Welcome to the links to information regarding synthetic medical mesh.
To assist those researching medical mesh complications , key words or phrases are in alphabetical order with their source links provided . The information is meant to be educational, pertinent and thought provoking material to those curious minds wondering why thousands of patients feel betrayed or abandoned by mesh manufacturers and the medical community. Over 100,000 women have retained legal help to claim for medical expenses , and for compensation for loss of quality of life. You would expect that there would be at least 50,000 adverse event reports filed to the FDA by their doctors. There is an alarming lack of reporting anywhere. One must ask why there are very few adverse events reported. Why is there so much silence ?
The FDA does not believe that the problems associated with
mesh procedures can be attributed exclusively to surgical skill/training. Restricting use of mesh to surgeons with a specified level of experience and training would not eliminate mesh-related complications. The FDA believes that vaginal placement of surgical mesh or POP repair inherently introduces risks of complications that are unique to the mesh itself.
(my questions/comments, inserted with the research content are in red print)
Most links provided require further reading after reading the sample excerpt......
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A.S.I.A:
http://freepdfhosting.com/962132b4b7.pdf
‘ASIA’ e Autoimmune/inflammatory syndrome induced by adjuvants
Yehuda Shoenfelda,b,*, Nancy Agmon-Levina
a The Zabludowicz Center for Autoimmune Diseases, Department of Medicine B’ Sheba Medical Center, Tel-Hashomer, Israel b Incumbent of the Laura Schwarz-kipp Chair for Research of Autoimmune Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Israel
...role of adjuvants in the pathogenesis of immune mediated diseases........
following exposure to a certain environmental factor [5e8].
Noteworthy, infections, toxins, and drugs were linked not only with
the occurrence of immune mediated conditions but also with their
clinical manifestations [7,8
adjuvant effect of biomaterials: (autoimmune initiation and exacerbation)
http://www.facebook.com/l.php?u=http%3A%2F%2Fgroups.bme.gatech.edu%2Fgroups%2Fbabensee%2Fproject1_innate.html&h=nAQF0_ecr
the biomaterial adjuvant effect depends on the form of the biomaterial carrier vehicle (implanted polymer scaffolds vs. minimally invasive injected polymer microparticles) (Bennewitz, Biomaterials, 2005).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988402/
IIntroduction: For functional tissue engineered devices, critical issues are maintenance of the cell phenotype, complex organ development with multiple cell types and 3-dimensionality, biomaterial scaffold design addressing mechanical, bio/chemical, and remodeling properties, and integration into living systems including host acceptance. While much consideration has been given issues such as cell source, induction and maintenance of cell differentiation, and development of novel scaffold materials, certain issues have received less attention, particularly how scaffold material selection can potentiate immune responses. Hence, scaffold material selection is a focus herein to improve host acceptance of tissue engineered devices.......
Upon implantation, tissue engineered devices elicit an innate immune response towards the biomaterial scaffold, known as the foreign-body response[1-3]; these devices also may elicit an adaptive immune response towards incorporated allo- or xenogeneic cells or their shed antigens[4]. Adaptive immune responses are potentiated by adjuvants in the antigen delivery system. These principles of engaging innate and adaptive immune responses towards foreign antigens are utilized in the pharmaceutical formulations for vaccine delivery using polymers, such as chitosan[5-9] and PLGA[5, 6, 10-13]; whereas, it would be detrimental to tissue engineered device function to engage adaptive immune response to shed foreign antigens and induction of tolerance would be preferred.
......These studies have demonstrated the potential for biomaterial scaffolds to act as adjuvants in enhancing the adaptive immune response to co-delivered antigen, presumably due to a material effect on DC maturation. Furthermore, tissue damage associated with the implantation of a construct may prime the site for the biomaterial adjuvant effect due to the generation of endogenous ‘danger signals’.
http://www.jidc.org/index.php/journal/article/view/21997935
Keywords: viral infection; bacterial infection; autoreactive lymphocyte; molecular mimicry; bystander activation; epitope spreading; autoimmune disease studies suggest that pathogens can trigger autoimmunity through molecular mimicry and their adjuvant effects during initiation of disease, and can promote autoimmune responses through bystander activation or epitope spreading via inflammation and/or superantigens.
http://www.ncbi.nlm.nih.gov/pubmed/22235043
“patient illustrates an example of ASIA (Autoimmune Syndrome Induced by Adjuvants), as her disease appeared following exposure to an adjuvant stimulus, with 'typical', although not well-defined, autoimmune manifestations.”
http://www.termedia.pl/Czasopismo/Reumatologia-18/Streszczenie-21947
keywords:adjuvants, immune response, autoimmune diseasesObservations of recent years have shown that similar clinical conditions may be associated with immune response hyperreactivity and proinflammatory action of adjuvants used.
http://www.hindawi.com/journals/bmri/2013/732182/
Biomaterials-Based Modulation of the Immune SystemAustin B. Gardner, Simon K. C. Lee, Elliot C. Woods, and Abhinav P. Acharya
Department of Bioengineering, University of California, Berkeley, CA 94720, USA Received 30 April 2013; Accepted 19 August 2013
Academic Editor: Soo-Hong Lee, Copyright © 2013 Austin B. Gardner et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract:The immune system is traditionally considered from the perspective of defending against bacterial or viral infections. However, foreign materials like implants can also illicit immune responses. These immune responses are mediated by a large number of molecular signals, including cytokines, antibodies and reactive radical species, and cell types, including macrophages, neutrophils, natural killer cells, T-cells, B-cells, and dendritic cells. Most often, these molecular signals lead to the generation of fibrous encapsulation of the biomaterials, thereby shielding the body from these biomaterials. In this review we will focus on two different types of biomaterials: those that actively modulate the immune response, as seen in antigen delivery vehicles for vaccines, and those that illicit relatively small immune response, which are important for implantable materials. The first serves to actively influence the immune response by co-opting certain immune pathways, while the second tries to mimic the properties of the host in an attempt to remain undetected by the immune system. As these are two very different end points, each type of biomaterial has been studied and developed separately and in recent years, many advances have been made in each respective area, which will be highlighted in this review.
age related concerns:
http://www.ajog.org/article/S0002-9378%2811%2901018-0/pdfSummary
One-year objective and functional outcomes of a randomized clinical trial of vaginal mesh for prolapsePresented orally at the 31st annual meeting of the American Urogynecologic Society, Long Beach, CA, Sept. 30-Oct. 2, 2010.
Andrew I. Sokol, MD, Cheryl B. Iglesia, MD, Bela I. Kudish, MD, Robert E. Gutman, MD, David Shveiky, MD, Richard Bercik, MD, Eric R. Sokol, MDReceived: April 21, 2011; Received in revised form: July 6, 2011; Accepted: August 4, 2011; Published Online: August 12, 2011
http://www.ajog.org/article/S0002-9378%2811%2901018-0/pdfSummary
One-year objective and functional outcomes of a randomized clinical trial of vaginal mesh for prolapsePresented orally at the 31st annual meeting of the American Urogynecologic Society, Long Beach, CA, Sept. 30-Oct. 2, 2010.
Andrew I. Sokol, MD, Cheryl B. Iglesia, MD, Bela I. Kudish, MD, Robert E. Gutman, MD, David Shveiky, MD, Richard Bercik, MD, Eric R. Sokol, MDReceived: April 21, 2011; Received in revised form: July 6, 2011; Accepted: August 4, 2011; Published Online: August 12, 2011
http://weill.cornell.edu/news/news/2015/06/pelvic-organic-prolapse-procedures-with-mesh-increase-leading-to-age-based-complications.html
Despite FDA warnings that a synthetic mesh used to treat a weakening of the female pelvis's walls can cause infection, pain, and disease recurrence, surgeons are increasing their use of the device. What's more, when compared to not using mesh, younger patients who undergo surgery with mesh for pelvic organ prolapse (POP) are more likely to have a repeat surgery the following year, and older patients are more likely to have complications while they're in the hospital, according to new research from Weill Cornell Medical College.
allergic reaction to synthetic materials:
http://academicdepartments.musc.edu/surgery/education/resident_info/supplement/suture_manuals/ethicon_wound_closure_manual.pdf
Some patients have allergies to specific suturing materials, metal alloys, or latex. ......These, on the other hand, will cause a heightened immune response in the form of an allergic reaction. This may interfere with the healing process. Therefore the surgeon should always check beforehand on a patients' allergies.
