entrapped in the Nerve fibers are entrapped in the Nerve fibers are entrapped in the Nerve fibers are entrapped in the shrinking fibrous tissue causing painshrinking fibrous tissue causing painNeuromas may formNeuromas may form

Klosterhalfen B et al.. Expert Rev Med Devices 2:103-117, 2005.Klinge U, et al. Eur J Surg 1998;164:965-9.Letouzey V, et al. Int Urogynecol J 2009;20 (Suppl 2):S205-6 (Abstract).Feiner B, Maher C. Obstet Gynec 2010;115:325-330.

Mesh Contracture And PainMesh Contracture And PainMesh Contracture And PainMesh Contracture And Pain

The central body of The central body of The central body of The central body of the large mesh the large mesh contracts putting contracts putting tension on the tension on the mesh arms mesh arms

h d i tih d i tianchored in tissueanchored in tissueThis creates pain This creates pain and vaginal and vaginal and vaginal and vaginal contracturecontracture

Pre-insertion Post-insertion

Feiner B, Maher C. Obstet Gynec 2010;115:325-330.

What Causes Mesh Contracture?What Causes Mesh Contracture?What Causes Mesh Contracture?What Causes Mesh Contracture?

Larger mesh volumes cause greater Larger mesh volumes cause greater g gg ginflammatory reactionsinflammatory reactionsMore fibrous tissue is produced which More fibrous tissue is produced which continues with relentless noncontinues with relentless non--modifiable modifiable continues with relentless noncontinues with relentless non modifiable modifiable contracture over timecontracture over timeOne author recently commented that “it is One author recently commented that “it is th ift th t k i ith ift th t k i i ” ” f f the gift that keeps on givingthe gift that keeps on giving” ” for for which there is no curewhich there is no cureMesh removal is fraught with many Mesh removal is fraught with many Mesh removal is fraught with many Mesh removal is fraught with many hazards and total removal may require hazards and total removal may require many surgical proceduresmany surgical proceduresSome have culminated in neoSome have culminated in neo vaginasvaginasSome have culminated in neoSome have culminated in neo--vaginasvaginas

FitzGerald MP. J Urol 2010;183:431-2.

Individual Patient Responses to Individual Patient Responses to M h I iM h I iMesh InsertionMesh Insertion

Each individual is uniqueEach individual is uniqueEach individual is uniqueEach individual is uniqueLow responders will experience Low responders will experience minimal adverse eventsminimal adverse eventsminimal adverse eventsminimal adverse eventsHigh responders develop more than High responders develop more than

l l usual responsesusual responsesIt is not possible to categorize It is not possible to categorize individual patients at this timeindividual patients at this timeHigh tumor necrosis factor??High tumor necrosis factor??gg

FDA Mesh Complications FDA Mesh Complications MAUDE Data Base MAUDE Data Base –– www.fda.govwww.fda.gov

P t G TM ll d d FDA d b dProteGenTM recalled and FDA agreed based on 34 patients without knowledge of the denominator

TVTTVT ObTObT SS MMTVTTVT ObTapeObTape SparcSparc MonarcMonarc

RecordsRecords 495495 236236 6565 1818

Deaths (6)Deaths (6) 1%1% 00 00 00Deaths (6)Deaths (6) 1%1% 00 00 00

Bowel PerforationBowel Perforation 4%4% 00 4%4% 00

Late Bladder PerfLate Bladder Perf 7%7% <1%<1% 9%9% 00

Urethral ErosionUrethral Erosion 3%3% 00 9%9% 00

FistulaFistula *<1%*<1% 00 00 **6%**6%

Vascular InjuryVascular Injury 11%11% 1%1% 3%3% 00Vascular InjuryVascular Injury 11%11% 1%1% 3%3% 00

Vaginal ErosionVaginal Erosion 7%7% 67%67% 54%54% 33%33%

AbscessAbscess 00 20%20% 00 00

PainPain <1%<1% 1%1% 19%19% 61%61%

*Urethral, **Ureteral

FDA MAUDE Data Base FDA MAUDE Data Base -- Apogee/PerigeeApogee/PerigeeP t G TM ll d d FDA d b dProteGenTM recalled and FDA agreed based on

