Biologic Mesh
From SAGES Surgical Wiki
1 Introduction
2 Basic science of biologic meshes
3 Indications for use
3.1 Non contaminated setting
3.2 Bridging the gap
3.3 Reinforcement of the repair
3.4 Contaminated Setting
3.5 Prophylaxis during stoma creation
3.6 Hiatal Hernias
4 Conclusion
5 References


Introduction
Biologic mesh development resulted from a search for a biomaterial that could address the problems associated with permanent synthetic mesh, including chronic inflammation and foreign body reaction, stiffness and fibrosis, and mesh infection. Since the introduction of biologic mesh, the market has been rife with new biologic materials attached to largely unsupported claims of superiority and safety. With data comprised mainly from animal studies and Level III evidence, there has been little science regarding these materials, yet surgeons have been using these materials with increasing frequency driving a multi-million dollar market.

Basic science of biologic meshes
Most often derived from human or porcine dermis, these materials have been processed to acellular, porous extracellular matrix scaffolds of collagen and elastin. Some source growth factors remain and attract endothelial cells and subsequent fibroblasts into the mesh. These host cells release additional chemoattractants that signal the migration of other structural cells. The three-dimensional nature of the mesh and porosity allow cells to enter the mesh and adhere. What happens from there is a cycle of remodeling consisting of degradation of the biologic mesh and regeneration of the collagen scaffold with host tissue. The balance of this degradation and rebuilding process, and the speed with which it occurs, influences the ultimate strength and structure of the biologic mesh hernia repair.
The processing of the biologic mesh for production is by and large a proprietary procedure, making it difficult for surgeons to access information and answer several questions about the final products. These uncertain areas include decellularization, the sterilization process, the source of human dermis in terms of donor age and body part, and the crosslinking process. The cells are removed from the grafts in different ways: physical means such as dessication, chemical processes, or enzymatic reactions. Some of the products are terminally sterilized while others are not, resulting in variations in storage and pre-use hydration requirements. Sterilization options include gamma radiation, ethylene oxide, or hydrogen peroxide. Some companies instill chemicals, such as gluteraldehyde, into the biologic graft to induce additional crosslinking bonds in the graft to slow down the degradation process in the hope of leading to a stronger host collagen framework. However, this is a not a natural feature of the donor tissue and there is concern about the lack of remodeling in too heavily crosslinked grafts. This unintended feature could result in a poorly integrated graft and foreign body reaction, similar to some permanent synthetic meshes.
The advantage of crosslinked mesh versus non-crosslinked mesh remains a controversial area. Early investigation at Washington University presented at the 2009World Hernia Congress and the 2010 American Hernia Society Meeting showed increased stiffness for two crosslinked biologic mesh products (porcine dermis and bovine pericardium) compared to the non-crosslinked bovine pericardium mesh. 1-2 Greater cell infiltration was seen in the non-crosslinked mesh. Future investigation is warranted as to whether these characteristics are clinically important or if the crosslinked mesh poses an increased risk for infection by preventing collagen breakdown and macrophage migration.

Indications for use
The theoretical advantage of biologic mesh over synthetic mesh has appealed to surgeons, mostly in the United States. These meshes are not widely favored nor used in Europe and elsewhere due to the high cost of the biologic mesh over its cheaper and more widely applicable synthetic mesh counterpart. Over the last decade, surgeons have utilized biologic mesh in a variety of cases ranging from primary ventral and inguinal hernia repair in non-infected fields, recurrent hernias, reinforced hernia repair, hernia prophylaxis, and the most widely used application, hernia repair in the contaminated or potentially contaminated field.

Non contaminated setting
The use of biologic mesh in primary or recurrent ventral or inguinal herniorrhaphy in the noncontaminated and previously uninfected field is difficult to justify due to the high material cost without added benefit. There is very little data regarding the performance of biologic mesh in these settings.

Bridging the gap
The poor performance of the mesh in terms of laxity in a bridging repair makes this an unacceptable repair in the noncontaminated setting. Blatnik et al documented a recurrence rate of 80% for bridging repair with acellular dermal matrix at an average cost of $5,100 per patient, comparing the repair to an “expensive hernia sac.”3 The laxity associated with biologic mesh has been documented in other series.4

Reinforcement of the repair
The use of allograft or xenograft as reinforcement of a primary ventral hernia repair is felt to be a more sound approach. This fits with what we know of the science of biologic meshes in that placement in well-vascularized tissue is favorable for the ingrowth and remodeling process. Rosen’s group at Case Western investigated this and found a reduction in ventral hernia recurrence rate with a components separation midline repair reinforced with acellular dermal matrix (20%) compared to the 80% recurrence after bridging allograft repair.5

Contaminated Setting
The presence of contamination may limit the applicability of permanent synthetic mesh in some hernia repairs. Biologic mesh may be acceptable for this purpose or for placement in open wounds as a staged closure in complex abdominal wall reconstruction. There is limited data in both of these areas, with some noting a high risk of hernia recurrence and associated infection. The data is mostly limited to animal models and case series. 6,7 However, the lack of suitable alternatives has made biologic mesh attractive for contaminated field hernia repair.

Prophylaxis during stoma creation
The role of biologic mesh has been explored in prevention of parastomal hernias. An ongoing study of human dermis allograft placed at the time of construction of ileal conduits after cystectomy shows promising results with a decreased risk of hernia occurrence (30.4% v. 6.3%).8 Biologic mesh has also been used in the treatment of parastomal hernias where infection is a concern.9 With increasing reports of prophylactic synthetic mesh placement at the time of ostomy construction, the use of biologic mesh in this preventative setting may decline.