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autoimmune disease post mesh implantation :
http://www.jleukbio.org/content/87/3/385.full
Infections and autoimmunity: the multifaceted relationship
- Paolo Sfriso * , Anna Ghirardello * , Costantino Botsios * , Michele Tonon* , Margherita Zen * , Nicola Bassi * , Franco Bassetto † and Andrea Doria* , 1 Division of Rheumatology, Clinical and Experimental Medicine, and†Section of Plastic Surgery, Department of Medical and Surgical Sciences, University of Padova, Padova, Italy
- Correspondence: Division of Rheumatology, Department of Clinical and Experimental Medicine, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy. E-mail: [email protected]
http://informahealthcare.com/doi/abs/10.1080/08916930701574331
Enhanced recognition of reactive oxygen species damaged human serum albumin by circulating systemic lupus erythematosus autoantibodies 2007, Vol. 40, No. 7 , Pages 512-520 (doi:10.1080/08916930701574331
Zafar Rasheed, , Rizwan Ahmad, Naila Rasheed and Rashid AliDepartment of Biochemistry, Faculty of Medicine, AMU, Aligarh, 202002, IndiaDepartment of Biochemistry, SBSPGI, Balawala, Dehradun, 248161, India Division of Pharmacology, Central Drug Research Institute, P.B. No. 173, Lucknow, India Department of Biochemistry, Faculty of Medicine, JN Medical College, AMU, Aligarh, 202002, India, 91 9219345899, 91 135 2686231 [email protected]
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with autoantibodies as a near universal feature of the disease. Earlier investigations from our laboratory revealed increased oxidative damage in SLE patients. Therefore, we hypothesized that oxidative by-products, such as hydroxyl radical (√OH), could lead to neoantigens like √OH damaged human serum albumin (HSA), which could in turn initiate autoimmunity in SLE. In the present study, the binding characteristics of SLE autoantibodies with native and √OH damaged HSA were assessed. SLE patients (n = 74) were examined by direct binding ELISA and the results were compared with healthy age- and sex-matched controls (n = 44). High degree of specific binding by 52.7% of patients sera towards √OH damaged HSA, in comparison to its native analogue (p < 0.05) was observed. Normal human sera showed negligible binding with either antigen. Competitive ELISA and gel retardation assays reiterate the direct binding results. The increase in total serum protein carbonyl levels in the SLE patients was largely due to an increase in oxidized albumin. HSA of SLE patients (SLE-HSA) and normal subjects (normal-HSA) were purified. Spectroscopic analysis confirmed that the SLE-HSA samples contained higher levels of carbonyls than normal-HSA (p < 0.01). SLE-HSA was conformationally altered, with more exposure of its hydrophobic regions. Collectively, the oxidation of plasma proteins, especially HSA, might enhance oxidative stress in SLE patients.
Keywords: Systemic lupus erythematosus, autoimmunity, reactive oxygen species, human serum albumin
(the body uses an oxidative process to try break down foreign bodies..It produces hydrogen peroxide which not only damages surrounding tissus but it degrades the polypropylene mesh implants, the degradation products are Alcyl radical ( R ) (carbon centered free radical) , Peroxy radical (R-OO ) (oxygen centered radical ) Alkoxy radical (R-O ), Hydroperoxide (R-OOH Æ R-O + OH)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2665673/
ABSTRACT: Autoimmunity occurs when the immune system recognizes and attacks host tissue. In addition to genetic factors, environmental triggers (in particular viruses, bacteria and other infectious pathogens) are thought to play a major role in the development of autoimmune diseases. In this review, we (i) describe the ways in which an infectious agent can initiate or exacerbate autoimmunity; (ii) discuss the evidence linking certain infectious agents to autoimmune diseases in humans; and (iii) describe the animal models used to study the link between infection and autoimmunity.
Keywords: autoimmune disease, molecular mimicry, virus infection.....
There are multiple mechanisms by which host infection by a pathogen can lead to autoimmunity (Fig. 1). The pathogen may carry elements that are similar enough in amino acid sequence or structure to self-antigen that the pathogen acts as a self-‘mimic’. Termed ‘molecular mimicry’, T or B cells that are activated in response to the pathogen are also cross-reactive to self and lead to direct damage and further activation of other arms of the immune system. The pathogen may also lead to disease via epitope spreading. In this model the immune response to a persisting pathogen, or direct lysis by the persisting pathogen, causes damage to self-tissue. Antigens released from damaged tissue are taken up by APCs, and this initiates a self-specific immune response. ‘Bystander activation’ describes an indirect or non-specific activation of autoimmune cells caused by the inflammatory environment present during infection. A domino effect can occur, where the non-specific activation of one arm of the immune system leads to the activation of other arms. Lastly, infection may lead autoimmunity through the processing and presentation of ‘cryptic antigens’. In contrast to dominant antigenic determinants, subdominant cryptic antigens are normally invisible to the immune system. The inflammatory environment that arises after infection can induce increased protease production and differential processing of released self-epitopes by APCs.........Defining the genetic markers that predispose patients to different autoimmune diseases with a suspected infectious trigger would be an important contribution to defining the underlying disease pathogenesis.
http://www.nlm.nih.gov/medlineplus/ency/article/000816.htm
......In patients with an autoimmune disorder, the immune system can't tell the difference between healthy body tissue and antigens. The result is an immune response that destroys normal body tissues. This response is a hypersensitivity reaction similar to the response in allergic conditions.
In allergies, the immune system reacts to an outside substance that it normally would ignore. With autoimmune disorders, the immune system reacts to normal body tissues that it would normally ignore.
What causes the immune system to no longer tell the difference between healthy body tissues and antigens is unknown. One theory is that some microorganisms (such as bacteria or viruses) or drugs may trigger some of these changes, especially in people who have genes that make them more likely to get autoimmune disorders...... Tests that may be done to diagnose an autoimmune disorder may include:
- Antinuclear antibody tests
- Autoantibody tests
- CBC
- C-reactive protein (CRP)
- Erythrocyte sedimentation rate (ESR)
http://www.myositis.org/storage/documents/General_Research/geoepidemiology.pdf
Viral, bacterial or parasitic infectious agents may induce an aberrant immune response, (many mesh implanted patients have chronic infections)
http://www.ncbi.nlm.nih.gov/pubmed/22235042
Human adjuvant disease induced by foreign substances: a new model of ASIA (Shoenfeld's syndrome). Vera-Lastra O1, Medina G, Cruz-Dominguez Mdel P, Ramirez P, Gayosso-Rivera JA, Anduaga-Dominguez H, Lievana-Torres C, Jara LJ.
Patients presented with defined autoimmune diseases as well as with non-specific autoimmune manifestations. Illegal injection of these substances could lead to serious local and systemic complications, even to death. These cases represent another model of Autoimmune/inflammatory Syndrome Induced by Adjuvants (ASIA). The use of these substances should be prohibited.
PMID: 22235042 [PubMed - indexed for MEDLINE]
http://wwwnc.cdc.gov/eid/article/10/11/04-0367_article.htm#areautoimmunediseasescausedbyinfections
Why Are Autoimmune Diseases So Prevalent in Women? Abstract :Autoimmune diseases affect approximately 8% of the population, 78% of whom are women. The reasons for the high prevalence in women are unknown, but circumstantial evidence links autoimmune diseases with preceding infections. Animal models of autoimmune diseases have shown that infections can induce autoimmune disease. For example, coxsackievirus B3 (CB3) infection of susceptible mice results in inflammation of the heart (myocarditis) that resembles myocarditis in humans. The same disease can be induced by injecting mice with heart proteins mixed with adjuvant(s), which indicates that an active infection is not necessary for the development of autoimmune disease. We have found that CB3 triggers autoimmune disease in susceptible mice by stimulating elevated levels of proinflammatory cytokines from mast cells during the innate immune response. Sex hormones may further amplify this hyperimmune response to infection in susceptible persons, which leads to an increased prevalence of autoimmune diseases in women.....
The best evidence so far that infections can induce autoimmune diseases comes from animal models. In most animal models of autoimmunity, including myocarditis, disease has been transferred to naïve animals with autoimmune cells (splenocytes or T cells), autoantibodies (7), or both, which provides compelling evidence that infections induce autoimmune diseases by immune-mediated mechanisms.
http://www.ncbi.nlm.nih.gov/pubmed/22235043
“patient illustrates an example of ASIA (Autoimmune Syndrome Induced by Adjuvants), as her disease appeared following exposure to an adjuvant stimulus, with 'typical', although not well-defined, autoimmune manifestations.”
http://lup.sagepub.com/content/21/2/118.extract
Autoimmune Syndrome Induced by Adjuvants
http://drclaudiamiller.com/2012/05/08/medical-implants-initiators-of-tilt/ Prescription drugs have unique codes the government can use to track problems. But implanted devices? No such luck..........
And there’s an unexplored dimension to the implant question: Implants are “xenobiotics,” petrochemical products that pose particular concern for people who may be more chemically susceptible......Over a decade ago, in 1999, along with co-author Thomas J. Prihoda, PhD, I reported on a group of patients who received implants and subsequently developed chronic health problems and chemical intolerances that they had never experienced before...........
Although inserting implants certainly differs from inhaled exposures to pesticides or air contaminants in a sick building, for susceptible individuals it seems like the body doesn’t care whether the exposure is exogenous (like air pollutants) or endogenous, like an implant. The consequences can be similar — chronic, multi-system symptoms and intolerances for foods, alcoholic beverages, caffeine, everyday chemicals like cleaning agents, engine exhaust, fragrances, and even medications like antibiotics or antidepressants. Once people become ill, not just the implants, but everyday exposures like these can trigger symptoms and perpetuate illness.............implant companies intentionally excluded women with autoimmune histories from their studies because of concern that the women would have medical complications that would jeopardize getting FDA approval.”
http://informahealthcare.com/doi/abs/10.1080/08916930701574331
Earlier investigations from our laboratory revealed increased oxidative damage in SLE patients. Therefore, we hypothesized that oxidative by-products, such as hydroxyl radical (√OH), could lead to neoantigens like √OH damaged human serum albumin (HSA), which could in turn initiate autoimmunity in SLE.
http://www.nlm.nih.gov/medlineplus/ency/article/000821.htm
COMPLICATIONS DUE TO AN ALTERED IMMUNE RESPONSE
An efficient immune response protects against many diseases and disorders. An inefficient immune response allows diseases to develop. Too much, too little, or the wrong immune response causes immune system disorders. An overactive immune response can lead to the development of "autoimmune diseases," in which antibodies form against the body's own tissues.
