PERMACOL IMPLANT EVIDENCE SUMMARY

Transcription

1 PERMACOL IMPLANT EVIDENCE SUMMARY Use of Permacol surgical implant in a contaminated or infected field may lead to a weakening or breakdown of the implant. Treat any existing or suspected infection according to accepted medical practice before implanting the device.

2 CONTENT OUTLINE Abdominal wall reconstruction Consequence of postoperative infections Use of biologic grafts Permacol : Production specifications Permacol : The evidence Other xenografts: Overall evidence Future evidence

3 ABDOMINAL WALL RECONSTRUCTION Repair of abdominal wall defects may be needed during: Complex abdominal surgeries Large ventral/incisional hernia

4 COMPLEX AND CHALLENGING SURGERY Common patient characteristics: One or more comorbidities Clean/contaminated, contaminated or dirty surgical field High risk of postoperative infections Requiring component separation

5 CONSEQUENCE OF POSTOPERATIVE INFECTIONS Recurrence Serious wound or mesh infection Mesh explantation Other serious complications

6 USE OF BIOLOGIC GRAFT Clinical argument Similar characteristics to synthetic meshes: - Enough mechanical strength - Supports tissue ingrowth and regeneration Reduces foreign-body inflammatory response Allows neovascularization

7 USE OF BIOLOGIC GRAFT Economic argument Reduces number and time of operation Shortens hospital stay Reduces costs for further operation and care High cost for graft offset by shortened hospital stay and reduced risk of re-operation

8 PERMACOL SURGICAL IMPLANT Made of >99% collagen Natural cross-links exist in collagen for strength The addition of chemical cross-links provide collagen with added strength and protection in contaminated/infected sites Chemical cross-links modify 2 of 1000 amino acids (0.2%) in a single collagen molecule of Permacol Permacol Surgical Implant

9 PERMACOL SURGICAL IMPACT ASSESSING THE CLINICAL EVIDENCE Non-systematic literature searches were performed using PubMed, MEDLINE, Embase and the Cochrane Library in July 2013 Evidence is limited to clinical studies published in peer-reviewed journals in English during the period The level of the evidence is assessed according to Oxford Centre for Evidence-Based Medicine, 2011 version The quality of the evidence is assessed using Modified Methodological Index of Non-Randomised Studies (MINORS) scores. Studies with a MINORS score lower than 8 have not been included If the information is available, the author-assessed surgical wound classification is presented

10 LEVELS OF EVIDENCE Oxford Centre for Evidence-Based Medicine, 2011 version Question: Does this intervention help? (treatment benefits) Level * Level 1 Level 2 Description Systematic review of randomized trials, or n-of-1 trials Randomized trial or observational study with dramatic effect Level 3 Non-randomized controlled cohort/follow-up study ** Level 4 Case-series, case-control studies, or historically controlled studies ** Level 5 Mechanism-based reasoning Evidence gradin *** Positive for Medtronic Permacol Surgical Implant, superior to the comparator, or equivalent to the comparator where effect is considered optimal Neutral for Medtronic Permacol Surgical Implant or comparable to the comparator Negative for Medtronic Permacol Surgical Implant, or the comparator shows superiority over Medtronic Permacol * Level may be downgraded on basis of study quality, imprecision, indirectness, because of inconsistency between studies, or because the absolute effect size is very small; Level may be upgraded if there is a large or very large effect size. ** A systematic review is generally better than an individual study. *** For Medtronic Internal use only Source: Oxford Centre for Evidence-Based Medicine.