Hiatal Hernias
Biologic mesh has been utilized in the reinforcement of paraesophageal hernia repair. The randomized controlled trial of mesh repair for paraesophageal hernia lead by Oelschlager is the only Level I human study of biologic mesh.10 This study showed a decreased risk of hernia recurrence with mesh repair, from 24% to 9%. The recommendation for mesh reinforced hiatal repair is made with some caution; significant mesh complications, ranging from mesh erosion to esophageal stenosis and fibrosis, were documented in a follow-up study.11

Conclusion
In summary, biologic grafts represent a major advancement in complex hernia repair. Further investigation regarding the appropriate indications, performance of the grafts based on individual properties such as crosslinking, and potential complications is needed. Given the high cost of most of these materials and the limited available data, biologic mesh should be used judiciously and only when permanent synthetic mesh is inappropriate, such as in the contaminated field. The FDA reported complications of these materials warrant caution and sound surgical judgment.12,13




Biologic/bioresorbable graft comparison




Brand Name
Company
Type


AdditionallyCrosslinked?
Sterilized?

Alloderm®
LifeCell
Dermis
Human
No
No

Allomax™
CR Bard
Dermis
Human
No
Yes

Collamend™
CR Bard
Dermis
Porcine
Yes
Yes

FlexHD™
MTF
Dermis
Human
No
No

Periguard®
Synovis
Pericardium
Bovine
Yes
Yes

Permacol™
Covidien
Dermis
Porcine
Yes
Yes

Strattice®
LifeCell
Dermis
Porcine
No
Yes

Surgimend®
TEI
Dermis
Bovine fetal
No
Yes

Surgisis®
Cook
Intestinal submucosa
Porcine
No
Yes

Tutopatch®
Tutogen

Pericardium
Bovine
No
Yes

Veritas®
Synovis
Pericardium
Bovine
No
Yes

XenMatrix TM
CR Bard
Dermis
Porcine
No
Yes

BioA®
WL Gore
Synthetic bioabsorbable

N/A
Yes

TIGR®
Novus Scientific
Synthetic bioabsorbable


N/A
Yes





References
1. Melman L et al. Proceedings of World Hernia Congress. Berlin, Germany. 2009
2. Melman L et al. Histologic Evaluation of Crosslinked and Non-crosslinked Biologic Mesh Materials in a Porcine Model of Mature Ventral Incisional Hernia Repair. Proceedings of American Hernia Society: Hernia Repair 2010. Orlando, FL. 2010
3. Blatnik J, Jin J, Rosen M. Abdominal hernia repair with bridging acellular dermal matrix--an expensive hernia sac. Am J Surg. 2008 Jul;196(1):47-5
4. Bluebond-Langner R, Keifa ES, Mithani S, Bochicchio GV, Scalea T, Rodriguez ED. Recurrent abdominal laxity following interpositional human acellular dermal matrix. Ann Plast Surg. 2008 Jan;60(1):76-80.
5. Jin J, Rosen MJ, Blatnik J, McGee MF, Williams CP, Marks J, Ponsky J. Use of acellular dermal matrix for complicated ventral hernia repair: does technique affect outcomes? J Am Coll Surg. 2007 Nov;205(5):654-60.
6. Saettele TM, Bachman SL, Costello CR, Grant SA, Cleveland DS, Loy TS, Kolder DG, Ramshaw BJ. Use of porcine dermal collagen as a prosthetic mesh in a contaminated field for ventral hernia repair: a case report. Hernia. 2007 Jun;11(3):279-85.
7. Candage R, Jones K, Luchette FA, Sinacore JM, Vandevender D, Reed RL 2nd. Use of human acellular dermal matrix for hernia repair: friend or foe? Surgery. 2008 Oct;144(4):703-9.
8. Harold KL, et al. Early Results of a Prospective Randomized Study Using Acellular Human Dermal Matrix (Alloderm) to Prevent Parastomal Herniation. Proceedings of American Hernia Society: Hernia Repair 2010. Orlando, FL. 2010
9. Lo Menzo E, Martinez JM, Spector SA, Iglesias A, Degennaro V, Cappellani A. Use of biologic mesh for a complicated paracolostomy hernia. Am J Surg. 2008 Nov;196(5):715-9.
10. Oelschlager BK, Pellegrini CA, Hunter J, Soper N, Brunt M, Sheppard B, Jobe B, Polissar N, Mitsumori L, Nelson J, Swanstrom L. Biologic prosthesis reduces recurrence after laparoscopic
paraesophageal hernia repair: a multicenter, prospective, randomized trial. Ann Surg. 2006 Oct;244(4):481-90.
11. Stadlhuber RJ, Sherif AE, Mittal SK, Fitzgibbons RJ Jr, Michael Brunt L, Hunter JG, Demeester TR, Swanstrom LL, Daniel Smith C, Filipi CJ. Mesh complications after prosthetic reinforcement of hiatal closure: a 28-case series. Surg Endosc. 2009 Jun;23(6):1219-26.
12. Rosen MJ. Biologic mesh for abdominal wall reconstruction: a critical appraisal. Am Surg. 2010 Jan;76(1):1-6.
13. Harth KC, Rosen MJ. Major complications associated with xenograft biologic mesh implantation in abdominal wall reconstruction. Surg Innov. 2009 Dec;16(4):324-9.
14. Gina Adrales, M.D. Biological Meshes – Indications and Shortcomings. Challenging Hernias Post-Graduate Course. 12thWorld Congress of Endoscopic Surgery. April 15, 2010

