ANNALS OF SURGERYVol. 237, No. 1, 123–128 © 2003 Lippincott Williams & Wilkins, Inc. Prevention of Adhesion to Prosthetic Mesh Comparison of Different Barriers Using an Incisional Hernia Model Martijne van ’t Riet, MD,* Peggy J. de Vos van Steenwijk, MD,* Fred Bonthuis, MD,* Richard L. Marquet, PhD,* Ewout W. Steyerberg, PhD,† Johannes Jeekel, PhD,* and H. Jaap Bonjer, PhD* Departments of *General Surgery and †Public Health, Erasmus University Medical Centre, Rotterdam-Dijkzigt, Rotterdam, The Netherlands Objective Results To assess whether use of antiadhesive liquids or coatings could prevent adhesion formation to prosthetic mesh. Intraperitoneal placement of polypropylene mesh was followed by bowel adhesions to the mesh in 50% of the cases. A mean of 74% of the mesh surface was covered by adhesions after 7 days, and 48% after 30 days. Administration of Sepracoat or Icodextrin solution had no influence on adhesion formation. Coated meshes (Sepramesh and Parietex composite mesh) had no bowel adhesions. Sepramesh was associated with a significant reduction of the mesh surface covered by adhesions after 7 and 30 days. Infection was more prevalent with Parietex composite mesh, with concurrent increased mesh surface covered by adhesions after 30 days (78%). Summary Background Data Incisional hernia repair frequently involves the use of prosthetic mesh. However, concern exists about development of adhesions between viscera and the mesh, predisposing to intestinal obstruction or enterocutaneous fistulas. Methods In 91 rats, a defect in the muscular abdominal wall was created, and mesh was fixed intraperitoneally to cover the defect. Rats were divided in five groups: polypropylene mesh only (control group), addition of Sepracoat or Icodextrin solution to polypropylene mesh, Sepramesh (polypropylene mesh with Seprafilm coating), and Parietex composite mesh (polyester mesh with collagen coating). Seven and 30 days postoperatively, adhesions were assessed and wound healing was studied by microscopy. Incisional hernias occur in 5% to 20% of patients after abdominal surgery.1– 4 In incisional hernia repair, the introduction of tension-free techniques by using prosthetic material has reduced recurrence rates from up to 50% to less than 24%.5–9 However, foreign materials, such as prosthetic mesh, represent a strong stimulus for the development of permanent adhesions.10 Particularly if the mesh is placed intraperitoneally, concern exists about development of adhesions between bowel and mesh. These adhesions can Correspondence: Prof. dr. H. J. Bonjer, Academic Hospital Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. E-mail:
[email protected] Accepted for publication April 2, 2002. Conclusions Sepramesh significantly reduced mesh surface covered by adhesions and prevented bowel adhesion to the mesh. Parietex composite mesh prevented bowel adhesions as well but increased infection rates in the current model. cause serious complications, such as intestinal obstruction and enterocutaneous fistulas.11–14 The aim of the present study was to assess whether adhesions due to intraperitoneal mesh can be prevented by the use of physical barriers that can be applied laparoscopically. For this purpose, we assessed if intraperitoneal administration of liquid physical barriers composed of hyaluronic acid (Sepracoat, HAL-C; Genzyme Corp., Cambridge, MA) or Icodextrin solution (Extraneal, Baxter Healthcare Inc.) could prevent adhesions to a polypropylene mesh without interfering with wound healing and tissue incorporation of the mesh. In addition, we studied the ability of specifically coated meshes, Sepramesh (Genzyme) and Parietex composite mesh (Sofradim, France), to prevent adhesions. 