11 MODIFIED METHODOLOGICAL INDEX OF NON-RANDOMISED STUDIES (MINORS) Item Criteria Option Score 1 A clearly stated aim Partially reported, no clear aim Clear aim 2 Minimum of 5 patients included No Yes 3 Inclusion of consecutive patients Patients in a certain time period Consecutive patients + characteristics 4 Diagnostic modality of follow-up /unclear/telephone used Clinical examination Clinical examination + CT/Ultrasound 5 Surgical methods (i.e., anatomic placement of prosthesis, surgical technique, bridge/ reinforcement used) Incomplete Reported clearly, appropriate to aim 6 Endpoints clearly stated in methods section /unclear Stated but inadequate Clearly stated 7 Endpoints appropriate to aim Recurrences only Recurrences and postoperative complication Source: Slater et al. Am J Surg 2013;205: Maximum score

12 SURGICAL WOUND CLASSIFICATION Class Class I. Clean Class II. Clean-contaminated Class III. Contaminated Class IV. Dirty Description An uninfected operative wound in which no inflammation is encountered and the respiratory, alimentary, genital, or uninfected urinary tract is not entered. In addition, clean wounds are primarily closed and, if necessary, drained with closed drainage. Operative incisional wounds that follow nonpenetrating (blunt) trauma should be included in this category if they meet the criteria. An operative wound in which the respiratory, alimentary, genital, or urinary tracts are entered under controlled conditions and without unusual contamination. Specifically, operations involving the biliary tract, appendix, vagina, and oropharynx are included in this category, provided no evidence of infection or major break in technique is encountered. Open, fresh, accidental wounds. In addition, operations with major breaks in sterile technique (e.g., open cardiac massage) or gross spillage from the gastrointestinal tract, and incisions in which acute, nonpurulent inflammation is encountered are included in this category. Old traumatic wounds with retained devitalized tissue and those that involve existing clinical infection or perforated viscera. This definition suggests that the organisms causing postoperative infection were present in the operative field before the operation. Source: Mangram AJ et al. Guideline for Prevention of Surgical Site Infection, Centers for Disease Control and Prevention (CDC)

13 OUTCOMES: CLINICAL EVIDENCE OVERVIEW Outcomes Evidence Level MINORS * Evidence Grading Recurrence Infections Other complications Pain 4 13 Adhesions 5 n/a Implant degradation 5 n/a Inflammatory response 5 n/a Tissue integration 5 n/a Neovascularization 5 n/a Evidence gradin ** Amount of evidence Positive for Medtronic Permacol Surgical Implant, superior to the 5 studies comparator, or equivalent to the comparator where effect is considered optimal 1 study Neutral for Medtronic Permacol Surgical Implant or comparable to the comparator Negative for Medtronic Permacol Surgical Implant, or the comparator shows superiority over Medtronic Permacol * The maximum possible MINORS score is 14 ** For Medtronic Internal use only

14 OUTCOME: RECURRENCE Level MINORS Grading Mesh Title 4 11/14 Permacol Use of porcine dermal collagen graft (Permacol) for hernia repair in contaminated fields 4 11/14 Permacol, Composix Cross-linked acellular porcine dermal collagen implant in laparoscopic ventral hernia repair: case-controlled study of operative variables and early complications 4 13/14 Permacol Evaluation of porcine dermal collagen (Permacol) used in abdominal wall reconstruction 4 10/14 Permacol Porcine dermal collagen (Permacol) for abdominal wall reconstruction 4 9/14 Permacol, Alloderm, Goretex, Vicryl, others Synthetic and biologic mesh in component separation: a 10-year single institute review 4 12/14 Permacol Abdominal wall reconstruction with dual layer cross-linked porcine dermal xenograft: the pork sandwich" herniorraphy 4 12/14 Permacol Experience with porcine acellular dermal collagen implant in one-stage tension-free reconstruction of acute and chronic abdominal wall defects 4 8/14 Permacol Initial evaluation of Permacol bioprosthesis for the repair of complex incisional and parastomal hernias 4 13/14 Permacol + Premilene Initial experience of double-layer tension free reconstruction of abdominal wall defects with porcine acellular dermal collagen implant and polypropylene mesh