"The last 30 years has seen major developments in the management of gallstone related disease, which in the United States alone costs over 6 billion dollars per annum to treat," write Earl Jon Williams, from the British Society of Gastroenterology (BSG) and the Royal Liverpool University Hospital, Liverpool, United Kingdom, and colleagues. "As a consequence clinicians are now faced with a number of potentially valid options for managing patients with suspected CBDS. It is with this in mind that the following guidelines have been written."
New imaging techniques allow accurate visualization of the biliary system without requiring duct instrumentation. These include magnetic resonance (MR) cholangiography and endoscopic ultrasound (EUS). Use of endoscopic retrograde cholangiopancreatography (ERCP) is now widespread and is considered a routine procedure. Laparoscopic cholecystectomy has largely replaced open cholecystectomy, and it is often accompanied by laparoscopic exploration of the common bile duct (LCBDE).
The BSG commissioned these guidelines, which were subsequently reviewed, revised, and endorsed by the Clinical Standards and Services Committee of the BSG, the BSG Endoscopy Committee, the ERCP stakeholder group, the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, and the Royal College of Radiologists.
After a preliminary search of the literature in 2004 of PubMed and MEDLINE, the findings were summarized and were presented to the BSG Endoscopy Committee, which developed principal clinical questions to be addressed by the guidelines. A multidisciplinary guideline-writing group then wrote provisional guidelines.
Some of the specific recommendations are as follows:
• Hepatobiliary cases should be discussed in a multidisciplinary setting (grade C).
• Symptomatic patients in whom evaluation suggests ductal stones should undergo extraction if possible (grade B).
• Transabdominal ultrasound scanning (USS) is recommended as a preliminary investigation for CBDS, but it is not a sensitive test for this condition (grade B).
• EUS and MR cholangiography are both highly effective at confirming CBDS; patient suitability, accessibility, and local expertise should help decide between the 2 procedures (grade B).
• When performing endoscopic stone extraction (ESE), the endoscopist should be assisted by a technician or radiologist who can help with fluoroscopy, a nurse for safety monitoring, and an additional endoscopy assistant or nurse to manage guide wires and other technical aspects as needed (grade C).
• ERCP should be done only in patients who are expected to require an intervention; it is not recommended for use solely as a diagnostic test (grade B).
• Full blood count and prothrombin time/international normalized ratio (PT/INR) should be performed within 72 hours before biliary sphincterotomy for ductal stones; patients with abnormal clotting should undergo subsequent management based on locally agreed guidelines (grade B).
• For patients treated with anticoagulants but who are at low risk for thromboembolism, anticoagulants should be discontinued before endoscopic stone extraction if biliary sphincterotomy is planned (grade B) as should newer antiplatelet agents (eg, clopidogrel), 7 to 10 days before biliary sphincterotomy (grade C). Use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and low-dose heparin should not be considered a contraindication to biliary sphincterotomy (grade B).
• Patients with biliary obstruction or previous features of biliary sepsis should receive prophylactic antibiotics (grade A).
• Sphincterotomy initiated with use of pure cut may be preferred in patients with risk factors for post-ERCP pancreatitis but not biliary sphincterotomy–induced hemorrhage (grade A).
• In most patients undergoing stone extraction, balloon dilation of the papilla should be avoided because the risk for severe post-ERCP pancreatitis is increased vs biliary sphincterotomy (grade A).
• Short-term use of a biliary stent, followed by further endoscopy or surgery, is recommended to ensure adequate biliary drainage in patients with CBDS that have not been extracted (grade B).
• Use of a biliary stent as sole treatment of CBDS should be limited to patients with limited life expectancy or prohibitive surgical risk, or both (grade A).
• Pre-cut is a risk factor for complication and should be used only by those with appropriate training and experience and only in patients for whom subsequent endoscopic treatment is essential (grade B).
• Operative risk should be evaluated before scheduling intervention, and endoscopic therapy should be considered as an alternative in high-risk patients (grade B).
• Intraoperative cholangiography or laparoscopic ultrasound can detect CBDS in patients who are suitable for surgical exploration or postoperative ERCP (grade B).
• In patients undergoing laparoscopic cholecystectomy, transcystic and transductal exploration of the common bile duct are both considered appropriate for removal of CBDS (grade A).
• When minimally invasive techniques fail to achieve duct clearance, open surgical exploration is still considered to be an important treatment option (grade B).
The guidelines also discuss supplementary treatments including mechanical lithotripsy, extracorporeal shock wave lithotripsy, electrohydraulic lithotripsy and laser lithotripsy, percutaneous treatment, and oral ursodeoxycholic acid. Management of specific clinical scenarios is also presented.
"Biliary sphincterotomy and endoscopic stone extraction (ESE) is recommended as the primary form of treatment for patients with CBDS post cholecystectomy," the authors of the guidelines write. "Cholecystectomy is recommended for all patients with CBDS and symptomatic gallbladder stones, unless there are specific reasons for considering surgery inappropriate. Patients with CBDS undergoing laparoscopic cholecystectomy may be managed by laparoscopic common bile duct exploration (LCBDE) at the time of surgery, or undergo peri-operative ERCP."

Clinical Context
In the last 3 decades, major developments in the management of gallstone-related disease have extended the range of suitable options for evaluation and treatment of CBDS. The high healthcare costs associated with this condition (> 6 billion dollars per year in the United States alone) warrant new guidelines providing recommendations for clinical management.
ERCP is now widely available and is performed routinely, and laparoscopy has mostly obviated the need for open cholecystectomy. New imaging techniques facilitating less invasive visualization of the biliary tree include MR cholangiography and EUS.