123 the defect was repaired with a polypropylene mesh (Prolene) measuring 2. and peritoneum was created. In all animals. Surg. relative humidity 50 – 60%. but adhesions were assessed after 30 days instead of 7 days. Infection. the mesh surface was divided into six sections. and Incorporation Seven or 30 days postoperatively. Experiments Experiment 1 In 20 rats. After that. NJ) measuring 2. extending caudal and lateral to the mesh.5 ⫻ 2. Ethicon). To prevent leakage of the liquid Icodextrin solution. The experimental protocol adhered to rules set by the Dutch Animal Experimentation Act and was approved by the Committee in Animal Research of the Erasmus University Rotterdam. Each section was subsequently subdivided in six fields.5-cm longitudinal full-thickness defect consisting of fascia. Figure 1.5% solution (Extraneal) intraperitoneally (n ⫽ 10). Ethicon Inc. the skin of the animals was additionally closed with Histoacryl glue. In group 1 (n ⫽ 10). Experiment 3 Thirty rats were randomly divided into three groups. Seven days postoperatively. Somerville.16 In all animals. After placement of the mesh. The surface of the mesh that was covered by bowel and/or omental adhesions was assessed (Fig. For this purpose. The experiments were performed in a validated rat model described by Alponat et al. ● January 2003 METHODS Animals Ninety-one male inbred rats of the Wistar strain (weight 250 –300 g) were obtained from Harlan (Zeist. Nonpowdered gloves were used routinely in the experimental procedure.04 mL xylazine (20 mg/mL). kept under standard laboratory conditions (temperature 20 –24°C. In all animals. Ethicon). The abdomen was shaved and cleaned with alcohol 70%.124 van ’t Riet and Others Ann.5 ⫻ 3. 12 hours light/12 hours dark).5 ⫻ 3.5 ⫻ 3. coated with hyaluronic acid and carboxymethylcellulose on the visceral side of the mesh (Sepramesh). The Netherlands) and water ad libitum. n ⫽ 10) and addition of 4 mL Sepracoat solution (n ⫽ 10) intraperitoneally. adhesions were scored.. the defect was repaired with a polyester mesh with a collagen coating on the visceral side (Parietex composite mesh) Meshes were fixed intraperitoneally with eight interrupted Prolene 5-0 sutures and the skin was closed with continuous 4-0 polyglactin suture (Vicryl. and for each field the percentage of the surface covered by adhesions was estimated. Density of adhesions was scored according to . The Netherlands). adhesions were scored. In group 3. n ⫽ 10) and addition of 4 mL Icodextrin 7. the rats were randomized between no additional treatment (control group.5 cm that was fixed intraperitoneally with eight interrupted Prolene 5-0 sutures. The presence of adhesions between bowel and the mesh was assessed. adhesions were scored. Operative Procedure Following initial sedation with ether. all rats were killed and underwent autopsy. the mesh was excised and both bowel and omental adhesions were sharply cut. muscle. Subsequently.5 cm. the skin was closed with continuous 4-0 polyglactin suture (Vicryl. each animal received an intraperitoneal injection of 0. Scoring of Adhesions. Experiment 2 In 20 rats. Seven days postoperatively. A median skin incision was created and the abdominal cavity was entered through a U-shaped incision. 1). They were bred under specific pathogen-free conditions. Experiment 4 Experiment 4 was identical to experiment 3. the skin was closed with continuous 4-0 polyglactin suture (Vicryl.15 mL ketamine (100 mg/mL) and 0. laparotomy was performed using a midline incision of 4 cm. and fed with laboratory diet (Hope Farms. Woerden. Skin flaps were raised and a standardized 1. In group 2 (n ⫽ 10) the defect was repaired with a polypropylene mesh. Dense bowel adhesion to the mesh.15 and Hooker et al. Seven days postoperatively. Ethicon). the rats were randomized between no additional treatment (control group. the defect of the abdominal wall was repaired with a polypropylene mesh (Prolene. For each rat it was documented whether bowel adhesions were present.5 cm that was fixed intraperitoneally with eight interrupted Prolene 5-0 sutures. the defect of the abdominal wall was repaired with a polypropylene mesh (Prolene) measuring 2. P ⬍ . P ⫽ . P ⫽ . 