15 OUTCOME: INFECTIONS Level MINORS Grading Mesh Title 4 11/14 Permacol Use of porcine dermal collagen graft (Permacol) for hernia repair in contaminated fields 4 11/14 Permacol, Composix Cross-linked acellular porcine dermal collagen implant in laparoscopic ventral hernia repair: case-controlled study of operative variables and early complications 4 13/14 Permacol Evaluation of porcine dermal collagen (Permacol) used in abdominal wall reconstruction 4 10/14 Permacol Porcine dermal collagen (Permacol) for abdominal wall reconstruction 4 12/14 Permacol Abdominal wall reconstruction with dual layer cross-linked porcine dermal xenograft: the pork sandwich" herniorraphy 4 12/14 Permacol Experience with porcine acellular dermal collagen implant in one-stage tension-free reconstruction of acute and chronic abdominal wall defects 4 8/14 Permacol Initial evaluation of Permacol bioprosthesis for the repair of complex incisional and parastomal hernias 4 13/14 Permacol + Premilene Initial experience of double-layer tension free reconstruction of abdominal wall defects with porcine acellular dermal collagen implant and polypropylene mesh 5 n/a Permacol Human in vivo cellular response to a cross-linked acellular collagen implant

16 OUTCOME: OTHER COMPLICATIONS Level MINORS Grading Mesh Title 4 11/14 Permacol Use of porcine dermal collagen graft (Permacol) for hernia repair in contaminated fields 4 11/14 Permacol, Composix Cross-linked acellular porcine dermal collagen implant in laparoscopic ventral hernia repair: case-controlled study of operative variables and early complications 4 13/14 Permacol Evaluation of porcine dermal collagen (Permacol) used in abdominal wall reconstruction 4 10/14 Permacol Porcine dermal collagen (Permacol) for abdominal wall reconstruction 4 12/14 Permacol Abdominal wall reconstruction with dual layer cross-linked porcine dermal xenograft: the pork sandwich" herniorraphy 4 12/14 Permacol Experience with porcine acellular dermal collagen implant in one-stage tension-free reconstruction of acute and chronic abdominal wall defects 4 8/14 Permacol Initial evaluation of Permacol bioprosthesis for the repair of complex incisional and parastomal hernias 4 13/14 Permacol + Premilene Initial experience of double-layer tension free reconstruction of abdominal wall defects with porcine acellular dermal collagen implant and polypropylene mesh

17 OUTCOME: OTHER OUTCOMES Pain Level MINORS Grading Mesh Title 4 13/14 Permacol + Premilene Initial experience of double-layer tension free reconstruction of abdominal wall defects with porcine acellulardermal collagen implant and polypropylene mesh Adhesion Level MINORS Grading Mesh Title 5 n/a Permacol Human in vivo cellular response to a cross-linked acellular collagen implant Implant degradation Level MINORS Grading Mesh Title 5 n/a Permacol Human in vivo cellular response to a cross-linked acellular collagen implant Inflammatory response Level MINORS Grading Mesh Title 5 n/a Permacol Human in vivo cellular response to a cross-linked acellular collagen implant Tissue integration Level MINORS Grading Mesh Title 5 n/a Permacol Human in vivo cellular response to a cross-linked acellular collagen implant Neovascularization Level MINORS Grading Mesh Title 5 n/a Permacol Human in vivo cellular response to a cross-linked acellular collagen implant

18 EVIDENCE BRIEF: CATENA ET AL Title Use of porcine dermal collagen graft (Permacol) for hernia repair in contaminated fields No. of patients 7 Country Italy Type of surgery Repair of complicated incisional hernia Evidence level 4 MINORS score 11/14 (79%) Recurrence Infections Other complications Previous surgery Defect size Contamination Comorbidities Implant Major abdominal surgery or hysterectomy to cm Contaminated fields in all patients COPD, IHD, previous DVT, lymphoma; others not reported Permacol Implant position Underlay (71%), onlay (29%) Follow-up period Mean 11.1 months (range 7-18 months) Publication Hernia 2007;11:57-60 Authors conclusions: Use of Permacol is potentially safe and efficient in contaminated fields Outcomes Recurrence Complications Infections Pain No recurrence 14.2% (n=1) had acute postoperative pneumonia No wound infection COPD: Chronic obstructive pulmonary disease, IDH: Ischemic heart disease, DVT: Deep vein thrombosis.