Study Highlights
• Multidisciplinary management is recommended for hepatobiliary cases.
• Transabdominal USS is not a sensitive test for CBDS, but it is suitable as a preliminary investigation.
• EUS and MR cholangiography are both highly effective at confirming CBDS. Patient-specific factors, local availability, and local expertise should guide the choice between the 2 procedures.
• Symptomatic patients with suspected ductal stones based on evaluation should undergo extraction if possible.
• Biliary sphincterotomy and ESE are recommended as the primary forms of treatment of patients with CBDS postcholecystectomy.
• Unless there are specific reasons for considering surgery inappropriate, cholecystectomy is recommended for all patients with CBDS and symptomatic gallbladder stones.
• Patients with CBDS undergoing laparoscopic cholecystectomy may be treated by LCBDE at the time of surgery or undergo perioperative ERCP.
• Endoscopists performing ESE should be assisted by a technician or radiologist who can help with fluoroscopy, a nurse for safety monitoring, and an additional endoscopy assistant or nurse to manage technical aspects as needed.
• ERCP should be done only in patients who are expected to require an intervention; it is not recommended solely for diagnostic use.
• Full blood count and PT/INR should be performed within 72 hours before biliary sphincterotomy for ductal stones; patients with abnormal clotting should be treated according to local protocol.
• For patients treated with anticoagulants but at low risk for thromboembolism, anticoagulants should be discontinued before ESE if biliary sphincterotomy is planned (grade B) as should newer antiplatelet agents. Use of aspirin, NSAIDs, and low-dose heparin should not be considered a contraindication to biliary sphincterotomy.
• Antibiotic prophylaxis should be given to patients with biliary obstruction or previous features of biliary sepsis.
• Sphincterotomy initiated with use of pure cut may be preferred in patients with risk factors for post-ERCP pancreatitis but not biliary sphincterotomy–induced hemorrhage.
• Balloon dilation of the papilla should be avoided in most patients undergoing stone extraction because the risk for severe post-ERCP pancreatitis is increased vs biliary sphincterotomy.
• For CBDS that have not been extracted, short-term use of a biliary stent, followed by further endoscopy or surgery, is recommended to ensure adequate biliary drainage.
• Only patients with limited life expectancy or prohibitive surgical risk, or both, should undergo use of a biliary stent as sole treatment of CBDS.
• Pre-cut increases the risk for complication and should be used only by those with appropriate training and experience and only for patients in whom subsequent endoscopic treatment is essential.
• Operative risk should be evaluated before surgery is scheduled. In high-risk patients, endoscopic therapy should be considered as an alternative.
• In patients deemed suitable for surgical exploration or postoperative ERCP, intraoperative cholangiography, or laparoscopic ultrasound can detect CBDS.
• Transcystic and transductal exploration of the common bile duct are both considered appropriate for removal of CBDS in patients undergoing laparoscopic cholecystectomy.
• Open surgical exploration is still considered to be an important treatment option when minimally invasive techniques do not achieve duct clearance.
• Supplementary treatments may include mechanical lithotripsy, extracorporeal shock wave lithotripsy, electrohydraulic lithotripsy and laser lithotripsy, percutaneous treatment, and oral ursodeoxycholic acid.


Pearls for Practice
• Transabdominal USS is recommended as a preliminary investigation for CBDS, but it is not a sensitive test for this condition. EUS and MR cholangiography are both highly effective at confirming CBDS; patient suitability, accessibility, and local expertise should help decide between the 2 procedures.
• Biliary sphincterotomy and ESE are the primary forms of treatment recommended for patients with CBDS postcholecystectomy. For all patients with CBDS and symptomatic gallbladder stones, cholecystectomy is recommended, unless there are specific reasons for considering surgery inappropriate. Patients with CBDS undergoing laparoscopic cholecystectomy may be treated by LCBDE at the time of surgery or undergo perioperative ERCP.


Based on the BSG guidelines, which of the following statements about evaluation of CBDS is correct?

Transabdominal USS is a sensitive test for CBDS

EUS is significantly less effective than MR cholangiography for confirming CBDS

EUS is significantly more effective than MR cholangiography for confirming CBDS

Transabdominal USS is recommended as a preliminary investigation for CBDS

Based on the BSG guidelines, which of the following statements about treatment of CBDS is not correct?

Perioperative ERCP is not recommended for patients with CBDS undergoing laparoscopic cholecystectomy

Biliary sphincterotomy and ESE are recommended as the primary forms of treatment of patients with CBDS postcholecystectomy

Cholecystectomy is recommended for all patients with CBDS and symptomatic gallbladder stones, unless they are not surgical candidates

Patients with CBDS undergoing laparoscopic cholecystectomy may be treated by LCBDE at the time of surgery