Complications from altered immune responses include:
- Allergy or hypersensitivity
- Anaphylaxis
- Autoimmune disorders
- Graft versus host disease
- Immunodeficiency disorders
- Serum sickness
- Transplant rejection ( is it a big leap to suspect implant rejection ? too ? )
http://www.ncbi.nlm.nih.gov/books/NBK27155/
- Specific adaptive immune responses to self antigens can cause autoimmune disease
- Autoimmune diseases can be classified into clusters that are typically either organ-specific or systemic
- Susceptibility to autoimmune disease is controlled by environmental and genetic factors, especially MHC genes
- The genes that have been associated with the development of systemic lupus erythematosus provide important clues to the etiology of the disease
- Antibody and T cells can cause tissue damage in autoimmune disease
- Autoantibodies against blood cells promote their destruction
- The fixation of sublytic doses of complement to cells in tissues stimulates a powerful inflammatory response
- Autoantibodies against receptors cause disease by stimulating or blocking receptor function
- Autoantibodies against extracellular antigens cause inflammatory injury by mechanisms akin to type II and type III hypersensitivity reactions
- Environmental cofactors can influence the expression of autoimmune disease
- The pattern of inflammatory injury in autoimmunity can be modified by anatomical constraints
- The mechanism of autoimmune tissue damage can often be determined by adoptive transfer
- T cells specific for self antigens can cause direct tissue injury and have a role in sustained autoantibody responses
- Autoantibodies can be used to identify the target of the autoimmune process
- The target of T cell-mediated autoimmunity is difficult to identify owing to the nature of T-cell ligands
Go to:
13-3 Susceptibility to autoimmune disease is controlled by environmental and genetic factors,......
So far, susceptibility to autoimmune disease has been most consistently associated with MHC genotype. Human autoimmune diseases that show associations with HLA type are shown in Fig. 13.3. For most of these diseases, susceptibility is linked most strongly with MHC class II alleles, but in some cases there are strong associations with particular MHC class I alleles.
As HLA genotyping has become more exact through the sequencing of HLA alleles, disease associations that were originally discovered through HLA serotyping using antibodies have been defined more precisely. For example, the association between IDDM and the DR3 and DR4 alleles is now known to be due to their tight genetic linkage to DQβ alleles that confer susceptibility to disease. Indeed, disease susceptibility is most closely associated with polymorphisms at a particular position in the DQβ amino acid sequence. The most abundant DQβ amino acid sequence has an aspartic acid at position 57 that is able to form a salt bridge across the end of the peptidebinding cleft of the DQ molecule. By contrast, the diabetic patients in Caucasoid populations mostly have valine, serine, or alanine at that position and thus make DQ molecules that lack this salt bridge (Fig. 13.6). The nonobese diabetic (NOD) strain of mice, which develops spontaneous diabetes, also has a serine at that position in the homologous MHC class II molecule, known as I-Ag7.
A further very important factor in disease susceptibility to SLE is the hormonal status of the patient. Indeed, many autoimmune diseases show a strong sex bias (see Fig. 13.3). Where a bias towards disease in one sex is observed in experimental animals, castration or the administration of estrogen to males usually normalizes disease incidence between the two sexes. Furthermore, many autoimmune diseases that are more common in females show peak incidence in the years of active child bearing, when production of the female sex hormones estrogen and progesterone is at its greatest. A thorough understanding of how these genetic and hormonal factors contribute to disease susceptibility might allow us to prevent the autoimmune response.
SummaryFor a disease to be defined as autoimmune, the tissue damage must be shown to be caused by an adaptive immune response to self antigens. Autoimmune diseases can be mediated by autoantibodies and/or by auto-reactive T cells, and tissue damage can result from direct attack on the cells bearing the antigen, from immune-complex formation, or from local inflammation.
Copyright © 2001, Garland Science.
Bookshelf ID: NBK27155
http://www.answers.com/topic/immune-systemUsually, the immune system is extremely effective in performing its work of defending the body, but sometimes an error occurs in this highly complex system, and it can lead to terrible mistakes. The result can be an allergic reaction, which can be as simple as a case of the sniffles and as serious as a fatal condition. Or the error can manifest as an autoimmune disorder, such as lupus, in which the body rejects its own constituents as foreign invaders. Read more: http://www.answers.com/topic/immune-system#ixzz2vhMuE1Sp
The reasons why the immune system becomes dysfunctional are not well understood, but most researchers agree that a combination of genetic, environmental, and hormonal factors plays into autoimmunity. They also speculate that certain mechanisms may trigger it. First, a substance normally restricted to one part of the body, and therefore not usually exposed to the immune system, is released into other areas, where it is attacked. Second, the immune system may mistake a component of the body for a similar foreign component. Third, cells of the body may be altered in some way, by drugs, infection, or some other environmental factor, so that they are no longer recognizable as "self" to the immune system. Fourth, the immune system itself may be dysfunctional, for instance, because of a genetic mutation.
Read more: http://www.answers.com/topic/immune-system#ixzz2vhNXb0OA
http://www.hindawi.com/journals/ad/2014/437231/
Autoimmune Diseases Volume 2014 (2014), Article ID 437231, 18 page http://dx.doi.org/10.1155/2014/437231
Review Article : A Potential Link between Environmental Triggers and AutoimmunityAristo Vojdani
Generally, to clear infections the innate immune cells can upregulate costimulatory molecules and produce a mixture of pro- and anti-inflammatory cytokines such as interleukin-1-beta (IL-1β), IL-12, transforming growth factor-beta (TGF-β), IL-23, tumor necrosis factor-alpha (TNF-α), and IL-6 that regulate the adaptive arm of the immune system. However, a dysregulated immune response to environmental triggers, such as pathogens, microbiota, or toxins, can initiate a chronic inflammatory response through activation of T-helper-1 (Th1), Th17, and TNF-α and the production of IL-17, IL-22, interferon-gamma (IFN-γ), and IL-21, resulting in inflammation, antibody production and tissue injury [6]. Therefore, a dysregulated adaptive immune system is at the core of the pathogenesis of autoimmune and other immune-mediated diseases. Hyperactivation of innate immune response affects the adaptive immune response as well as development effector T and B cells. Paired with defects in the regulatory T cells, this results in the breakdown of immune homeostasis and the development of autoimmunity [7].
bacterial bio-films :
https://attachment.fbsbx.com/file_download.php?id=834871916557617&eid=ASt_IlUPDpTsS9VkVTdBb6iuDQclP0j3lmNqmixLukcvhngusZPd9rzD2mqGqERHXfM&inline=1&ext=1411789675&hash=ASuR6jbpiUs_iAGc
http://cdn.intechopen.com/pdfs-wm/12815.pdfPrevention of Biofilm Associated Infections and Degradation of Polymeric Materials used in
Biomedical Applications , Peter Kaali, Emma Strömberg and Sigbritt Karlsson
Royal Institute of Technology, Sweden
....... the degradation mechanisms and the factors influencing the degradation of medical polymers are discussed. The factors that should be controlled are the biofilm formation and the prevention of infections caused by the microorganisms that usually generate intensive body reactions. Means to modify the polymeric materials by incorporating antimicrobial agents into the bulk of the polymer or right onto the surface as a coating is presented.
benefit over risk:
http://www.ajog.org/article/S0002-9378%2811%2901018-0/pdfSummary
One-year objective and functional outcomes of a randomized clinical trial of vaginal mesh for prolapsePresented orally at the 31st annual meeting of the American Urogynecologic Society, Long Beach, CA, Sept. 30-Oct. 2, 2010.
Andrew I. Sokol, MD, Cheryl B. Iglesia, MD, Bela I. Kudish, MD, Robert E. Gutman, MD, David Shveiky, MD, Richard Bercik, MD, Eric R. Sokol, MDReceived: April 21, 2011; Received in revised form: July 6, 2011; Accepted: August 4, 2011; Published Online: August 12, 2011
http://weill.cornell.edu/news/news/2015/06/pelvic-organic-prolapse-procedures-with-mesh-increase-leading-to-age-based-complications.html
Despite FDA warnings that a synthetic mesh used to treat a weakening of the female pelvis's walls can cause infection, pain, and disease recurrence, surgeons are increasing their use of the device. What's more, when compared to not using mesh, younger patients who undergo surgery with mesh for pelvic organ prolapse (POP) are more likely to have a repeat surgery the following year, and older patients are more likely to have complications while they're in the hospital, according to new research from Weill Cornell Medical College.
http://www.ncbi.nlm.nih.gov/pubmed/22239416
BJOG. 2012 Feb;119(3):354-60. doi: 10.1111/j.1471-0528.2011.03231.x.
Development of de novo prolapse in untreated vaginal compartments after prolapse repair with and without mesh: a secondary analysis of a randomised controlled trial.Withagen MI1, Milani AL, de Leeuw JW, Vierhout ME.
Author information
AbstractOBJECTIVE:To compare the de novo prolapse rate in the untreated vaginal compartments following conventional vaginal prolapse repair and tension-free vaginal mesh repair.
DESIGN:Secondary analysis of a randomised controlled trial.
SETTING:Thirteen centres in the Netherlands.
POPULATION:Women with recurrent pelvic organ prolapse stage II or higher.
METHODS:Random assignment to either conventional vaginal native tissue repair or vaginal mesh insertion.
MAIN OUTCOME MEASURES:Primary outcome: de novo pelvic organ prolapse stage II or higher in the untreated vaginal compartments at 12 months after surgery. Secondary outcomes: de novo pelvic organ prolapse at and beyond the hymen, de novo prolapse beyond the hymen and prolapse domain scores of the Urogenital Distress Inventory.
RESULTS:At 12 months ten of 59 women (17%) in the conventional group versus 29 of 62 women (47%) in the mesh group were diagnosed with a de novo pelvic organ prolapse stage II or higher in the untreated compartment (P < 0.001, odds ratio 4.3, 95% confidence interval 1.9-10.0). Additional apical support to a mesh-augmented anterior repair significantly reduced the de novo prolapse rate. Women with a de novo prolapse in the mesh-treated group demonstrated significantly higher mean bother scores on the domain genital prolapse of the Urogenital Distress Inventory score (13.1 ± 24.2) compared with those without de novo prolapse (2.9 ± 13.9) (P = 0.03).