19 EVIDENCE BRIEF: COBB & SHAFFER 2005 Title Cross-linked acellular porcine dermal collagen implant in laparoscopic ventral hernia repair: case-controlled study of operative variables and early complications No. of patients 139 Country USA Evidence level 4 MINORS score 11/14 (79%) Recurrence Infections Other complications Type of surgery Previous surgery Defect size Contamination Comorbidities Implant Implant position Follow-up period Publication Outcomes Recurrence Complications Infections Pain Repair of incisional hernia and primary ventral hernia Wound contamination in 7.2% patients (n=4) in the Permacol group Mean BMI kg/m 2 ; others not reported Permacol (n=55) vs Composix (n=84, historical controls) Laparoscopically inserted Permacol group: 14 months; Composix group: 31 months (averages) Int Surg 2005;90:S24-9 Permacol group: 6.6% (n=4); Composix group: 1.2% (n=1); no significant difference between groups Permacol group: 13.3% (n=8); Composix group: 13.1% (n=11) Wound infections in Permacol group: 3.3% (n=2, one requiring mesh removal); Composixgroup: 2.4% (n=2, both requiring mesh removal) Authors conclusions: Permacol is safe for use in laparoscopic ventral hernia repair

20 EVIDENCE BRIEF: HSU ET AL Title Evaluation of porcine dermal collagen (Permacol) used in abdominal wall reconstruction No. of patients 28 Country USA Type of surgery Repair of abdominal wall hernia Evidence level 4 MINORS score 13/14 (93%) Recurrence Infections Other complications Previous surgery Laparotomy incision or open abdomen after trauma Defect size Mean 150 cm 2 (range cm 2 ) Contamination Comorbidities Implant Implant position Mean BMI 34 kg/m 2, BMI > 30 kg/m 2 (57%), hypertension, diabetes Permacol Underlay Follow-up period Mean 16 months Publication J Plast Reconstr Aesthet Surg 2009;62: Outcomes Authors conclusions: Permacol can be successfully used in the reconstruction of both small and large ventral hernias Recurrence Complications Infections Pain P10.7% (n=3, one requiring re-operation) 7.1% (n=2) had minor complications (seroma plus cellulitis; localized wound infection); 14.3% (n=4, none requiring implant removal) developed a chronic, non-infected fluid collection

21 EVIDENCE BRIEF: PARKER ET AL Title Porcine dermal collagen (Permacol) for abdominal wall reconstruction No. of patients 9 Country USA Type of surgery Abdominal wall reconstruction Evidence level 4 MINORS score 10/14 (71%) Recurrence Infections Other complications Previous surgery Defect size Contamination 56% (n=5) had previous incisional hernia repair Class II, III or IV contamination in 56% (n=5) Comorbidities Obesity (56%), diabetes (44%), hypertension (44%), COPD (22%), smoking (33%), metastatic cancer (22%) Implant Permacol Implant position Underlay Follow-up period Mean 18.2 months Publication Curr Surg 2006;63:255-8 Outcomes Authors conclusions: Permacol is a safe and acceptable alternative to synthetic mesh in repair of complex abdominal wall defects Recurrence Complications Infections Pain 11% (n=1) following mesh removal after wound infection 22% (n=2): exposure of graft due to skin separation plus 1 death due to unrelated causes 11% (n=1) leading to mesh removal

22 EVIDENCE BRIEF: SAILES ET AL Title Synthetic and biologic mesh in component separation: a 10-year single institute review No. of patients 545 Country USA Type of surgery Abdominal wall reconstruction Evidence level 4 MINORS score 9/14 (64%) Recurrence Infections Other complications Previous surgery Defect size Contamination Comorbidities Implant In biologic mesh group: diabetes (17%), smoking (20%), others (age > 65 years, obesity) not specified Permacol (n=13), Alloderm (n=100), Goretex (n=80), Vicryl (n=51), other (n=76) Implant position All meshes implanted using component separation with onlay mesh Follow-up period Publication Ann Plast Surg 2010;64:696-8 Outcomes Authors conclusions: There was no statistical significance for recurrence with respect to the type of mesh used Recurrence Permacol group: 8% (n=1); Alloderm group: 19% (n=19); Goretex 35% (n=28), Vicryl 18% (n=9), other 21% (n=16) Complications Infections Pain Mesh-specific complication rates not reported Mesh-specific infection rates not reported