"If we could artificially produce tissue of the density and toughness of fascia and tendon, the secret of the radical cure of the hernia repair would be discovered."
Theodore Bilroth 1857
Although significant advances in herniorrhaphy have occurred since Bilroth's statement 150 years ago, hernia repair remains a challenge to the general surgeon. For many years, the field of hernia prosthetics was fairly static and options were limited. However, today when the operating room (OR) nurse asks you what mesh you would like for your patient, the choices can be overwhelming. With data to support or refute almost any material, and "reps" who are more than willing to offer their biased opinion, deciphering the data can be difficult. That being said, other than technique, choosing the correct mesh is one of the most critical factors in determining the risk of recurrence, infection, and chronic pain. While there is probably no universally superior material or manufacturer, understanding the characteristics of each type of prosthetic will enable the surgeon to maximize the results for their patients.
At this year's annual SAGES meeting in Philadelphia, a joint consensus panel with the American Hernia Society (AHS) was convened entitled: "The Explosion of Biomaterials for Hernia Repair; What Do I Do?" The panel was comprised of experts in the field of hernia repair including moderators Maurice Arregui, MD, and Guy Voeller, MD. It provided an excellent overview of the current state of mesh prosthetics for hernia repair. The following is a review of this consensus panel with additional comments from the author.
Synthetic Meshes: Types, Costs, Advantages, and Disadvantages
Bruce Ramshaw, MD, Chief of Surgery at The University of Missouri, began the session with a review of current options for synthetic hernia repair. He reviewed the modern history of mesh starting with Francis Usher's introduction of polypropylene (PP) in 1958.[1]
Mesh Types
Woven mesh. PP is a monofilament, hydrophobic, large pore mesh that has been one of the primary "work horses" in hernia surgery for the past 50 years. Currently PP comes in a variety of weaves including single strand, double strand, and multifilament. Ramshaw highlighted the recent development of lightweight (LW) PP, which utilizes a lighter PP strand with larger interstices or pores. He compared it to polyester, which was popularized in Europe in 1960 with the Rives-Stoppa technique.[2] PP and polyester are both woven, macroporous mesh; however, polyester is multifilamented and hydrophilic.
Nonwoven mesh. Expanded polytetrafluoroethylene (ePTFE), a derivative of Teflon®, is the second major class of synthetic mesh. Developed in the 1970s, ePTFE has a proven track record in herniorrhaphy. In contrast to the woven meshes, ePTFE has a microporous, smooth textured construct that minimizes tissue ingrowth. This is a critical factor in laparoscopic ventral hernia repair, where the mesh is placed in the peritoneal cavity in juxtaposition to the bowel and other viscera. Refinements in ePTFE have included a composite material that has a larger pore on the abdominal wall side to help promote ingrowth (Dual Mesh®) and antibiotic impregnation (Dual Mesh Plus®). In an effort to maximize mesh fixation, other manufacturers have coupled ePTFE with PP. (Composix®).
Costs and Advantages of Using Mesh Repair
After reviewing the common types of synthetic meshes, Dr. Ramshaw discussed cost and the advantages of using mesh for repair. In general the traditional synthetics are the least expensive, followed by the barrier meshes, with the biomeshes (discussed below) representing the most expensive group.
Although mesh repair has higher material costs compared to primary closure, bridging the hernia defect with a prosthetic enables a tension-free repair, which should reduce recurrence, lessen pain, speed recovery, and ultimately yield lower overall costs. This has been demonstrated in multiple clinical studies, including that of Burger and colleagues[3] who examined the recurrence rate in ventral hernia repairs. In this study, patients without mesh repair had a 62% recurrence compared to 32% with mesh.
Disadvantages of Mesh Repair
Despite the numerous advantages of mesh repair, implantation of a permanent prosthetic can have deleterious effects. Dr. Ramshaw presented numerous video clips demonstrating mesh-related fistulas and bowel adhesions, as well as prosthetics that had undergone extreme contraction, migration, and malformed rigid configurations. He reviewed some of his institution's data suggesting that host-related responses may oxidize the PP mesh, making it more brittle and less compliant. A similar end result may occur due to hydrolysis of the mesh. According to Dr. Ramshaw, ePTFE does not seem to be as susceptible to hydrolysis or oxidation; however, it is not immune to contraction.
In conclusion, Dr. Ramshaw emphasized the need for further development of biomeshes. He reminded the audience that some of the traditional synthetic hernia meshes were initially designed and tested for the textile industry and what may be a good material for household furniture may not necessarily be ideal for human abdominal wall reconstruction! He ended with a reference to a new class of "nano" meshes that combine a strong bio-scaffold with growth factors and inflammatory inhibitors. Perhaps 1 day Bilroth's dream will come true.
Barrier-Coated Meshes
The development and refinement of laparoscopic ventral hernia repair (LVHR) has been a major innovation in the field of herniorraphy. The benefits of LVHR include lower recurrence rates and wound complications, improved diagnosis of occult hernias, less morbidity, and fewer mesh-related infections. Many believe that LVHR now represents the gold standard for ventral hernia repair (VHR).
Surgeons performing open VHR with mesh have several options for mesh positioning:
• Intraperitoneal onlay mesh technique (IPOM);
• Preperitoneal or retro-rectus placement (Rives-Stoppa); and
• Primary closure with mesh onlay.
However, LVHR requires placement of mesh within the peritoneal cavity. Thus, it is imperative that any material used during LVHR has minimal impact on the adjacent intra-abdominal anatomy.
Traditionally, ePTFE has been the material of choice for IPOM or LVHR. Brent Matthews, MD, Associate Professor of Surgery at Washington University reviewed the emerging field of absorbable barrier-coated meshes that provide another material option for intraperitoneal mesh placement. Dr. Matthews began his presentation by highlighting the problems of placing unprotected macroporous mesh in the peritoneum. He sited a study by Halm and colleagues[4] that examined the impact of mesh position on the outcomes of 66 patients who had VHR and required a subsequent laparotomy.Compared to patients with preperitoneal mesh repairs, patients with intraperitoneal mesh had higher perioperative complications (76% vs 29%), more intra-abdominal adhesions (62% vs 26%) and fistulas (5% vs 0%), and required more bowel resections (20% vs 0%). It should be noted that 93% of these patients had unprotected PP placed at their initial VHR.
Dr. Matthews then reviewed the 4 currently available absorbable barrier-coated meshes (ABCMs) in the United States. These ABCMs all use either a PP or polyester mesh foundation that is coated with a temporary "barrier" designed to minimize tissue ingrowth into adjacent bowel or viscera. He added later, however, that ePTFE, whose microporous surface provides a permanent adhesive barrier, is, in his words, "the gold standard" to which other ABCMs must be compared.
The ABCMs exploit a natural process called neo-peritonealization. When a mesh is implanted in the peritoneal cavity, the host forms a new (neo) peritoneum over the material. This process, which can take several weeks, ultimately has the effect of placing the mesh in a more protected preperitoneal position, assuming the mesh barrier remains intact during this process. The specific properties of each ABCM are detailed in Table 1.
Table 1. Properties of Absorbable Barrier-Coated Meshes
Mesh Manufacturer Permanent Barrier Longevity (days) Weight (g/m2)*
ParietexTM Composite Covidien Polyester (RW) Atelocollagen Type 1, polyethylene glycol, glycerol 20 75