CONCLUSION:Mesh-augmented prolapse repair in only one vaginal compartment is associated with a higher de novo prolapse rate in the untreated compartments compared with conventional vaginal native tissue repair in women with recurrent pelvic organ prolapse.
© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.
biocompatibility:
http://en.wikipedia.org/wiki/Biocompatibility
Five definitions of biocompatibility
- "The ability of a material to perform with an appropriate host response in a specific application", Williams' definition.[7]
- "The quality of not having toxic or injurious effects on biological systems".[8]
- "Comparison of the tissue response produced through the close association of the implanted candidate material to its implant site within the host animal to that tissue response recognised and established as suitable with control materials" - ASTM
- "Refers to the ability of a biomaterial to perform its desired function with respect to a medical therapy, without eliciting any undesirable local or systemic effects in the recipient or beneficiary of that therapy, but generating the most appropriate beneficial cellular or tissue response in that specific situation, and optimising the clinically relevant performance of that therapy".[9][10]
- "Biocompatibility is the capability of a prosthesis implanted in the body to exist in harmony with tissue without causing deleterious changes".[11]
Biocompatibility: Meeting a Key Functional Requirement of Next ...tpx.sagepub.com/content/36/1/70.full
by MN Helmus - 2008 - Cited by 37 - Related articles The array of polymeric, biologic, metallic, and ceramic biomaterials will be reviewed with respect to their biocompatibility, which has traditionally been viewed as ...
http://www.landesbioscience.com/iu/Helmus_9781587064562.pdf
Potential complications will vary with a device and its application. Biodegradation and infection become increasingly important in longer term applications such as central venous catheters and permanently implanted devices. Because of the large surface area in extra-corporeal circuits, activation of biologic pathways, such as the coagulation, fibrinolytic, and complement pathways, may be magnified. Patients who are treated by extracorporeal methods (e.g., hemodialysis) are repeatedly exposed to leachable plasticizers and sterilant residuals.
http://books.google.ca/books?id=7L8EK4mU0ikC&pg=PA384&lpg=PA384&dq=Polymeric+Biomaterials,+Volume+1+introduced+into+the+body+of+a+specific+individual+without+exciting+a+destructive+reaction%E2%80%9D&source=bl&ots=wtrTEvTRDe&sig=PM4aDpJlpk3Qobqh3gOsuy_rt4s&hl=en&sa=X&ei=mrMYU9_eIo_roATNxIGICQ&ved=0CCwQ6AEwAA#v=onepage&q=Polymeric%20Biomaterials%2C%20Volume%201%20introduced%20into%20the%20body%20of%20a%20specific%20individual%20without%20exciting%20a%20destructive%20reaction%E2%80%9D&f=false
“Biocompatibility refers to the ability of a biomaterial to perform its desired function with respect to a medical therapy without eliciting and undesirable or systemic effect in the recipient beneficiary of that therapy, but generating the most appropriate beneficial cellular or tissue response in that specific situation and optimizing the clinically relevant performance of that therapy.”
“the capacity of a foreign synthetic material to be introduced into the body of a specific individual without exciting a destructive reaction”
“mutual tolerance” where both the patient and implant tolerate each other without any negative response the effects of long term implants
“remember materials are tested in an environment that does not resemble the conditions they encounter after implantation”
cytotoxioity...the effect on cells ..identify and quantify degradation products residues of ethylene oxide should be investigated .
Sensitization and irritation can only be tested invivo, effects of degradation and must be done for all medical devices...
without involvement of immunological mechanism is a localized irritation......chronic systemic toxicity measurements are required for permanent implants ......presence of dead cells or large numbers of inflammatory cells indicates toxicity of the implant "
http://www.ncbi.nlm.nih.gov/pubmed/21455703
Mesh biocompatibility: effects of cellular inflammation and tissue remodelling.Junge K1, Binnebösel M, von Trotha KT, Rosch R, Klinge U, Neumann UP, Lynen Jansen P.
Author information
AbstractMesh biocompatibility is basically determined by the foreign body reaction (FBR). In contrast to physiological wound healing and scar formation, the FBR at the host-tissue/biomaterial interface is present for the lifetime of the medical device. The cellular interactions at the mesh/tissue interface proceed over time ending up in a chronic inflammatory process. The time course of the FBR has been studied extensively and consists of three crucial steps that are protein absorption, cell recruitment and, finally, fibrotic encapsulation and extracellular matrix formation. Each of these steps involves a complex cascade of immune modulators including soluble mediators and various cell types. Recent research has focused on the cellular and molecular interactions of the distinct phases of the FBR offering a new basis for therapeutical strategies. The highly dynamic process of the FBR is considerably influenced by the biomaterial composition. Modifications of the type of polymer, the material weight, the filament structure and the pore size are realized and have substantial effects on the in vivo biocompatibility. Moreover, modern mesh technology aims to utilize the available implants as carrier systems for bioactive drugs. Studies in animal models account for the efficiency of these drugs that aim to reduce mesh-related infections or to minimize FBR by influencing inflammation or extracellular matrix remodelling. A thorough understanding of the molecular mechanisms of FBR provides a sophisticated background for the development of new biomaterials at least as carrier systems for bioactive reagents to reduce inflammation and to improve clinical outcome.
biofilms:
http://cdn.intechopen.com/pdfs-wm/12815.pdf
Prevention of Biofilm Associated Infections and
Degradation of Polymeric Materials used in
Biomedical Applications
Peter Kaali, Emma Strömberg and Sigbritt Karlsson
Royal Institute of Technology,
Sweden
1. Introduction
Biomedical polymers have a wide variety of applications for external and internal use.
Similar criteria must be fulfilled by biomedical polymeric materials used as internal or
partly internal (invasive) devices, where the polymer gets in contact with the human
environment. The material needs to be biocompatible, neutral to the human body and have
to express excellent stability and resistance against tissues, cells, enzymes and different body
fluids. The body response to the polymer can be acceptance or rejection and depending on
the location of the material, these responses are influenced by different factors. Besides the
body response, the microbiological effect and biofilm formation on the internal medical
devices are of great importance. If biofilm adheres to the surface it can initiate a degradation
process of the material, and due to the high concentration of microorganisms, infections and
health related problems can be caused. The biocompatibility of polymers does not only
depend on the chemical structure, the capability of microbes and the body environment to
adhere or also initiate the degradation inside the human body is highly structure dependant.
Once degradation occurs, along with the migration of additives and low molecular weight
compounds, the polymer loses its biocompatibility and stability, which can lead to the
failure of the device or could cause health related issues. Therefore the understanding of the
different degradation processes that may occur inside the human body due to blood, tissue
or biofilm interaction is very important. This chapter gives an overview on the mechanism
of biofilm formation and adherence to surfaces, and means to characterize and determine its
presence. Furthermore, the effect and the role of body-polymer interaction, the degradation
mechanisms and the factors influencing the degradation of medical polymers are discussed.
The factors that should be controlled are the biofilm formation and the prevention of
infections caused by the microorganisms that usually generate intensive body reactions.
Means to modify the polymeric materials by incorporating antimicrobial agents into the
bulk of the polymer or right onto the surface as a coating is presented
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112322/
In vivo biofilm on the surface of a surgical mesh implant by A Reśliński 2009 - Cited by 5 - Related articles
This paper presents the course of the disease in the case of biofilm formation on the surface of an implanted surgical mesh. Antimicrobial therapy and partial ...the use of synthetic materials carries the risk of infection and biofilm formation
carcinogenic risk:
http://www.ncbi.nlm.nih.gov/pubmed/23604537 ( sorry, link broken, please copy and paste into your browser search )
Mesh: cancer......Hernia. 2014 Dec;18(6):897-901. doi: 10.1007/s10029-013-1083-x. Epub 2013 Apr 19.Mesh cancer: long-term mesh infection leading to squamous-cell carcinoma of the abdominal wall.Birolini C1, Minossi JG, Lima CF, Utiyama EM, Rasslan S.Author information AbstractPURPOSE: It is recognized that chronic inflammation can cause cancer. Even though most of the available synthetic meshes are considered non-carcinogenic, the inflammatory response to an infected mesh plays a constant aggression to the skin. Chronic mesh infection is frequently the result of misuse of mesh, and due to the challenging nature of this condition, patients usually suffer for years until the infected mesh is removed by surgical excision.
METHODS: We report two cases of squamous-cell carcinoma (SCC) of the abdominal wall, arising in patients with long-term mesh infection.
RESULTS: In both patients, the degeneration of mesh infection into SCC was presumably caused by the long-term inflammation secondary to infection. Patients presented with advanced SCC behaving just like the Marjolin's ulcers of burns. Radical surgical excision was the treatment of choice. The involvement of the bowel played an additional challenge in case 1, but it was possible to resect the tumor and the involved bowel and reconstruct the abdominal wall using polypropylene mesh as onlay reinforcement, in a single stage operation. He is now under adjuvant chemotherapy. The big gap in the midline after tumor resection in case 2 required mesh bridging to close the defect. The poor prognosis of case 2 who died months after the operation, and the involvement of the armpit, groin and mesenteric nodes in case 1 shows how aggressive this disease can be.
CONCLUSION: Infected mesh must be treated early, by complete excision of the mesh. Long-standing mesh infection can degenerate into aggressive squamous-cell carcinoma of the skin.
PMID:23604537 [PubMed - in process
carcinogenisis and foreign body reaction:
http://onlinelibrary.wiley.com/doi/10.1002/ijc.23125/pdf
reactive oxygen species derived from inflammatory cells are one of the most important genotoxic mediators to accelerate the process... Foreign-body-induced carcinogenesis in human ....... foreign bodies can induce tumors in human. ......