34 patients without knowledge of the denominator

ReportsReports 4545Bowel PerforationBowel Perforation 6%6%Bowel PerforationBowel Perforation 6%6%Ureteral FistulaUreteral Fistula 2%2%Vaginal ErosionVaginal Erosion 47%47%Vaginal ErosionVaginal Erosion 47%47%PainPain 24%24%D iD i 20%20%DyspareuniaDyspareunia 20%20%“Concrete”“Concrete” 4%4%

49 hospitalizations required for complications

Fiscal and Other Problems forFiscal and Other Problems forFiscal and Other Problems for Fiscal and Other Problems for PhysiciansPhysicians

Without data = experimentalWithout data = experimentalExperimental proceduresExperimental proceduresp pp p

--No health care insurance paymentNo health care insurance payment--Return of payment demandReturn of payment demandN l ti N l ti --No malpractice coverageNo malpractice coverage

Aetna insurance company requires Aetna insurance company requires controlled clinical trials in peercontrolled clinical trials in peer--reviewed reviewed controlled clinical trials in peercontrolled clinical trials in peer reviewed reviewed literature to be nonliterature to be non--experimentalexperimentalOther than possibly the TVT, is such Other than possibly the TVT, is such information available?information available?information available?information available?

MedicoMedico--legallegalMedicoMedico legal legal ConcernsConcerns

If you get sued for If you get sued for l h ll bl h ll bmalpractice what will be malpractice what will be read to you in the read to you in the

courtroomcourtroomcourtroomcourtroom------

American College of Obstetricians and Gynecologists, Committee Opinion, Committee on Ethics. Innovative Practice: Ethical Guidelines. Obstet Gynec (2006);108:1762-1771.

ACOG Ethical GuidelinesACOG Ethical GuidelinesACOG Ethical GuidelinesACOG Ethical Guidelines

“Without an adequate evidence base, “Without an adequate evidence base, Without an adequate evidence base, Without an adequate evidence base, practitioners cannot determine practitioners cannot determine whether an innovative technique is whether an innovative technique is qqthe most safe and effective method the most safe and effective method for treating a patient”for treating a patient”“Without adequate data on the risks “Without adequate data on the risks and benefits of new treatments, and benefits of new treatments,

ti t bl t id t ti t bl t id t patients are unable to provide a true patients are unable to provide a true informed consent”informed consent”

American College of Obstetricians and Gynecologists, Committee Opinion, Committee on Ethics. Innovative Practice: Ethical Guidelines. Obstet Gynec (2006);195:1762-1771.

American College of Obstetricians and Gynecologists Practice Bulletin Pelvic American College of Obstetricians and Gynecologists, Practice Bulletin, Pelvic Organ Prolapse. Obstet Gynec (2007);109:461-473.

ACOG Practice BulletinACOG Practice BulletinP l i O P lP l i O P l F b 200F b 200Pelvic Organ ProlapsePelvic Organ Prolapse——Feb 2007Feb 2007

Despite lack of riskDespite lack of risk--benefit benefit information, many new techniques information, many new techniques , y q, y qand products are being incorporated and products are being incorporated rapidly into clinical practice, even rapidly into clinical practice, even p y p ,p y p ,while continuous modifications are while continuous modifications are taking place in an attempt to reduce taking place in an attempt to reduce g p pg p pcomplicationscomplications----------

ACOG Practice BulletinACOG Practice BulletinP l i O P lP l i O P l F b 200F b 200Pelvic Organ ProlapsePelvic Organ Prolapse——Feb 2007Feb 2007Given the limited data and frequent Given the limited data and frequent G e t e ted data a d eque tG e t e ted data a d eque tchanges in the marketed products……the changes in the marketed products……the procedures should be considered procedures should be considered experimental patients should consent experimental patients should consent experimental…..patients should consent experimental…..patients should consent with that understanding.with that understanding.This practice bulletin was withdrawn and This practice bulletin was withdrawn and This practice bulletin was withdrawn and This practice bulletin was withdrawn and was reprinted in September ’07was reprinted in September ’07Given the limited data and frequent Given the limited data and frequent changes in the marketed changes in the marketed products……patients should consent.. products……patients should consent.. knowing the lack of long term dataknowing the lack of long term dataknowing the lack of long term data.knowing the lack of long term data.