23 EVIDENCE BRIEF: SATTERWHITE ET AL Title Abdominal wall reconstruction with dual layer cross-linked porcine dermal xenograft: the pork sandwich" herniorraphy No. of patients 19 Country USA Type of surgery Repair of large ventral hernia Evidence level 4 MINORS score 12/14 (64%) Recurrence Infections Other complications Previous surgery Average of 2 previous abdominal operations Defect size Mean 321 cm 2 (range cm 2 ) Contamination Comorbidities Ostomy/enterotomy in 58% patients (n=11); enterocutaneous fistula in 26% (n=5) Obesity (n=9), smoking history (n=3), diabetes (n=2), chronic immunosuppression for transplantation (n=1), history of radiation (n=1) Implant Implant position Follow-up period Pork sandwich group: Permacol ; historical case-control group: various types of biologic (including Permacol ) and synthetic meshes Permacol pork sandwich group: one mesh underlay, one overlay to form the pork sandwich ; control group: underlay or onlay Permacol pork sandwich group: 11 months (range 1-33 months); control group: 15 months (1-71 months) Publication J Plast Reconstr Aesthet Surg 2012;65: Authors conclusions: Use of Permacol pork sandwich herniorraphy may be suitable for abdominal defects in patients with infection risk and comorbidities Outcomes Recurrence Complications Permacol pork sandwich group: no recurrences; control group: 19% (n=16), p=0.038 Complication rate (53%) and re-operation rate (36%) in the Permacol pork sandwich group did not differ significantly from those in the control group (64% and 25%, respectively). Infections Permacol pork sandwich group: 16% (n=3); control group: 27% (n=23) (p=not significant) Pain

24 EVIDENCE BRIEF: SHAIKH ET AL Title Experience with porcine acellular dermal collagen implant in one-stage tension-free reconstruction of acute and chronic abdominal wall defects No. of patients 20 Country Ireland Evidence level 4 MINORS score 12/14 (86%) Recurrence Infections Other complications Type of surgery Previous surgery Repair of chronic/acute large incisional hernia or abdominal wall defects (CAWD/AAWD) Not specified Defect size Median 180 cm 2 (range cm 2 ) Contamination Not specified Comorbidities Obesity (15%), diabetes (15%), Crohn s disease (5%), COPD (5%) Implant Permacol Implant position Follow-up period Underlay Median 18 months (range 6-36 months) Publication World J Surg 2007;31: Outcomes Recurrence Overall: 15% (n=3); CAWD group: 8% (n=1/12); AAWD group: 25% (n=2/8) Authors conclusions: Permacol is useful for reconstruction of large acute and chronic abdominal wall defects. Medium-term recurrence rate is comparable to that with synthetic mesh repairs Complications Infections 35% (n=7), plus 1 death from unrelated causes 10% (n=2) of AAWD group had wound infections Pain COPD: Chronic obstructive pulmonary disease

25 EVIDENCE BRIEF: LOGANATHAN ET AL Title Initial evaluation of Permacol bioprosthesis for the repair of complex incisional and parastomal hernias No. of patients 15 Country UK Type of surgery Repair of large, complex and contaminated hernias Evidence level 4 MINORS score 8/14 (57%) Recurrence Infections Other complications Previous surgery Defect size Contamination Comorbidities Implant Implant position Median 3 (range 1-9) major abdominal procedures Not specified Not specified; some patients had contaminated field Not specified Permacol Onlay or inlay Follow-up period Median 12 months (range 4-63 months) Publication Surgeon 2010;8:202-5 Outcomes Authors conclusions: Permacol appears resistant to infection and can be safely used for complex and contaminated hernia repair Recurrence Complications Infections 13% (n=2) 73% (n=11, none required mesh removal) 27% (n=4, none requiring mesh removal) had wound infections; 7% (n=1) each with an RTI or oral thrush Pain RTI: Respiratory tract infection