In the same line of the evidence, foreign bodies incorporated into body for medical reasons or accidentally appear to lead to inflammation-based carcinogenesis..........Inflammatory environments due to the existence of foreign body cause a variety of biological responses........
http://monographs.iarc.fr/ENG/Monographs/vol74/mono74.pdf
WORLD HEALTH ORGANIZATION :evaluation of the carcinogenic risk of chemicals to humans involving the production of critically evaluated monographs on individual chemicals........
4B.7 Polypropylene
4B.7.1 Subcutaneous administration Rat: A group of 70 E3 rats [sex and age not specified] was given subcutaneous
implants of eight polypropylene discs (20 mm diameter, 2 mm thick). The experiment was terminated after 14 months, when 35 animals were still alive. A total of 55 local fibrosarcomas were produced, the first appearing after seven months. In another
group of 60 rats, which was given a total of 480 implants, the discs were removed eight months after the implantation. The experiment was terminated at 14 months,when 41 animals were still alive. Two fibrosarcomas were observed at the ninth
month, and 32 further local tumours were detected during the following five months (Vollmar & Ott, 1961). [The Working Group noted that no controls were included in these experiments.]A group of 67 rats [sex, strain and age unspecified] was given a combination of implantation of discs (a total of 536 implants) and X-irradiation (3 × 200 rad, two to three weeks after implantation) which led to reduced survival. When the experiment was terminated after 14 months, a total of 34 local tumours had been found and 18 animals were still alive. After implantation of a total of 560 samples of polypropylene powder to 70 rats, the first local fibrosarcoma was found at 11 months. When the experiment was terminated after 14 months, four rats had developed local sarcomas and 35 were still alive (Vollmar & Ott, 1961). [The Working Group noted that nocontrols were included in these experiments.]A group of 20 male Wistar rats, six weeks of age, was given subcutaneous implants of a thin polypropylene film (15 × 15 × 0.1 mm). No local tumour was found among 18 animals that survived for more than 11 months, during a 28-month observation period (Imai & Watanabe, 1987).A group of 50 Wistar male rats [age unspecified] was given subcutaneous implants of a medical-grade polypropylene film (20 × 10 × 1 mm); 17/50 survivors developed
malignant tumours at the site of implantation during the 24-month experimental period. Most of the tumours were diagnosed as malignant fibrous histiocytoma, and the latency period was 512 ± 133 days. One fibroma occurred among 50 sham-operated controls (Nakamura et al., 1997).
Chemical sensitivity to implants :
http://drclaudiamiller.com/2012/05/08/medical-implants-initiators-of-tilt/
"there’s an unexplored dimension to the implant question: Implants are “xenobiotics,” petrochemical products that pose particular concern for people who may be more chemically susceptible. ... To determine whether you may be at increased risk of developing TILT, you can take the QEESI to gauge your own susceptibility or to document changes in your symptoms and intolerances as a consequence of an implant or its removal. Many individuals do report improvement in symptoms once their implants are removed. As for the FDA, the regulatory agency has done poorly in its role of gathering scientific data about the safety of implants. Dr. Diana Zuckerman, president of the National Research Center for Women and Families, a research and education group, told an expert panel of the FDA in 2011 that some breast implant manufacturers had failed to carry out the FDA’s own recommended studies of post-implant patients. One of the FDA’s chief scientists, Dr. William Maisel, later acknowledged shortcomings when questioned by the New York Times."
chronic immune response:
http://www.biotechniques.com/BiotechniquesJournal/2011/October/Tissue-engineering-tools-for-modulation-of-the-immune-response/biotechniques-322251.html?pageNum=2
Tissue engineering tools for modulation of the immune response
Ryan M. Boehler, John G. Graham, and Lonnie D. Shea
.........While synthetic scaffolds can be produced without introducing these signals, synthetic polymers, their degradation products, or the associated provisional matrix can activate the complement cascade (8). Phagocytic cells are attracted to the implant by the chemokines released from the provisional matrix and surrounding cells. These cells adhere to the material, and if the material is large, may undergo a “frustrated phagocytosis” that can lead to increased secretion of inflammatory products (5)........Macrophages have also been shown to adopt an M2 phenotype after phagocytosis of debris (14). A quick resolution (two weeks) to this chronic cellular presence at the tissue-material interface is often compatible with implant acceptance while persistence of a large immune cell presence often indicates infection and/or rejection of the implant (5).........The immune response has the potential to cause extensive secondary damage; however, more recent approaches have attempted to modulate the immune response in a manner than can more effectively promote regeneration at the site of injury. The following sections describe strategies employed to modulate the inflammatory response toward regeneration rather than repair.........Reducing the immune response to implanted biomaterials may be achieved by choosing materials that are intrinsically immune-inert, or modifying material properties to prevent recognition by the immune system as summarized in Table 1........The beneficial effects of the immune response on regeneration may be retained using localized delivery systems, which do not impact the entire immune system and have the potential to selectively recruit specific immune cells or create a local anti-inflammatory microenvironment that influences the phenotype of infiltrating cells.
Conclusions:Regenerative medicine offers tremendous potential for the replacement of functional tissues. Technologies based on biomaterials, drug, protein and gene delivery, and cell transplantation provide the fundamental tools, with the objective of creating an environment that supports the development of progenitor cells into functional tissues. While these technologies to control the environment are critical, the immune response is also an essential consideration. Each technological component has the potential to elicit an immune response that can derail regeneration and lead to fibrosis. However, appropriate application of these technologies has the potential to turn the immune response into an asset for regeneration, leading to the differentiation of cells toward a more regenerative and less inflammatory phenotype. Furthermore, recruitment or delivery of immune cells can be employed as a means to tolerize the host to prevent rejection of transplanted cells. Taken together, these technologies have broad implications for numerous applications of biomaterials in medicine, and also in emerging area of cell-based therapies.
chronic inflammation:
http://link.springer.com/article/10.1007/s00423-006-0073-1
Chronic inflammation and oxidative stress in the genesis and perpetuation of cancer: role of lipid peroxidation, DNA damage, and repair: Helmut Bartsch, Jagadeesan Nair
Abstract: Background and aims: Chronic inflammation, induced by biological, chemical, and physical factors, was associated with increased risk of human cancer at various sites. Chronic inflammatory processes induce oxidative/nitrosative stress and lipid peroxidation (LPO), thereby generating excess reactive oxygen species (ROS), reactive nitrogen species (RNS), and DNA-reactive aldehydes. Miscoding etheno- and propano-modified DNA bases are generated inter alia by reaction of DNA with these major LPO products. Steady-state levels of LPO-derived (etheno-) DNA adducts in organs affected by persistent inflammatory processes were investigated as potential lead markers for assessing progression of inflammatory cancer-prone diseases.......ConclusionPersistent oxidative/nitrosative stress and excess LPO are induced by inflammatory processes in a self-perpetuating process and cause progressive accumulation of DNA damage in target organs. Together with deregulation of cell homeostasis, the resulting genetic changes act as driving force in chronic inflammation-associated human disease pathogenesis. Thus steady-state levels of DNA damage caused by ROS, RNS, and LPO end products provide promising molecular signatures for risk prediction and potential targets and biomarkers for preventive measures.
http://www.ncbi.nlm.nih.gov/pubmed/17893868
Chronic inflammation and oxidative stress in human carcinogenesis.Federico A1, Morgillo F, Tuccillo C, Ciardiello F, Loguercio C.
Author information
AbstractA wide array of chronic inflammatory conditions predispose susceptible cells to neoplastic transformation. In general, the longer the inflammation persists, the higher the risk of cancer. A mutated cell is a sine qua non for carcinogenesis. Inflammatory processes may induce DNA mutations in cells via oxidative/nitrosative stress. This condition occurs when the generation of free radicals and active intermediates in a system exceeds the system's ability to neutralize and eliminate them. Inflammatory cells and cancer cells themselves produce free radicals and soluble mediators such as metabolites of arachidonic acid, cytokines and chemokines, which act by further producing reactive species. These, in turn, strongly recruit inflammatory cells in a vicious circle. Reactive intermediates of oxygen and nitrogen may directly oxidize DNA, or may interfere with mechanisms of DNA repair. These reactive substances may also rapidly react with proteins, carbohydrates and lipids, and the derivative products may induce a high perturbation in the intracellular and intercellular homeostasis, until DNA mutation. The main substances that link inflammation to cancer via oxidative/nitrosative stress are prostaglandins and cytokines. The effectors are represented by an imbalance between pro-oxidant and antioxidant enzyme activities (lipoxygenase, cyclooxygenase and phospholipid hydroperoxide glutathione-peroxidase), hydroperoxides and lipoperoxides, aldehydes and peroxinitrite. This review focalizes some of these intricate events by discussing the relationships occurring among oxidative/nitrosative/metabolic stress, inflammation and cancer.
c) 2007 Wiley-Liss, Inc.
PMID: 17893868 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/16857722Oxidative and nitrative stress caused by subcutaneous implantation of a foreign body accelerates sarcoma development in Trp53+/- mice.Tazawa H1, Tatemichi M, Sawa T, Gilibert I, Ma N, Hiraku Y, Donehower LA, Ohgaki H, Kawanishi S, Ohshima H.