Edit i lEdit i lEditorialEditorialMarketed vaginal mesh kits: Marketed vaginal mesh kits: rampant experimentation or rampant experimentation or rampant experimentation or rampant experimentation or improved quality of care?improved quality of care?

Nygaard I. Int Urogynecol J 2007;18:483-484

FDA Public Health FDA Public Health Notification:Notification:

O t b 21 2008O t b 21 2008October 21, 2008October 21, 2008Serious Complications Associated Serious Complications Associated with Transvaginal Placement of with Transvaginal Placement of ggSurgical Mesh in Repair of Pelvic Surgical Mesh in Repair of Pelvic

Organ Prolapse and Stress Organ Prolapse and Stress Organ Prolapse and Stress Organ Prolapse and Stress IncontinenceIncontinence

http://www.fda.gov/cdrh/safety/102008-surgicalmesh.html

FDA RecommendationsFDA RecommendationsFDA RecommendationsFDA RecommendationsPhysicians should:Physicians should:yy–– Obtain specialized training for each mesh Obtain specialized training for each mesh

placement technique, placement technique, and be aware of its and be aware of its risksrisks

–– Be vigilant for adverse eventsBe vigilant for adverse events–– Watch for complication of the placement tools Watch for complication of the placement tools

(bowel, bladder, vessels)(bowel, bladder, vessels)( , , )( , , )–– Tell patients that placement is permanent and Tell patients that placement is permanent and

that that complications may not be treatablecomplications may not be treatable–– Tell patients about QoL complications (pain, Tell patients about QoL complications (pain, Tell patients about QoL complications (pain, Tell patients about QoL complications (pain,

vaginal scarring, dyspareunia)vaginal scarring, dyspareunia)–– Provide written copy of patient labeling from Provide written copy of patient labeling from

the meshthe mesht e est e es

FDA RecommendationsFDA RecommendationsFDA RecommendationsFDA Recommendations

Physicians should: “…for each Physicians should: “…for each Physicians should: …for each Physicians should: …for each mesh”…“be aware of its risks.”mesh”…“be aware of its risks.”The only source of risk information is The only source of risk information is The only source of risk information is The only source of risk information is the manufacturerthe manufacturerThis requires evidence based clinical This requires evidence based clinical This requires evidence based clinical This requires evidence based clinical trialstrialsWill the manufacturers do what is Will the manufacturers do what is Will the manufacturers do what is Will the manufacturers do what is necessary to provide this necessary to provide this information?? information??

FDA Information for PatientsFDA Information for PatientsFDA Information for PatientsFDA Information for Patients

8 questions are given for the patient 8 questions are given for the patient 8 questions are given for the patient 8 questions are given for the patient to ask the physician, including:to ask the physician, including:––Pros and cons of using meshPros and cons of using mesh––Pros and cons of using meshPros and cons of using mesh––Can repair be done without mesh?Can repair be done without mesh?

What’s your experience:What’s your experience:––What s your experience:What s your experience:With this mesh?With this mesh?In dealing with complications?In dealing with complications?In dealing with complications?In dealing with complications?

––Can the mesh be removed for Can the mesh be removed for complications?complications?complications?complications?

Future Decision MakingFuture Decision MakingFuture Decision MakingFuture Decision Making

Given the lack of evidence based Given the lack of evidence based Given the lack of evidence based Given the lack of evidence based medicine for effectiveness and medicine for effectiveness and adverse events:adverse events:adverse events:adverse events:For a female surgeon: would you For a female surgeon: would you want this procedure done on you?want this procedure done on you?want this procedure done on you?want this procedure done on you?For a male surgeon: would you want For a male surgeon: would you want thi d d th thi d d th this procedure done on your mother, this procedure done on your mother, wife or sister?wife or sister?

Are we guessing about the effectiveness and safety of meshes??

P l i P l Pelvic Prolapse Surgery???

Risk Factors for Mesh ComplicationsRisk Factors for Mesh ComplicationsppWhat Was Known When?What Was Known When?