26 EVIDENCE BRIEF: SHAIKH ET AL Title Initial experience of double-layer tension free reconstruction of abdominal wall defects with porcine acellular dermal collagen implant and polypropylene mesh No. of patients 10 Country Ireland Type of surgery Repair of large abdominal wall incisional or umbilical hernias Previous surgery Not specified; primary repairs in 5; recurrent repairs in 5 Evidence level 4 MINORS score 13/14 (93%) Recurrence Infections Other complications Pain Defect size Contamination 75 cm2 Comorbidities 100% had comorbidities, including obesity (80%), diabetes (40%), cancer (20%), COPD (20%), IHD (20%), CCF (20%) Implant Permacol plus Premilene to form a double-layer Implant position Underlay (Permacol ) and onlay (Premilene ) Follow-up period Median 15.5 months (range 6-29 months) Publication Ir J Med Sci 2012;181:205-9 Outcomes Authors conclusions: The use of a double-layer of Permacol and Premilene in abdominal wall reconstruction is safe and effective. Recurrence Complications Infections Pain No recurrence 40% (n=4) 20% (n=2, none requiring mesh removal); 10% (n=1) LRTI No chronic pain reported on follow up COPD: Chronic obstructive pulmonary disease, IHD: Ischemic heart disease, CCF: Congestive cardiac failure. LRTI: Lower respiratory tract infection

27 EVIDENCE BRIEF: HAMMOND ET AL Title Initial evaluation of Permacol bioprosthesis for the repair of complex incisional and parastomal hernias No. of patients 15 Country UK Type of surgery Contamination Implant Implant position Follow-up period Prevention of parastomal hernia in patients undergoing loop stoma formation; later reversed in 12 Permacol Onlay (n=6) or sublay (n=9) Median 7 months (range 1-8 months) in 12 who underwent stoma reversal; 12 months in all patients Evidence level 4 MINORS score 13/14 (93%) Herniation Infection Adhesion Inflammatory response Implant degradation Tissue integration Neovascularization Publication Br J Surg. 2008;95(4): Outcomes Herniation Infections Adhesions Microscopic findings (from 11 of 12 explanted implants) 6.7% (n=1/15) 8% (n=1/12) developed infection requiring implant removal Adherence to bowel serosa was absent or limited Mild-to-moderate non-foreign body inflammatory response Minimal implant degradation No evidence of fibrosis or implant contraction Increased fibroblast integration and proliferation Increased synthesis of neo-extracellular matrix proteins Neovascularization at the periphery of the implant and via native pores Organized deposition of neocollagen Fibrovascular ingrowth * and extracellular matrix deposition were limited, but there was evidence that further ingrowth may occur with longer follow up *Attributed to the resistance of Permacol to matrix metalloproteinases as a result of cross-linking Authors conclusions: Permacol demonstrated excellent biocompatibility and resistance to degradation. However, fibrovascular ingrowth and extracellular matrix formation were limited. It has excellent potential for soft tissue reinforcement.

28 REFERENCES FOR PERMACOL SURGICAL IMPLANT 1. Catena F et al. Use of porcine dermal collagen graft (Permacol) for hernia repair in contaminated fields. Hernia. 2007;11(1): Cobb GA and Shaffer J. Cross-linked acellular porcine dermal collagen implant in laparoscopic ventral hernia repair: case-controlled study of operative variables and early complications. Int Surg. 2005;90(3 Suppl):S Hammond TM et al. Human in vivo cellular response to a cross-linked acellular collagen implant. Br J Surg. 2008;95(4): Hsu PW et al. Evaluation of porcine dermal collagen (Permacol) used in abdominal wall reconstruction. J Plast Reconstr Aesthet Surg. 2009;62(11): Loganathan A et al. Initial evaluation of Permacol bioprosthesis for the repair of complex incisional and parastomal hernias. Surgeon. 2010;8(4): Parker DM et al. Porcine dermal collagen (Permacol) for abdominal wall reconstruction. Curr Surg. 2006;63(4): Sailes FC et al. Synthetic and biological mesh in component separation: a 10-year single institution review. Ann Plast Surg. 2010;64(5): Satterwhite TS et al. Abdominal wall reconstruction with dual layer cross-linked porcine dermal xenograft: the "Pork Sandwich herniorraphy. J Plast Reconstr Aesthet Surg. 2012;65(3): Shaikh FM et al. Experience with porcine acellular dermal collagen implant in one-stage tension-free reconstruction of acute and chronic abdominal wall defects. World J Surg. 2007;31(10): ; discussion , Shaikh FM et al. Initial experience of double-layer tension free reconstruction of abdominal wall defects with porcine acellular dermal collagen implant and polypropylene mesh. Ir J Med Sci. 2012;181(2): Back to Permacol Surgical Implant clinical evidence overview