Author information
Abstract: Chronic inflammation is a recognized risk factor for human cancer at various sites because of persistent oxidative and nitrative tissue damage. Trp53+/- mice show the predisposition to tumor development, such as sarcomas and lymphomas, compared with Trp53+/+ mice. We investigated the effects of chronic inflammation, especially oxidative and nitrative stress, induced by subcutaneous implantation of a plastic plate (10 x 5 x 1 mm) as a foreign body on tumorigenesis in Trp53+/- and Trp53+/+ mice. The plastic plates were implanted at the age of about 11 weeks. Thirty out of 38 Trp53+/- mice (79%) developed sarcomas around the implant (mean time of tumor appearance was 45.8 +/- 12.0 weeks of age), whereas only one of 10 Trp53+/+ mice with an implant (10%) developed a tumor, at 56 weeks. No sarcomas developed at a sham-operation site. Two of 10 Trp53+/- mice with no implant (20%) also developed three sarcomas spontaneously at 77, 81 and 84 weeks. Increased immunostaining for markers of oxidative and nitrative stress (8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-nitroguanine and 3-nitrotyrosine) and expression of inducible nitric oxide synthase in tumor cells and inflammatory cells were detected in implant-induced sarcomas compared with spontaneous sarcomas in Trp53+/- mice. Furthermore, p53 loss of heterozygosity was observed in 26 out of 29 implant-induced sarcomas (90%). These results indicate that implanted foreign bodies significantly enhanced sarcoma development in Trp53+/- mice, and this may be associated with increased oxidaive and nitrative stress. Loss of the remaining wild-type p53 allele and loss of p53 function appears to be, at least in part, underlying molecular mechanisms during the development of sarcomas at the implantation site in Trp53+/- mice. Such implant-induced sarcoma development in Trp53+/- mice could be useful for studying molecular mechanisms and developing new strategies for chemoprevention in human carcinogenesis induced by chronic inflammation and/or foreign bodies.
PMID: 16857722 [PubMed - inde
http://tpx.sagepub.com/content/38/1/96.full
Oxidative DNA Damage: Oxidative DNA damage is a major source of the mutation load in living organisms, with more than one hundred oxidative DNA adducts (purine, pyrimidine, and the deoxyribose backbone) having been identified (Lu et al. 2001; von Sonntag 1987;Dizdaroglu 1992; Demple and Harrison 1994). The estimated frequency of oxidative DNA damage in human cells is 104 lesions/cell/day (Fraga et al. 1990; Lu et al. 2001). Being highly reactive, the hydroxyl radical is the predominant ROS that targets DNA (Lu et al. 2001). Hydrogen peroxide, a precursor to hydroxyl radical, is less reactive and more readily diffusible and thus more likely to be involved in the formation of oxidized bases through Fenton and Haber-Weiss reactions (Guyton and Kensler 1993;Barber and Harris 1994). ROS-induced DNA damage can result in single- or double-strand breakage, base modifications, deoxyribose modification, and DNA cross-linking. Cell death, DNA mutation, replication errors, and genomic instability can occur if the oxidative DNA damage is not repaired prior to DNA replication (Marnett 2000; J. P. Cooke 2003; Klaunig and Kamendulis 2004; Valko et al. 2006).
http://cancerres.aacrjournals.org/content/54/7_Supplement/1929s.short
Inflammation, Chromosomal Instability, and Cancer: The Schistosomiasis Model1
- Miriam P. Rosin2, Wagida A. Anwar, and Amanda J. Ward Author Affiliation, Epidemiology Division, British Columbia Cancer Agency, Vancouver, British Columbia, Canada [M. P. R., A. J. W.], and Department of Community, Environmental and Occupational Medicine, Ain Shams University, Cairo, Egypt [W. A. A.]
Abstract: Evidence is accumulating in support of a role for reactive oxygen species in the etiology of cancer. Inflammatory cells, such as neutrophils, macrophages, and eosinophils, are an important endogenous source of oxygen radicals. Stimulation of these cells by tumor promoters or by foreign bodies (parasites, bacteria, etc.) causes the release of reactive oxygen species. Laboratory studies have shown that genetic damage and neoplastic transformation are induced in vitro in cells cocultured with activated inflammatory cells. We have recently begun to study the role of inflammatory reactions in inducing genetic damage in a human population. This paper describes our initial studies of Egyptian patients infected with Schistosoma haematobium. This infection induces chronic inflammation and irritation in the urinary bladder and is associated with increased cancer at this site. We describe a recently completed population study that shows that infected individuals have elevated levels of genetic damage in their bladders, as measured by the exfoliated cell micronucleus test. Treatment that kills the parasite also reduces the micronucleus frequencies. We also explore the hypothesis that altered sensitivity of clones of cells in these patients to reactive oxygen species could be a force that drives the development of neoplasia by facilitating clonal expansion. Evidence is presented for the possible involvement of loci on chromosome 11 in controlling the level of chromosomal breakage caused by oxidative damage. We have shown that bladder carcinoma cells are sensitive to micronucleus induction by promoter-activated neutrophils and that they can be protected from this damage by insertion of a normal chromosome 11. Further work is in progress to define the source of chromosomal breakage in schistosomiasis patients and to begin to develop an understanding of the host factors protecting bladder cells in these individuals from genetic damage
http://onlinelibrary.wiley.com/doi/10.1002/ijc.23125/full
Keywords:
- inflammation;
- ROS;
- foreign body;
- carcinogenesis;
- tumor progression
Jump to…Abstract
Foreign-body-induced carcinogenesis is a traditional, maybe old, way of understanding cancer development. A number of novel approaches are available today to elucidate cancer development. However, there are things we learn from the old, and thus I bring out some examples of various clinical cases and experimental models of foreign-body-induced tumorigenesis. What is notable is that the foreign bodies themselves are unrelated to each other, whereas commonly underlying in them is to induce inflammatory reaction, especially stromal proliferation, where those exogenous materials are incorporated and undigested. Such foreign-body-induced carcinogenesis is also recognized in the step of tumor progression, the final step of carcinogenesis that tumor cells acquire malignant phenotypes including metastatic properties. And the phenomenon is universally observed in several cell lines of different origins. In this review I would like to show the evidence that tumor development and progression are accelerated inevitably by inflammation caused from foreign bodies, and that reactive oxygen species derived from inflammatory cells are one of the most important genotoxic mediators to accelerate the process. © 2007 Wiley-Liss, Inc.
chronic pain:
http://theses.gla.ac.uk/2579/1/2009PageMD.pdf
Severe chronic pain is one of the most serious long-term problems that can occur following inguinal hernia repair. Population based studies and randomised clinical trials indicate that around 30% of patients have some form of pain, while 3% have severe pain at one year following hernia repair 144, 192. The reason for such pain is not clear. There may be intraoperative factors that contribute to this pain, such as nerve and/ or tissue injury and the use of the biomaterials. In the latter context a recent study has indicated that the type of
material, rigid versus smooth may affect postoperative pain and recovery after laparoscopic inguinal hernia repair 193. There is also some evidence from trials of abdominal wall closure that absorbable suture materials cause less chronic pain when compared with nonabsorbable ones 194, 195
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183551/...patients came to the office after surgical procedures for stress urinary incontinence and were seen for chronic pelvic pain after TOT-O procedures that had been previously performed 6 months to 3 years prior to being seen. No pain had been noted prior to the surgical procedure performed for stress urinary incontinence.
http://dare.uva.nl/document/194631
severe persistent groin pain after uncomplicated TVT-O, in which magnetic resonance imaging and electromyography
did not reveal the cause. We concluded that the tapementrapped or cut through peripheral branches of the
obturator nerve. ... chance that damage to the obturator nerve is reversible, although it is importantto counsel patients with similar pathology that recovery cantake long and may be only partial. Keywords Obturator nerve damage .Pain.Tension-free vaginal tape–obturator.Therapy
severe persistent groin pain after uncomplicated TVT-O, in which magnetic resonance imaging and electromyography did not reveal the cause. We concluded that the tape entrapped or cut through peripheral branches of the obturator nerve.
https://www.researchgate.net/profile/Vincent_Letouzey
Article
Managing chronic pelvic pain following reconstructive pelvic surgery with transvaginal mesh.Anthony N Gyang, Jessica B Feranec, Rakesh C Patel, Georgine M Lamvu
Minimally Invasive Gynecology, 3004 17th Street, St Cloud, FL, 34769, USA, .
International Urogynecology Journal (Impact Factor: 2.17). 11/2013; DOI:10.1007/s00192-013-2256-ySource: PubMed
ABSTRACT In 2001, the US Food and Drug Administration (FDA) approved the first transvaginal mesh kit to treat pelvic organ prolapse (POP). Since the introduction of vaginal mesh kits, some vaginal meshes have been associated with chronic pelvic pain after reconstructive pelvic floor surgery. Pelvic pain results in between 0 % and 30 % of patients following transvaginal mesh placement. Common causes of chronic pelvic pain include pelvic floor muscle spasm, pudendal neuralgia, and infection. Paucity of data exists on the effective management of chronic pelvic pain after pelvic reconstructive surgery with mesh. We outline the management of chronic pelvic pain after transvaginal mesh placement for reconstructive pelvic floor repair based on our clinical experience and adaptation of data used in other aspects of managing chronic pelvic pain conditions.