4): * P ⫽ . and neutrophils (grade 2 on the inflammation grading scale). compared to 57% of the animals with polypropylene mesh (P ⫽ .03 . plasma cells.01).02 NS . and neutrophils.04). With Parietex composite mesh. 88%). In case of interobserver variance.04 NS NS Mean % of Mesh Not Incorporated (range) 7% (0–40) 12% (0–30) 11% (0–55) 16% (0–50) 3% (0–30) 6% (0–20) 13% (0–10) 33% (10–60) 19% (0–40) 4% (0–20) P NS NS NS NS NS NS Infection 0 0 0 0 0 0 40% 0 14% 57% P NS NS NS . either (P ⫽ .17 No herniations of viscera between mesh and abdominal wall were seen. sections were cut at 4 to 6 m and stained with hematoxylin and eosin. plasma cells. the mean was scored. Two independent investigators.07) and did not prevent bowel adhesions to the mesh. 82%. Instillation of Icodextrin 7. in the Parietex composite group. In all animals. Histology Of each group. eosinophils.01. a mean surface of 74% to 88% of the mesh was covered by adhesions (Table 1). as well as after 30 days (25% vs. With polypropylene mesh. After routine tissue processing. A comparable reaction was found in the groups with the addition of Sepracoat or Icodextrin to a polypropylene mesh and in the . compared to the control group.16 Grade 1 on this scale represents a mild inflammatory reaction with giant cells. However.03 5/10 4/10 6/10 5/10 5/10 0/9 0/9 4/7 0/7 0/7 P NS NS . Histologic evaluation in each control group showed foreign body reaction with giant cells and increased admixed lymphocytes. occasional scattered lymphocytes. three meshes with the adjoining abdominal wall were fixed in 10% neutral buffered formalin for at least 1 hour. and incorporation of the mesh in the surrounding tissue and inflammatory reaction were assessed for each group. 237 ● No. the infection rate was 57% at 30 days postoperatively compared to 0% in the control group (P ⫽ .01 NS . there were no bowel adhesions to the mesh. § P ⫽ . adhesions of the omentum to the prosthetic mesh were seen to some extent. Grade 2 represents a moderate reaction with giant cells and increased admixed lymphocytes.02). the percentage of mesh surface covered by adhesions was higher in the Parietex composite group (78%) than in the control group (48%. of Rats With Bowel Adhesion . bowel adhesions to the mesh were seen in 50% to 60% of all animals. Exp. When Sepramesh was used. 48%. 74%. P ⫽ . In addition.02 Comparison of mean % of mesh surface covered by adhesions at 7 and 30 days postoperatively (experiment 3 vs. P ⫽ NS. Zu¨ hlke classification. Icodextrin solution had no influence on the formation of bowel adhesions to the mesh.04 .5% solution did not reduce the surface of the mesh that was covered by adhesions. The grade of inflammation was assessed using a semiquantitative scoring system. RESULTS Two animals died before the end of the experiment on postoperative days 4 and 5 of unknown causes (experiment 3).05 was considered statistically significant. Further. 1 2 3 4 125 ADHESION FORMATION AND MESH INCORPORATION Group n Mean % of Mesh Surface Covered by Adhesions (range) Control Sepracoat Control Icodextrin Control Sepramesh Parietex Control Sepramesh Parietex 10 10 10 10 10 9 9 7 7 7 82% (56–99) 68% (42–86) 88% (72–100) 90% (55–100) 74% (27–94) 55% (8–78) 63% (3–100) 48% (22–56)* 25% (0–53)§ 78% (3–100)& P No. eosinophils. 1 Table 1.03). Instillation of Sepracoat solution in the peritoneal cavity did not significantly reduce the surface of the polypropylene mesh that was covered by adhesions (68% vs.03). a significant reduction in the mean percentage of mesh surface covered by adhesions was found after 7 days (55% vs. Grade 3 represents a severe inflammatory reaction with microabscesses present.04).02. performed scoring of adhesions and incorporation. These adhesions could be lysed only by sharp dissection (Zu¨ hlke classification 3). who were unaware of the group assignment of the rats. In addition. P ⫽ . Sections were microscopically studied.07 NS . either (90% vs. none of the animals with Sepramesh developed adhesions between bowel and the mesh. Statistical Analysis Statistical analysis was performed using the Mann-Whitney test for independent samples.Prevention of Adhesion to Prosthetic Mesh Vol. and plasma cells. the inflammation grading scale. Incorporation of the prosthesis in the abdominal wall was scored by dividing the circumference of the mesh into 10 segments and subsequently determining the number of segments in which the mesh was not incorporated in the abdominal wall.17 Infection was defined as pus coming from