29 OTHER XENOGRAFTS USED FOR ABDOMINAL WALL RECONSTRUCTION Type Product name Manufacturer Cross-linked porcine dermal collagen CollaMend FM Implants Bard Non-cross-linked porcine dermal collagen Porcine small intestine submucosa Strattice Reconstructive Tissue Matrix XenMatrix Surgical Graft Biodesign (Surgisis ) LifeCell Bard Cook Medical Bovine dermal SurgiMend TEI Biosciences collagen * Bovine pericardium * Peri-Guard Repair Patch Synovis Veritas Collagen Matrix Tutomesh Baxter Tutogen * Not enough clinical evidence available to make assessment

30 OUTCOMES WITH OTHER XENOGRAFTS USED FOR ABDOMINAL WALL RECONSTRUCTION Cross-linked porcine dermal collagen: CollaMend Outcomes Assessment Recurrence Recurrence rates ranged from 0 to 44% (n=8/18); recurrences all seen in cases where mesh was placed using the interpositional technique; no recurrences seen when intraperitoneal mesh was reinforced with an onlay synthetic patch, or was placed onlay or inlay Infections Infection rates ranged from 22% to 40% Other complications References Rates of seroma/hematoma development ranged from 17% to 33%

31 OUTCOMES WITH OTHER XENOGRAFTS FOR ABDOMINAL WALL RECONSTRUCTION Non-cross-linked porcine dermal collagen: Strattice Outcomes Assessment Recurrence Recurrence rates ranged from 0% to 90%. Higher recurrence rates achieved if wound was bridged by the biologic graft. Infections Infection rates ranged from 0% to 54% Other complications References Complication rates ranged from 22% to 29% Non-cross-linked porcine dermal collagen: XenMatrix Outcomes Assessment Recurrence Recurrence rate ranged from 5-8% Infections Infection rates ranged from 0 to 8% Other complications Rates of seroma development ranged from 0% to 42% References

32 OUTCOMES WITH OTHER XENOGRAFTS FOR ABDOMINAL WALL RECONSTRUCTION Porcine small intestine submucosa: Biodesign (Surgisis ) Outcomes Assessment Recurrence Recurrence rates ranged from 0 to 30% Infections Infection rates ranged from 0 to 40% Other complications Complication rates ranged from 10% to 42% References

33 REFERENCES FOR OTHER XENOGRAFTS Cross-linked porcine dermal collagen 1. Chavarriaga LF et al. Management of complex abdominal wall defects using acellular porcine dermal collagen. Am Surg. 2010;76(1): Nasajpour H, LeBlanc KA, Steele MH. Complex hernia repair using component separation technique paired with intraperitoneal acellular porcine dermis and synthetic mesh overlay. Ann Plast Surg. 2011;66(3): Non-cross-linked porcine dermal collagen: Strattice 1. Butler CE and Campbell KT. Minimally invasive component separation with inlay bioprosthetic mesh (MICSIB) for complex abdominal wall reconstruction. Plast Reconstr Surg. 2011;128(3): Itani KM et al. Prospective study of single-stage repair of contaminated hernias using a biologic porcine tissue matrix: the RICH Study. Surgery. 2012;152(3): Patel KM et al. The use of porcine acellular dermal matrix in a bridge technique for complex abdominal wall reconstruction: an outcome analysis. Am J Surg. 2013;205(2): Rosen MJ et al. A novel approach for the simultaneous repair of large midline incisional and parastomal hernias with biological mesh and retrorectus reconstruction. Am J Surg. 2010;199(3):416-20; discussion Shah BC et al. Not all biologics are equal! Hernia. 2011;15(2): Singh DP et al. A modified approach to component separation using biologic graft as a load-sharing onlay reinforcement for the repair of complex ventral hernia. Surg Innov. 2014;21(2):