C-QurTM Atrium PP (LW) Omega-3 fatty acid 90-180 50
PROCEEDTM Ethicon PP (LW) Oxygenated regenerated cellulose + polydioxanone (PDS) within 30 days 45
SeprameshTM Davol PP (LW) Seprafilm within 30 days 102
*Weight is after absorption of barrier
Dr. Matthews explained that SeprafilmTM, PROCEEDTM, and Parietex CompositeTM all have barrier coatings that are completely absorbed within 30 days (according to the patent application data), while C-Qur'sTM omega-3 barrier coating lasts about 90 to 120 days
While it is unclear how each of these different barrier coatings translates to clinical outcomes in humans, there is evidence that ABCMs produce fewer intra-abdominal adhesions compared to uncoated macroporous (PP of polyester) mesh.
Dr. Matthews cited a study by Arnaud and colleagues,[5] demonstrating that the ParietexTM composite had fewer visceral adhesions when compared to unprotected polyester (18% vs 77%). In a similar study by Balique and colleagues,[6] ParietexTM demonstrated an ultrasonic adhesion-free abdomen in 86% of patients at 1 year. Both studies utilized a validated ultrasound technique to grade the extent of intra-abdominal adhesions. However, this technique (ultrasound) was not able to assess adhesion tenacity, which may be a more clinically important factor. Furthermore, none of the adhesion scores were confirmed with laparoscopy. Currently, a study is ongoing at Dr. Matthews' institution evaluating adhesion area, tenacity, and adhesiolysis time. According to Dr. Matthews, preliminary data has shown higher adhesions and tenacity with unprotected macroporous meshes.
Quality of Life With Different Meshes
Recurrence Rates
One of the primary goals in hernia surgery is to provide a secure repair with a low long-term recurrence rate. Surgical techniques that incorporate a mesh repair have undoubtedly helped to lower the recurrence rate of both inguinal and ventral hernias. The current generation of mesh products is far from perfect and recurrence rates after mesh repair can be relatively high. In fact, Dr. Ramshaw, in his review of synthetic hernia repair, raised the provocative question: does mesh only serve to delay the recurrence of hernias? He cited Flum and colleagues,[7] who concluded that long-term reoperative rates for ventral hernia, which presumably reflects recurrence, did not differ with mesh vs primary (no mesh) repair. However, this was a large population-based study that did not randomize patients or control for exact repair technique.
Alternatively, Scott Roth, MD, a surgeon at The University of Maryland argued that there are overwhelming data that mesh repairs significantly reduce hernia recurrence. He sited a landmark study[8] of incisional hernias in The New England Journal of Medicine that demonstrated a 48% recurrence rate at 3 years with a primary, suture repair compared to 20% recurrence rate with mesh.
Mesh-Related Complications
With the increased utilization of hernia prosthetics, the incidence of mesh-related complications has also risen. Although rare, mesh infections and enterocutaneous fistulas are a devastating complication that can have significant effects on long-term quality of life. Furthermore, a growing body of literature suggests that mesh can increase chronic pain and discomfort in the form of a foreign body sensation, excessive rigidity, and collateral nerve and tissue inflammation. Multiple high volume (> 1000 cases) studies have demonstrated a relatively high incidence of chronic pain after inguinal hernia repair. In an effort to improve post-herniorrhaphy quality of life, prosthetic manufacturers are increasingly focused on developing meshes that have a more favorable graft-host profile.
Dr. Roth discussed the influence of mesh on quality of life and chronic pain after hernia repair. He began by reviewing the growing trend of prosthetic hernia repairs. According to Dr. Roth, the adoption of the Lichtenstein technique, as well as laparoscopic approaches to inguinal hernias, has led to a significant increase in mesh repairs for these hernias. For example, in 2003 there were over 750,000 inguinal hernia repairs in the United States with over 90% of these procedures utilizing mesh. Similarly, in 2004 it is estimated that there were 300,000 incisional hernia repairs with more than 50% employing mesh.
Mesh Weights and Their Impact on Outcomes
Dr. Roth provided a brief history of the evolution of mesh beginning with the first description of silver coils in 1894 to the development of the current generation of meshes including PP, polyester, and ePTFE. The primary focus of his review was the differences in outcomes between the traditional heavyweight (HW) meshes and the newer lightweight (LW) materials.
LW meshes offer several theoretical advantages over HW materials. Because LW meshes have less foreign material (measured in g/m2), compared with HW meshes they produce a less rigid repair that more closely approximates native tissue compliance, with the end result being a more comfortable repair for the patient. Furthermore, reducing the concentration of material may lessen the inflammatory and foreign body response, which is thought to be a factor in pain and mesh contraction. Although the tensile strength of LW mesh is lower than that of HW mesh, it still exceeds bursting strength of native tissue.
While there have been reports of higher recurrence rates with LW mesh, it is thought that most recurrences are related to mesh migration and not mesh rupture. It has been postulated that the less aggressive ingrowth of LW mesh combined with composites that utilize absorbable weaves makes these materials more prone to migration. Dr. Roth reviewed 5 recent studies that examined the potential benefits of LW mesh.
In 2005 O'Dwyer and colleagues[9] examined the incidence of chronic pain after open inguinal hernia repair. This was a prospective study of 321 patients undergoing primary Lichtenstein repair. Patients were randomized to either LW mesh (32 g/m2) repair or HW PP (85 g/m2). At 1 and 3 months after surgery there was no difference in the incidence of pain or "return to activities." However, 1 year after surgery, patients with LW mesh had a statistically significant higher number of recurrences compared to HW patients (5.6% vs 0.4%; P = .037). Dr. Roth did not discuss the significantly higher incidence of "pain of any severity" in the HW group at 1 year postop (51.6% vs 39.5%, P = .033).
Akolekar and colleagues[10] examined the effect of LW vs. HW mesh on recurrence after laparoscopic total extraperitonal (TEP) inguinal herniorrhaphy. In their study, 371 hernias were repaired with LW mesh while 861 defects were repaired with HW mesh.[10] Overall, there was no significant difference in recurrence rates (4.3% for LW vs 2.8% for HW). However, the authors were concerned about the trend of higher recurrence rates for the LW group given the shorter follow-up time in this group (14 months vs 22 months for HW patients). As in the US laparoscopic VA trial,[11] this study's results were confounded by a high number of operating surgeons being trainees. In the O'Dwyer study,[9] 30% of the LW repairs were performed by residents vs 14% in the HW group. This included a "high activity" surgeon who only used HW mesh and had "no teaching responsibility." In a 2006 publication by Horstmann and colleagues,[11] PP weight was found to be proportional to the risk of postoperative complications in inguinal hernia patients. This study involved 632 patients undergoing laparoscopic transabdominal preperitoneal (TAPP) repairs with 3 varying weights of PP: (1) HW mesh, (2) LW mesh, and (3) extra-lightweight mesh (16 g/m2).Patients who received the HW mesh had a significantly higher incidence of postoperative complications including seroma and hematoma. At 12-month follow-up, the HW group also had a significantly higher incidence of foreign body sensation and "undue sensitivity to weather changes." Patients who had either moderate or severe impairment of quality of life (QOL) prior to surgery experienced a uniform improvement in QOL after hernia repair, regardless of the type of mesh. However it was concerning that patients who were asymptomatic or who had minimal QOL impairment preoperatively experienced a decrease in QOL in the HW and LW group; with only the extra-lightweight patients experiencing an improvement in QOL.