the mesh and wound. After 7 days. DISCUSSION The reduction of recurrence rates following reinforcement of the abdominal wall by mesh in incisional hernia has promoted the use of mesh. group with Sepramesh (Fig. as was found in the present study (experiment 4 vs. in the group with Parietex composite mesh.9 Polypropylene is most commonly used because it is easy to handle and relatively low in cost. 2). Surg.23. Because polypropylene causes a pronounced and persistent inflammatory reaction. and 3). However. ● January 2003 Figure 2. polypropylene causes a strong stimulus for the formation of adhesions. the mesh is well incorporated in the surrounding tissue of the abdominal wall. and Parietex composite mesh (C).25 With time. which results in increased deposition of fibrin matrix. This inhibition is followed by reduced fibrinolysis.22 Surgical trauma and foreign body reaction inhibit plasminogen activator activity. the extent of adhesions decreases by approximately 30%.21. 2. Incorporation of the mesh was similar in all study groups. experiments 1. with the presence of many admixed inflammatory cells and microabscesses (grade 3 on the inflammation grading scale).26 . Light microscopy of histology 7 days postoperatively with polypropylene mesh (A). However. a more severe inflammatory reaction was found. Sepramesh (B).18 –20 Adhesion formation is part of the normal healing process and is observed following 90% to 100% of all abdominal surgical procedures.24 The fibrin matrix gradually matures into an organized fibrous adhesion over the course of approximately 5 days. for the same reason.126 van ’t Riet and Others Ann. Verco et al. and glycerol.11 In conclusion. After 30 days. Sepramesh is composed of a polypropylene mesh that is coated with a bioresorbable membrane of hyaluronate and carboxymethylcellulose. it is supposed to separate damaged surfaces while postsurgical regeneration takes place. With infection and increased inflammatory reaction. although the difference was not statistically significant due to limited sample size. intra-abdominal residence time might be an important factor and may have to exceed at least 7 days. In a rat and rabbit model. 2. adhesion formation in the present study was evaluated after 7 days. polyethylene glycol.33 However. Parietex composite mesh was more easily infected than the other meshes and showed a stronger inflammatory response. The soluble form of Seprafilm (Sepracoat) would be easier to apply laparoscopically. Sepracoat persists at its site of application for only approximately 24 hours. The aim of the protective layer is to provide sufficient separation between the mesh and viscera while regeneration takes place without impeding tissue ingrowth of the mesh on the other side. but it did not reduce adhesions in the present study. synovial fluid. Through the attraction of fluid into the abdominal cavity. Fascia closure after midline laparotomy: results of a randomized trial.18. Hyaluronic acid is a glycosaminoglycan that is naturally found in the human body in connective tissue. Coated Meshes Recently.31 Thus. Liquid Antiadhesive Sepracoat is a viscous solution composed of 0. Van Vroonhoven TJMV. The Parietex composite mesh is a polyester mesh coated with an absorbable and hydrophilic film on the visceral side.4% hyaluronic acid in phosphate-buffered saline. the hydrophilic film provided significant protection against bowel adhesions after 7 days.29 In contrast to the present study. the intraabdominal amylase concentration is higher than in the rabbit. adhesion formation was also assessed after 30 days to evaluate the antiadhesive effect after resolution of the coating. References 1. which are bonded by polygalactide/polyglycolide.18. Icodextrin is metabolized by amylase to oligosaccharides and remains in the human abdominal cavity for at least 3 to 4 days. In addition. In the experiments with the coated meshes. in the current study. As was shown in the present study. Mudge M. concurrent increase of the surface of the mesh that was covered by adhesions was seen. Br J Surg 1987. The Sepracoat solution coats tissues with a temporary protective