1981: Pore size effects fibroblastic in1981: Pore size effects fibroblastic in--growth growth 1981: Pore size effects fibroblastic in1981: Pore size effects fibroblastic in growth growth (dogs)(dogs)1986: Polypropylene degrades in humans1986: Polypropylene degrades in humans1997 P i f th d ib d1997 P i f th d ib d1997: Pore size further described1997: Pore size further described1990’s: Mesh shrinkage 1990’s: Mesh shrinkage 2002: Mesh surface area related to complications2002: Mesh surface area related to complications2002: Mesh surface area related to complications2002: Mesh surface area related to complications2003: Stiffness of the mesh influences erosion2003: Stiffness of the mesh influences erosionWhy haven’t manufacturers developed meshes to Why haven’t manufacturers developed meshes to t k th f t i t t?t k th f t i t t?take these factors into account?take these factors into account?

White RA et al. Biomaterials 1981;2:171-6; Amid P. Hernia 1997;1:15-21; Klinge U, et al. Eur J Surg 1998;164:965-9; Klinge U, et al. J Biomed Mat Res 2002;63:765-71; Dietz HP, et al. Int Urogynecol J 2003;14:239-43.

The Path to Erosion and Other Mesh Complications↓↓

High Responder↓

Mesh Insertion←Contaminated Vaginag↓

The Race for the Mesh Surface ____________________↓_____________________

↓ ↓Monofilament Multifilament

Large pore Small PoreLow Weight High WeightLow Weight High Weight

Smooth Surface Rough SurfaceSmall Surface area Large Surface Area

↓ ↓↓ ↓Host Defenses Win Bacteria Win

↓ ↓→→→→→→→→→→→→→ ↓←←←←←←←←←←↓

Acute Inflammatory Reaction →Immune Response

Chronic Inflammatory ReactionChronic Inflammatory Reaction↓

Macrophages Secrete Acidic Compounds↓

Oxidation↓↓

Degradation→Brittleness↓ →>Surface area ↓ → Roughness↓ → Roughness

↓ ←←←←← →→→→→ ↓Absorbed Polypropylene Toxic Compounds

↓ ↓Immune Response?? Enhanced Inflammatory

True Rejection?? → ↓ ←←←← Reaction j ↓Mesh Shrinkage

Continued EnhancedContinued EnhancedInflammmatory Reaction

↓i f iErosion←←←←←Infection

Surgeon: ↓Thin or ↓↓Punctured Vagina→→→→

↓WickingWicking

↓Total Mesh Infection

The Ideal MeshThe Ideal MeshThe Ideal MeshThe Ideal Mesh

NonNon--reactive in tissuereactive in tissueNonNon reactive in tissuereactive in tissueRepels bacterial adherenceRepels bacterial adherenceN d d ti t i l t tiN d d ti t i l t tiNo degradation post implantationNo degradation post implantationNo antigenicityNo antigenicityNo scar tissue stimulationNo scar tissue stimulationNo shrinkage over timeNo shrinkage over timeNo shrinkage over timeNo shrinkage over timeNo erosion or migrationNo erosion or migration

Proposed Simple MeshProposed Simple MeshProposed Simple MeshProposed Simple Mesh

W ld dNo Weldedjoints

No interstices

N l

Mono-fil t

No placefor bacteriato hide

filament

But, it stillhas a Flexiblehas a surfacearea forb t i l

Light weightbacterial

adherence

weight

Proposed Simple MeshProposed Simple MeshProposed Simple MeshProposed Simple Mesh

SIMPLE COMPLEX

Let’s continue to look forLet’s continue to look forLet’s continue to look for Let’s continue to look for the perfect mesh, butthe perfect mesh, but------the perfect mesh, butthe perfect mesh, butLet’s discover it using Let’s discover it using

evidence based medicineevidence based medicinehhOtherwise, Otherwise,

how will we know when we how will we know when we how will we know when we how will we know when we have found it?have found it?

Don’t ConfuseDon’t ConfuseDon t Confuse Don t Confuse Medical Marketing Medical Marketing gg

with Science!with Science!

Require Evidence Based Medicine!Require Evidence Based Medicine!

Thank You!!