http://Inflammation causes some postsurgical neuropathies ( info considering multiple surgeries to remove mesh are common)
Date: September 22, 2010 Source: Mayo Clinic Summary: A new study found that nerve inflammation may cause the pain, numbness and weakness following surgical procedures that is known as post-surgical neuropathy: A new Mayo Clinic study found that nerve inflammation may cause the pain, numbness and weakness following surgical procedures that is known as postsurgical neuropathy. The development of postsurgical neuropathies is typically attributed to compression or stretching of nerves during surgery. This new research shows that, in some cases, the neuropathy is actually caused by the immune system attacking the nerves and is potentially treatable with immunosuppressive drugs. The study was published in this month's issue of Brain. Postsurgical neuropathy is an uncommon complication of surgery. Peripheral nerves are the extensive network of nerves that link the brain and spinal cord (the central nervous system) to all other parts of the body. When damaged by stretching, compression or inflammation, the peripheral nerve injury can interfere with communication between the brain and the rest of the body (muscles and sensation are controlled by the nerve). Individuals with postsurgical neuropathy may experience loss of sensation, pain and muscles weakness. "It is important that a person with postsurgical inflammatory neuropathy receive a diagnosis and treatment quickly. Understanding the role of inflammation in these patients' neuropathy can lead to appropriate immunotherapy and improvement of neurological symptoms and impairments," says P. James Dyck, M.D., a Mayo Clinic neurologist and senior author of this study. As part of the research, Dr. Dyck and a team of Mayo Clinic researchers selected 23 patients who developed neuropathy within 30 days of a surgical procedure. According to Dr. Dyck, the neuropathy of these 23 patients did not make sense in terms of being caused by stretching or compression because the nerves damaged were usually in a different part of the body from the surgical site or the neuropathy occurred at least a few days after the surgery was over. The surgical procedures were orthopedic, abdominal, chest or dental. All the patients received a nerve biopsy, of which 21 demonstrated increased inflammation. Seventeen patients were treated over a three-month period with immunotherapy, and in all cases with follow-up the neuropathy impairments improved. "This is exciting for patients because it allows for appropriate identification and accurate treatment of postsurgical neuropathy. Without showing inflammation on the nerve biopsies, we would have been unable to know the cause of the neuropathy," says Nathan Staff, M.D., Ph.D., a Mayo Clinic neurologist and the first author of this study. "It is logical for patients to believe that it was the surgeon's fault that they developed a neuropathy because it occurred after the surgery," says Dr Dyck. "However, in these cases, we have strong evidence that the neuropathies were not the surgeon's fault but were caused by the immune system attacking the nerves." Other members of the Mayo Clinic research team included JaNean Engelstad, Christopher Klein, M.D., Kimberly Amrami, M.D., Robert Spinner, M.D., Peter Dyck, M.D., Mark Warner, M.D., and Mary Warner, M.D. Story Source: The above story is based on materials provided by Mayo Clinic. Note: Materials may be edited for content and length. Journal Reference: N. P. Staff, J. Engelstad, C. J. Klein, K. K. Amrami, R. J. Spinner, P. J. Dyck, M. A. Warner, M. E. Warner, P. J. B. Dyck. Post-surgical inflammatory neuropathy. Brain, 2010; DOI: 10.1093/brain/awq252 Cite This Page: MLA APA Chicago Mayo Clinic. "Inflammation causes some postsurgical neuropathies." ScienceDaily. ScienceDaily, 22 September 2010. <www.sciencedaily.com/releases/2010/09/100922111432.htm>.
complications:
http://www.urocenterofnewyork.com/upload/iblock/026/2013.10%20Salvage%20Surgery%20after%20Failed%20Treatment%20of%20Synthetic%20Mesh%20Sling%20Complications.pdf
Salvage Surgery after Failed Treatment of Synthetic Mesh
Sling Complications ,Jerry G. Blaivas,* Rajveer S. Purohit,† James M. Weinberger,‡,§ Johnson F. Tsui,kJyoti Chouhan,k Ruhee Sidhu{ and Kamron Saleem ........ only 28%of patients with pain considering the salvage operation a success.
http://www.ncbi.nlm.nih.gov/pubmed/18801499
There were 928 MEDLINE citations for sling and complications, 279 for sling and complications and bladder, and 68 for sling and complications and voiding dysfunction. The reported complication rates ranged from 4.3% to 75.1% for retropubic and 10.5% to 31.3% for transobturator mid urethral slings. Complications included bladder perforation, hemorrhage, bowel injury, vaginal extrusion, de novo urgency and urge incontinence, urinary tract infections and voiding dysfunction. Retropubic mid urethral slings led to a higher occurrence of complications such as bladder perforation and hematoma. In addition, the retropubic approach resulted in serious complications such as bowel injury, major vascular injury and death. Groin pain was more common after the transobturator approach. Experimental studies indicated that the potential mechanisms for sling complications may include vaginal dissection, denervation injury and bladder remodeling.
CONCLUSIONS:Mid urethral slings result in bothersome complications which should not be minimized. Awareness of these complications should encourage improvements in patient counseling as well as further investigation of the underlying mechanisms. Decreasing complications should be considered an important outcome for future clinical studies of mid urethral slings.
http://books.google.co.nz/books?id=dIYVK2CyXLgC&pg=PA87&lpg=PA87&dq=was+vaginal+mesh+experimental%3F&source=bl&ots=p2W_xJbm0i&sig=PrR6qMIVpWZtwpMfW0k0GrDV7A&hl=en&sa=X&ei=PpMdU4XiHc7OkwWK7YH4BQ&redir_esc=y#v=onepage&q=was%20vaginal%20mesh%20experimental%3F&f=false
Complications of Female Incontinence and Pelvic Reconstructive Surgery By Howard B. Goldman
http://tvtno.org/signs-symptoms-side-effects/explain-range-of-side-effects/
- Mesh Erosion through the urethra, vaginal wall, bowel and bladder
- Depression, anxiety
- Bleeding
- Constant Urinary Tract Infections
- Constant vaginal infections
- Deep tissue infections
- Vaginal Swelling
- Du novo urgency and voiding dysfunction
- Bladder stones
- Pain in buttocks and thighs
- Vaginal Discharge
- Retropubic Hematoma
- Abscess
- Swelling in the stomach
- Difficult and painful defecation/buttock pain sitting
- Allergic reactions to the mesh
- Obturator Nerve Damage
- Septicemia
- Shrinkage of the vagina due to scar tissue caused by mesh removal
- Fournier’s Gangrene
- Injury to lilac vessel’s
- Perforation of the Bowl and Bladder
- Pulmonary Embolism
- Death
http://urology.ucla.edu/body.cfm?id=657
UCLA Urology has become a referral center for patients who have suffered from mesh related complications due to vaginal and sling mesh. To date, we have performed over 400 mesh complication surgeries. Mesh complications are highly complex issues and each individual is treated according to their unique problem. If you are suffering from a mesh-related issue, we may be able to help you.
http://www.icsoffice.org/Documents/ViewDocumentVersions.aspx?DocumentID=671
"We should all thank Donald Ostergard for emphasizing what are really far more serious problems than erosions, chronic pain, fistulae, dyspareunia, urinary and fecal incontinence. Large mesh insertions cause formation of large concrete-like depositions of collagen. Collagen shrinks and contracts with time. SO these collagen depositions may stretch and distort organs, nerves, indeed, anything in their path. Nor should trauma from the instruments be ignored. Don and Gunnar Lose were prescient in their comments in 1999, and 2002 where they proposed zero tolerance for life-threatening complications.. Int.Urogynecol J 1999;10(6):351-2.) Int.Urogynecol J, 2002; 13:1-3. Maybe we should discuss the instruments as well. The MAUDE data base of the FDA is a good resource which really needs to be included as a reference point......
One concern, leaving space for future as yet unreported complications. A formal classification may be too limiting. The initiative itself is brilliant, and sorely needed. Would a less formal classification, more in the nature of a resource be easier to handle? It could be added or subtracted to with ease. For example, already patients are presenting with urinary retention years after midurethral slings, a result of collagen contraction. How do we classify long-term effects when we do not know what they are? We need to leave space......Complications refer to untoward outcomes not directly related to the purpose of the surgery.
http://www.hindawi.com/journals/ogi/2013/356960/
Obstetrics and Gynecology International
Volume 2013 (2013), Article ID 356960, 7 pages
Review Article
The Role of Vaginal Mesh Procedures in Pelvic Organ Prolapse Surgery in View of Complication RiskDavid R. Ellington and Holly E. Richter . Complications of Vaginal Mesh Procedures in the Treatment of Pelvic Organ Prolapse. A wide spectrum of potential complications exist with the use of transvaginal mesh in POP surgery. Rare, but severe complications, including death, fistula formation, and mesh erosion into adjacent organs, have been reported in the MAUDE database. Three of seven deaths were related directly to mesh placement procedures and included two bowel perforations and one hemorrhage [7]. Vesicovaginal fistula formation after the use of synthetic transvaginal mesh in the anterior compartment as well as retrovesical hematoma formation and mesh erosions not simply through the vaginal epithelium but into the bladder has also been reported [8, 9]. Though relatively rare, a thorough understanding of these morbid complications and the subsequent management of them is imperative to the consideration of synthetic transvaginal mesh use in POP surgery.
http://commonhealth.wbur.org/2011/11/surgery-under-scrutiny-what-went-wrong-with-vaginal-mesh
Complications Rising .....Last year, a clinical trial comparing vaginal mesh for prolapse to traditional surgery using women’s own ligaments for repair was stopped early due to excessive complications, with more than 15 percent of patients experiencing mesh erosion. The New York Times quoted the lead author of the report, Dr. Cheryl B. Iglesia, director of female pelvic medicine and reconstructive surgery at Washington Hospital Center in the District of Columbia, saying: “The bottom line is not only there were more complications, but the mesh didn’t prove any better than traditional surgery.”
http://commonhealth.wbur.org/2011/11/surgery-under-scrutiny-what-went-wrong-with-vaginal-mesh
"The doctor who placed the mesh in me is a former president of AUGS (American Urogynecological Society). He has a reputation for being an incredibly skilled surgeon. However, 6.5 years later, I have massive erosion and extrusion, both into my vagina and rectum, leaving me with essentially no native tissue over the apex of my vagina. The mesh is infected back past the obturator fascia on the right side. I have permanent pudendal nerve damage from how he placed it. It isn't the skill of the doctor. IT IS THE DEVICE AND THE DELIVERY SYSTEM.