Post and colleagues[12] also examined the relationship between mesh weight and QOL in patients undergoing Lichtenstein repair.LW repairs yielded a significantly lower incidence of pain (with activity) and foreign body mesh sensations at 6 months postoperatively. As with most other studies, there was an improvement in overall QOL after repair that was independent of mesh weight. This study was limited in size (122 hernia repairs) and follow-up (6 months).
One of the higher volume single surgeon studies was published by Paajanem in 2007.[13] In his study of Lichtenstein repairs, Paajanem randomized 228 patients to either HW or LW mesh. At 1 year there was no difference in the incidence of pain, foreign body sensation, or recurrence rates between HW and LW groups. He did demonstrate that between the first and second year after surgery, patients have improvement in all of the above parameters. His results suggest that the nadir of adverse symptoms following inguinal repair may be at least 2 years after surgery. This is important because many of the studies examining mesh QOL have limited follow-up up (6 to 12 months).
Dr. Roth concluded with a brief discussion of ventral hernia repairs. He reviewed the commonly used permanent and absorbable barrier coated meshes and stated that they "all are associated with adhesions to a variable extent." According to Dr. Roth, the relevance of mesh-related adhesions to obstructions, fistulae, and quality of life are "absolutely unknown." Similarly, he stated that while it is assumed that HW meshes experience more contraction, it is unclear whether this translates to a higher risk of pain and recurrence.
In summary, Dr. Roth stated that there may be a trend toward less pain and foreign body sensation with LW mesh and this benefit may come at the expense of a higher recurrence rate. In addition, regardless of mesh weight, most patients seem to enjoy an improvement in QOL after hernia repair.
Yuri Novitsky, MD, Director of the Hernia Center at The University of Connecticut Health Center, Farmington, Connecticut, reviewed the clinical effect of aberrant inflammatory responses to mesh prosthetics, especially foreign body reactions that may increase mesh morbidity.
Picking up where Dr. Roth left off, he examined the histologic advantages of LW mesh while conceding that there is no clear definition of "lightweight mesh." For the purpose of his discussion, Dr. Novitsky defined HW mesh as > 95 g/m2 and reduced or LW mesh as < 70 g/m2.
Dr. Novitsky reviewed data from 3 animal studies[14-16] that confirmed the benefits of LW mesh. Klinge and colleagues[15] described the normal tissue healing process which involves an initial period of increased fibroblastic, macrophage and granulocyte activity that peaks after 7-14. After 90 days there is uniform collagen deposition and almost complete disappearance of inflammatory cells. In contrast, in the presence of a foreign body (ie, mesh) there is an exaggerated inflammatory response with maintenance of inflammatory cells even at 90 days and excessive fibrosis with formation of a "scar plate" around the mesh. Although LW mesh induces an abnormal inflammatory response, when compared to HW mesh it is more blunted, with less scar plate formation and foreign body reaction. This may translate to what is seen clinically (less contraction and more compliance). Compared to HW mesh, LW mesh also yielded lower levels of apoptosis and Ki-67 which are 2 markers of cell turnover and inflammation.
In a recent publication by Dr. Novitsky,[16] various prosthetics were implanted in rabbits and evaluated 1 year later.ePTFE and lightweight PP had significantly lower levels of apoptosis and Ki-67 compared to HW PP and the ePTFE/PP composite. Persistently elevated levels of apoptosis have also been observed in humans up to 5 years post implantation.[17-19]
Dr. Novitsky also reviewed some of the clinical data examining differences between LW and HW synthetic meshes. In addition to critiquing the Post and O'Dwyer studies (see above), he cited a 2006 study by Bringman and colleagues[20] where590 patients were randomized to Lichtenstein repair with either HW (80 g/m2) or LW (30 g/m2)mesh. The average follow-up interval was 3 years, with a minimum of 30 months. There was no significant difference in recurrence (3.7% vs 3.6%), testicular atrophy, pain with activity, or long-term postoperative narcotic use. In fact, on their 20-point questionnaire, there were only 3 areas of significant difference; groin tenderness on palpation (HW: 3.3% vs LW: 0.8%, P = .49); pain with positional change (HW: 13.6% vs LW: 7.6, P = .29) and mesh sensation (HW: 22.6% vs LW: 14.7%, P = .025). However, there was no difference in the number of patients reporting a "normal sensation" or "discomfort" in the groin.
The Ideal Synthetic Mesh -- Has it Arrived?
Dr. Novitsky began with an emphatic "no" when answering the question above. According to Dr. Novitsky, the ideal synthetic mesh would have all of the following properties:
• Durable tensile strength;
• No physical alteration by host tissue (contraction);
• Hypoallergenic;
• Noncarcinogenic;
• Resistance to infection;
• Effective tissue ingrowth without excessive inflammation or foreign body reaction; and
• Cost effectiveness.
Other important factors include: compliance, ease of handling, and reduced risk of fistula and seroma formation.
In summary Dr. Novitsky emphasized the equivocal clinical data pertaining to synthetic meshes. He stated that there is "insufficient evidence" to establish superiority of PP vs polyester; monofilament vs multifilament; and pore size (controlling for weight). While arguing that there is a "vast" body of evidence supporting the immunohistochemical benefits of LW mesh, he conceded that there are no clear data demonstrating clinical benefits of LW mesh other than mild-to-moderate reductions in groin pain.
Biologic Meshes -- Sources, Advantages, and Cost
One of most recent trends in hernia prosthetics has been the development of the biologic meshes, aka "biomeshes." Human and porcine acellular dermal matrices, which where introduced in the mid 1990s,[21] were initially used for coverage of burn wounds. Recently the biomeshes have established a higher profile in hernia and abdominal wall reconstruction, especially in the arena of infected wounds and "damage control" surgery.
Dr. Scott Helton, Chairman of Surgery at The Hospital of St. Raphael in New Haven, concluded the session with a review of the status of biomeshes in hernia repair. He began by highlighting the dramatic growth in the field. According to Dr. Helton, in the last 2 years, the number of available biomeshes in the United States has grown from 3 to 13. However, he pointed out that 6 of these products have no peer-reviewed published animal or human data.
There are 3 biomesh categories: human acellular dermis, xenogenic acellular dermis (porcine and bovine), and acellular porcine small intestinal submucosa (Table 2). All of these constructs use a matrix of proteins, including collagen, elastin, glycoproteins, and growth factors, which provide a scaffold for ingrowth of host cells and deposition of mature collagen, with ultimate resorption of the biomesh. Dr. Helton also briefly mentioned bovine pericardium, which is primarily used for staple line reinforcement.
He then discussed the key components that vary between each biomesh product:
• The process for extracting donor cells and contaminant (ie, viral) material;
• Removing potentially deleterious xenogenic proteins that may promote abnormal host inflammation; and
• Hydration and freeze-drying, which alter the operating room "prep time" of the product.
In addition, there are also numerous host factors, such as anatomical position of the biomesh, the degree and type of local wound infection, and local inflammatory mediators that affect mesh strength, longevity, and the ability to resist infection. In Dr. Helton's words, it is often a race between mesh "incorporation, integration, and remodeling" and infectious forces attempting to degrade the biomesh.
Table 2. Biomeshes
Biomesh Type Products, Manufacturers
Human acellular dermis AlloDerm®, LifeCell