layer and is completely resorbed from the abdomen within 5 days.16. Hughes LE.33 Within 3 weeks the film is completely resorbed and a new peritoneal covering is formed over the mesh. have been introduced in surgery. coated meshes. and after 7 days no new adhesions are formed.27 Therefore.33 In the present study. a bioresorbable membrane of hyaluronate and carboxymethylcellulose (Seprafilm) has been reported to diminish adhesion formation significantly.28 After gynecologic surgery without a mesh. which may lead to a shorter intraperitoneal residence time of Icodextrin in the rat. with a protective layer on the visceral side of the mesh. Sepracoat was found to lessen intra-abdominal adhesion formation.28 In the present study. Sepramesh significantly reduced adhesion formation to the mesh after 7 days as well as after 30 days. Wissing JC. The film is composed of a solution of oxidized bovine atelocollagen type I. Sepramesh significantly reduced adhesion formation and prevented bowel adhesion to the mesh in the early postoperative period without interfering with wound healing and tissue incorporation of the mesh. Icodextrin induces ultrafiltration through colloid osmosis. A stronger inflammatory reaction with an increased incidence of infection and formation of enterocutaneous fistulas (16%) with the use of polyester mesh was also found in a clinical study by Leber et al. this membrane is not applicable in laparoscopic incisional hernia repair because of technical difficulties with the introduction and positioning of the sticky membrane. et al. Addition of liquid physical barriers such as Sepracoat or Icodextrin did not prevent adhesion of omentum or bowel to a polypropylene mesh. reported fewer adhesions after administration of Icodextrin in a uterine horn model in rabbits. Although iso-osmolar. in which we found no effect of Icodextrin on adhesion formation. Eeftinck Schattenkerk M. Icodextrin is a biodegradable glucose polymer solution that has been registered for peritoneal dialysis. Reduction of adhesions with the use of Parietex composite mesh was also found by Mutter et al.15. adhesion of viscera to the mesh was prevented after 7 days.30 In the rat. Br J Surg 1985. . 1 In the rat. the same trend was Prevention of Adhesion to Prosthetic Mesh 127 seen.Vol. 72:70 –71. Sepracoat did not significantly decrease the incidence of bowel or omental adhesions to the mesh. intra-abdominal adhesions form within 24 hours after the operation. The same trend was seen after 30 days.28. 237 ● No. Incisional hernia: a 10-year prospective study of incidence and attitudes. Future clinical studies are indicated to assess the promising results of coated meshes. thereby preventing formation of adhesions between surgical surfaces.32 However. Parietex composite mesh reduced bowel adhesions to the mesh as well but provoked a stronger inflammatory reaction in the current model. A possible explanation for this discrepancy between the results of Sepracoat and Seprafilm is the difference in intra-abdominal lifetime. while Seprafilm remains in place for at least 7 days. 74:738 –741. when the membrane was completely absorbed. although the difference was not statistically significant due to limited sample size. and vitreous humor. The antiadhesive membrane remains in place for up to 7 days31 and is subsequently absorbed. Moran BJ. 7. Reduction of de novo postsurgical adhesions by intraoperative precoating with Sepracoat (HAL-C) solution: a prospective. Greater risk of incisional hernia with morbidly obese than steroid dependent patients and low recurrence with prefascial polypropylene mesh. 24. Surgery 2000. Lemmen MH. 20. et al. Alexander AL. N Engl J Med 2000. 12. et al. Surg Forum 1969. Bonsack MS. Straub EM. 63:818 – 819. et al. an evaluation of risk factors. Wauters CC. 14. Unacceptable results of the Mayo procedure for repair of abdominal incisional hernias. Eur J Surg 1998. 3:95–101. 4. J Surg Res 1976. Garb JL. Harvey SB. Peers EM. Preclinical evaluation of a new composite mesh. Intraperitoneal fluid dynamics of 4% Icodextrin in non-ERSD patients. McGregor FH Jr. Can J Surg 1984. Paul A. 5. Hernia 2000. 