34 REFERENCES FOR OTHER XENOGRAFTS Non-cross-linked porcine dermal collagen: XenMatrix 1. Alicuben ET and Demeester SR. Onlay ventral hernia repairs using porcine non-cross-linked dermal biologic mesh. Hernia. 2013; [Epub ahead of print] 2. Byrnes MC et al. Repair of high-risk incisional hernias and traumatic abdominal wall defects with porcine mesh. Am Surg. 2011;77(2): Diaz-Siso JR et al. Abdominal wall reconstruction using a non-cross-linked porcine dermal scaffold: a follow-up study. Hernia. 2013;17(1): Pomahac B and Aflaki P. Use of a non-cross-linked porcine dermal scaffold in abdominal wall reconstruction. Am J Surg. 2010;199(1): Rosen MJ et al. A novel approach for the simultaneous repair of large midline incisional and parastomal hernias with biological mesh and retrorectus reconstruction. Am J Surg. 2010;199(3):416-20; discussion Porcine small intestine submucosa 1. Eid GM et al. Repair of ventral hernias in morbidly obese patients undergoing laparoscopic gastric bypass should not be deferred. Surg Endosc. 2004;18(2): Gupta A et al. Ventral herniorrhaphy: experience with two different biosynthetic mesh materials, Surgisis and Alloderm. Hernia. 2006;10(5): Helton WS et al. Short-term outcomes with small intestinal submucosa for ventral abdominal hernia. Arch Surg. 2005;140(6):549-60; discussion Ueno T, Pickett LC, de la Fuente SG, Lawson DC, Pappas TN. Clinical application of porcine small intestinal submucosa in the management of infected or potentially contaminated abdominal defects. J Gastrointest Surg. 2004;8(1):

35 FUTURE REFERENCE Ongoing and recently completed clinical trials registered at ClinicalTrials.gov NCT ID Title Device Sponsors Completion NCT Veritas in Non-Bridging Ventral Hernia Repair (VIBE) Veritas Collagen Matrix NCT NCT NCT NCT NCT ENHANCE: A Prospective EvaluatioN of Permacol in the Repair of Complex AbdomiNal Wall CasEs Prospective Trial Comparing the Performance Profiles of Two Non-Cross-Linked Porcine Dermal Matrices in Abdominal Wall Reconstruction Observational Study to Evaluate Ventral Incisional Hernia Repair Using a Biologic Mesh (Cook Biodesign) Multi-Center Study To Examine The Use Of Flex HD And Strattice In The Repair Of Large Abdominal Wall Hernias Abdominal Wall Repair With Strattice in Germany: a Cohort Study (BASE cohort) Permacol Biological Implant Strattice; XenMatrix Biodesign mesh Flex HD ; Strattice Strattice biological mesh Synovis Surgical Innovations August 2017 Medtronic December 2016 Janis, Jeffrey E, MD Mount Sinai School of Medicine Musculoskeletal Transplant Foundation Erasmus Medical Center NCT The Permacol Dutch Cohort Study Permacol mesh Erasmus Medical Center November 2016 April 2016 July 2015 February 2015 May 2014

36 GENERAL REFERENCES 1. Balayssac D et al. Use of permacol in parietal and general surgery: a bibliographic review. Surg Innov. 2013;20(2): Centre for Evidence Based Medicine. OCEBM levels of evidence system. Available at 3. Mangram AJ et al. Guideline for Prevention of Surgical Site Infection, Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control. 1999;27(2):97-132; quiz 133-4; discussion Slater NJ et al. Biologic grafts for ventral hernia repair: a systematic review. Am J Surg. 2013;205(2):

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