Flex HDTM, J&J

AlloMaxTM, Davol
Xenogenic acellular dermis PermacolTM (porcine), Tissue Science Laboratories

SurgiMendTM (bovine,calf), TEI Biosciences

CollaMendTM, (porcine) Davol

XenMatriX® (porcine), Brennen Medical LLC; Brennenmed.com

StratticeTM, LifeCell
Porcine small intestine submucosa Surgisis®, Cook Medical

FortaGen®, Organogenesis

Dr. Helton summarized the unique and advantageous properties of the biomeshes. He explained that the biomeshes are especially well suited for coverage and protection of exposed viscera (ie, the open abdomen). When compared to the polyglactin 910 absorbable woven mesh (VicrylTM), Dr. Helton stated that there is accumulating data that the biomeshes reduce the risk of fistula formation and accelerate vascularization and wound contracture. He also addressed the high cost of the biomeshes, but justified their use if it avoids an enterocutaneous fistula, which can cost "hundreds of thousands" of dollars. The biomeshes also appear to be more resistant to infection, which makes them an ideal choice for repair of infected hernias or repairs that are done during contaminated procedures, such as colectomy, ostomy closure/reinforcement, hysterectomy, or gastric bypass. Finally, there are data to support the use of biomeshes in hiatal repair and the concept of having an absorbable material in juxtaposition to the esophagus is appealing. However, the efficacy and safety of biomeshes in elective, clean, ventral or inguinal herniorrhaphy is unknown. There are concerns about long-term tensile strength and recurrence with the biomeshes.[22,23] For this reason, as well as cost, most surgeons continue to use a permanent synthetic material for clean ventral and inguinal herniorrhaphy.
Because the biomeshes are derived from transplanted animal tissue there have been concerns related to transmission of infectious agents. Although no case of an infection has been reported with a xenogenic biomesh, there is the theoretical possibility of viral or prion (notably, bovine spongioform encephalopathy) transmission. The risk of infection with human allogenic biomeshes is slightly higher with the primary concern being HIV and viral hepatitis. According to 2005 Centers for Disease Control (CDC) data, the risk of "disease transmission" with cadaveric grafts is 4 per million with most of these cases involving solid organ transplantation. Despite several well-publicized cases of improper organ procurement, the processing of biomeshes is extremely stringent and there have no reports of transmission with xenogenic or allogenic hernia biomeshes. There are also medical/legal issues related to utilizing animal grafts for hernia repair in patients who have religious or personal objections to implantation of animal tissue. Dr. Helton stressed the importance of informed consent before using any animal derived biomesh. Specifically, Islamic and Jewish faiths may prohibit porcine-derived biomesh, and these patients should be encouraged to consult with their religious leaders prior to surgery. Furthermore, the Jehovah's Witness' faith forbids receipt of any animal or human tissue or fluid.
Summary
Hernias will continue to be a common and vexing challenge to the general surgeon. While minimally invasive techniques and modern prosthetics have bolstered the surgeon's armamentarium, we have yet to realize the ultimate goal of recurrence free repairs that are free from any morbidity. Furthermore, despite a wealth of published data, many of the fundamental questions in herniorraphy remain unanswered. However, if the past is any predictor, the scientific and medical community will continue their march forward in search of Bilroth's "secret of the radical hernia repair."
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References
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References
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