2000. Taylor BM. Peters S. 10. . Incisional hernia recurrence following “vest over pants” or vertical Mayo repair of primary hernias of the midline. The role of fibrinolysis in the formation of postoperative adhesions. Mutter D. Hop WC. Klamer TW. Ellis H. Am J Surg 1996. Liakakos T. Buckman PD. Panagitidis H. Ann. Surgery 1999. Wound Rep Reg 1994. Ellis H. 31. Br J Surg 1994. Foreign material in postoperative adhesions. 27:159 –160. Engelberg M. Shapiro ME. van den Tol MP. 164:361–367. 21:148. randomized multicenter clinical study. 17. et al. Alponat A. Risberg B. 22. 171:80 – 84. Zachariou Z. Luijendijk RW. Fecal fistula: a late complication of Marlex mesh repair. Gewebereacktivitat Prosthetscher Materialien bei der Rekonstruktion von Defekten in der Chirurgie. Brown CB. Freeman JB. 30. et al. Risberg B. 66:904 –910. Am Surg 1997. Zager M. Parteka JJ. et al. Porter JM. et al. 27. Holmdahl L. et al. Reduction of adhesions after uterine myomectomy by Seprafilm membrane (HAL-F): a blinded prospective. Hufnagel HV. Prevention of adhesion formation with use of sodium hyaluronate-based bioresorbable membrane in a rat model of ventral hernia repair with polypropylene mesh . The concept of protected mesh to minimize adhesion formation in intraperitoneal abdominal wall reinforcement. 26. A comparison of prosthetic materials used to repair abdominal wall defects. Daum R. et al. Brown CB. Zu¨ hlke HV. et al. 21. 223:242–248. Healing of a gastrocutaneous fistula in the presence of Marlex. Arnold PB. De Wilt JHW. et al. Buckman RF. Fertil Steril 1998. 32. Prevention of adhesions by Seprafilm. Foresman PA. Macmillan JI. Adhesion formation and peritoneal healing on prosthetic materials. 176:228. Korenkov M. The Sepracoat Adhesion Study Group. Kellum JM Jr. The clinical significance of adhesions: Focus on intestinal obstruction. Hesselink VJ. 4:S3–9. Peers EM. Driman DK. Yavuz N. 33. Prevention of adhesions to polypropylene mesh in a traumatized bowel model. et al. Leber GE. 29. 19:S79. Luijendijk RW. Diamond MP. Hop WC. 191:131–136. Evaluation of resorbable barriers for preventing surgical adhesions. Surg. Verco SJ. Eur J Surg 1997. et al. 25. 15. et al.a randomized controlled study. Development of a novel glucose polymer solution (Icodextrin) for adhesion prevention: pre-clinical studies. J Am Coll Surg 2000. Incisional hernia recurrence. Karanikas I. Seprafilm reduces adhesions to polypropylene mesh. 577: 32–39. Clin Mater 1988. A comparison of suture repair with mesh repair for incisional hernia. Green CW. Moody DL. Baptista ML. Mullen DC. Thompson JN. 15:1764 –1772. Adhesion-related hospital readmissions after abdominal and pelvic surgery: a retrospective cohort study. ● January 2003 19. 18. Law NH. an absorbable adhesion barrier: an incisional hernia model in rats. 69:1067–1074. 73:157– 161. Pathophysiologie und Klassifikation von Adhesionen. Fertil Steril 2000. 21:62– 66. Delaney JP. Surgery 1983. Calton WC Jr. blinded. 16. 11. et al.128 van ’t Riet and Others 3. Jenkins SD. Adhesions: preventive strategies. Silen W. Gilbert JA. Peritoneal Dial Int 1999. Ellis H. Al-Jabreen M. de Lange DC. Diamond MP. Ann Surg 1996. Dis Col Rectum 1981. 94: 392–398. 6. 9. 81:248 –249. placebocontrolled multicenter study. 8. 24:53–54. et al. Luijendijk RW. A physiologic basis for the adhesion-free healing of deperitonealized surfaces.128:86 –92. Use of Marlex mesh in the repair of recurrent incisional hernia. et al. 125:211–216. Reines HD. 353:1476 –1480. Langenbecks Arch Chir Suppl II Verh Dtrsch Ges Chir 1990. 13. Cahalane MJ. Lorenz EMP. Eur J Surg 1997. 20:80 – 82. 10:392–398. Langenbecks Arch Chir (suppl II) 1995. 7:171– 176. Arch Surg 1998. randomized. Jamali FR. World J Surg 1997. Sugerman HJ. 577:5–9. Lakshminarasappa SR. et al. Surg Gynaecol Obstet 1993. 1337–1344. Lancet 1999. Hooker GD. 133:378 –382. Long-term complications associated with prosthetic repair of incisional hernias. 21:67–76. Luijendijk RW. 23. Fibrinolytic activity of mesothelial surfaces. Hum Reprod. Dinsmore RC. Abdominal incision: decision or indecision? Lancet 1989. et al. Kaufman Z. Fertil Steril 1996. 28. 345:1009 –1016.