All three urogyns who have seen me in the past five months know the surgeon who placed the mesh. All three are **shocked** to see me in their office because most people believe just as you say, that the trouble is due to "non-expert" surgeons. According to the current president of AUGS, Dr. Peggy Norton, who examined me in September 2012, I represent the beginning of an onslaught of mesh complications because if *I* developed complications even though I had one of the most talented urogyns in the world place the mesh, then it means ANYONE can develop complications."
http://onlinelibrary.wiley.com/doi/10.1111/j.1447-0756.2008.00820.x/full
Safety of Trans Vaginal Mesh procedure: Retrospective study of 684 patients, Fréderic Caquant, Pierre Collinet, Philippe Debodinance, Juan Berrocal, Olivier Garbin, Claude Rosenthal, Henri Clave,Richard Villet, Bernard Jacquetin, Michel Cosson Article first published online: 21 AUG 2008
DOI: 10.1111/j.1447-0756.2008.00820.x ........
our study shows a certain number of late post-surgical complications after insertion of strengthening synthetic vaginal implants (prosthetic expositions and prosthetic retractions). These retrospective results will soon be compared to a prospective study.
http://www.prnewswire.com/news-releases/signs-your-transvaginal-mesh-has-failed-from-tvm-resource-for-women-243930501.html
SAN FRANCISCO, Feb. 6, 2014 /PRNewswire-iReach/ -- Any woman who has had transvaginal mesh implant surgery is at risk for serious health complications. As advised by the FDA in a communication released in 2011, not only are health risks posed to women who have had this treatment, the effectiveness of treatment with the medical device compared to traditional options has not been made clear.
FDA Warns: 'Serious Complications' Arise From Vaginal Mesh Implants
Serious complications associated with surgical mesh for transvaginal repair of [pelvic organ prolapse] are not rare. Furthermore, it is not clear that transvaginal [pelvic organ prolapse] repair with mesh is more effective than traditional non-mesh repair in all patients [...] and it may expose patients to greater risk.
For more information about serious complications from vaginal mesh implants, please visit http://healthland.time.com/2011/07/13/fda-warns-serious-complications-arise-from-vaginal-mesh-implants/.
With thousands of surgical mesh repair procedures being performed on women each year, it is important that patients are fully aware of the warning signs to identify when there is a potential problem with their implant.....Pelvic Mesh Riskier Than Thought: FDA
http://www.laborie.ca/articles/complications-of-synthetic-mid-urethral-slingsCOMPLICATIONS OF SYNTHETIC MID-URETHRAL SLINGSC. Twiss, S. Raz
Christian O. Twiss, MD, received his MD from New York University School of Medicine, in New York, New York. He is finishing a fellowship in female urology, reconstructive surgery, and urodynamics at the University of California, Los Angeles and will be joining the faculty at the University of Arizona, Division of Urology as an assistant professor and director of female urology and urodynamics. Shlomo Raz, MD, holds an MD from the University of Montevideo, Uruguay. He is a professor in the Department of Surgery, Division of Urology at the University of California, Los Angeles School of Medicine. He is on the editorial boards of numerous publications, is the author of Atlas of Transvaginal Surgery and is a co-author of Female Urology, Urogynecology and Voiding Dysfunction.
Due to its efficacy, safety, and relative simplicity, the synthetic mid-urethral sling procedure has emerged as one of the mainstays of surgical therapy for female stress urinary incontinence. The transobturator approach to placing mid-urethral slings has recently been marketed as safer than the retropubic approach due to avoidance of entry into the retropubic space. However, accumulated experience has demonstrated that significant complications are possible with both techniques. The purpose of this review is to summarize the rates, etiology, and management of the most common complications encountered with synthetic mid-urethral slings and to compare, based on recent evidence, complication rates of the retropubic and transobturator approaches to sling placement.........
Postoperative vaginal erosions are another problem with synthetic slings. Metaanalyses 10,17 of randomized trials comparing retropubic with transobturator synthetic slings fail to demonstrate a significant difference in vaginal erosion rates between the two techniques. Large case series 2,23,25,26 of TVT and SPARC-sling procedures report that vaginal erosions are rare, occurring in 0.2%–1.8% of cases. While some authors 27 have suggested slightly higher rates of vaginal erosions with transobturator slings, this may reflect the high erosion rates (6.1%–20%) noted to occur with the Mentor ObTape kit, 28-30 which has subsequently been removed from the market. More recently, a large French registry 20 of 984 TVT-O (inside-out transobturator approach for TVT) procedures reported a postoperative vaginal erosion rate of 0.6%, a figure within the range found in the large TVT and SPARC series.
degradation:
Degradation of polypropylene in vivo: A microscopic analysis of meshes explanted from patients
- Vladimir V. Iakovlev1,*,
- Scott A. Guelcher2 and
- Robert Bendavid3,*
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112322/
Degradation, infection and heat effects on polypropylene mesh for pelvic implantation: what was known and when it was known Donald R. Ostergard Author information ► Article notes ► Copyright and License information ►
Abstract: Many properties of polypropylene mesh that are causative in producing the complications that our patients are experiencing were publishedin the literature prior to the marketing of most currently used mesh configurations and mesh kits. These factors were not sufficiently taken into account prior to the sale of these products for use in patients. This report indicates when this information was available to both mesh kit manufacturers and the Food and Drug Administration. Keywords: Polypropylene, Mesh, Degradation, Heat, Infection
https://gupea.ub.gu.se/bitstream/2077/24978/1/gupea_2077_24978_1.pdf
.... polymers can be degraded by heat, oxidation, light, ionic radiation, hydrolysis and mechanical shear, and by pollutants such as carbon monoxide, sulphur dioxide, nitrogen oxide and ozone (Ravve, 2000). This causes the polymer to get brittle, to fragment into small pieces and to release degradation products. Different degradation mechanisms exist and which of them that will dominate depends on the polymer type. Chain scission involves breaking the chemical bonds in the polymer molecule, and is often random,
but for some polymers it proceeds at the polymer end chains and the initial monomers are broken off, a process called depolymerisation (Alger, 1997; Braun, 2005).
http://www.iso.org/iso/iso_catalogue/catalogue_tc/catalogue_detail.htm?csnumber=44050
ISO 10993‑13:2010 considers only those degradation products generated by a chemical alteration of the finished polymeric device. It is not applicable to degradation of the device induced during its intended use by mechanical stress, wear or electromagnetic radiation or biological factors such as enzymes, other proteins and cellular activity.
http://www.ics.org/Documents/ViewDocumentVersions.aspx?DocumentID=671
On page 8, first paragraph, perhaps you should include low surface area of the mesh, since this is also known to be important for bacterial attachment. The larger the surface area the more space is available for bacteria to attach and, also, the more inflammatory reaction that is elicited. In addition, you might want to mention that the use of an inert mesh is important---since polypropylene degrades in the human body, and polyester does not the search for the best mesh must continue...........In the next paragraph, you mention "rejection". Unless you have evidence that there is an immunological reaction to the mesh, you might want to just say "erosion". I think rejection should be reserved for a true immunological reaction. True rejection may be occurring secondary to the release of polypropylene degradation products. However, I don’t know of any scientific evidence as yet that this is occurring. I think "rejection" is used elsewhere in this draft.
http://books.google.ca/books?id=saRhsXmgf0UC&pg=PA27&lpg=PA27&dq=antioxidant+and+stabilizer+additives+in+polypropylene+resins+for+medical+use&source=bl&ots=YbyuUgGev5&sig=-O2w1tmfRoBpjmk503iP-PaxcLw&hl=en&sa=X&ei=v4YbU9yYLdjtoASOx4CICg&ved=0CG4Q6AEwBw#v=onepage&q=antioxidant%20and%20stabilizer%20additives%20in%20polypropylene%20resins%20for%20medical%20use&f=false
Polypropylene: The Definitive User's Guide and Databook By Clive Maier, Theresa Calafut..........degradation, free radicals
http://www.ncbi.nlm.nih.gov/pubmed/6474110
Scand J Work Environ Health. 1984 Jun;10(3):163-9.
Analytical, occupational and toxicologic aspects of the degradation products of polypropylene plastics.Frostling H, Hoff A, Jacobsson S, Pfäffli P, Vainiotalo S, Zitting A.
AbstractThermooxidative degradation of polypropylene (PP) at close to the industrial processing temperatures was studied with thermogravimetric analysis, infrared spectroscopy, and gas chromatography-mass spectrometry (GC-MS). GC-MS allowed identification of 47 volatile degradation products. Formaldehyde, acetaldehyde, alpha-methylacrolein, acetic acid, and acetone were the major products. Antioxidants markedly slowed down the degradation of polypropylene and the evolution of the degradation products. The relative amounts of the oxidized products were mostly independent of the degradation temperature or the type of antioxidant. Measurements in the plastics industry revealed low airborne concentrations of individual volatile products. The concentration of aerosols, which infrared analysis showed to resemble paraffin fumes, was significant and probably the most important hygienic hazard. The biochemical parameters (the consumption of protecting sulfhydryl groups and the effects on foreign compound metabolism) indicated that the degradation products are biologically reactive, affecting the balance of normal metabolism in exposed animals.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769140/
.........3. Oxidation Degradation; Oxidation is another mechanism that causes polymers to degrade. For polymers implanted in human body, this is usually due to the oxidation by peroxides produced by the body. Production of the oxidative agents is part of the defense action by the human immune system that always tries to remove foreign materials through inflammation reactions and other processes. This section will discuss three points, production of oxidative agents by biological systems, chemistry of oxidation reactions of polymers, and kinetics of oxidation degradation.3.1. Reactive Oxidative Agents in TissuesUpon implantation, inflammatory cells migrate to the implant site, starting a series of events ranging from acute to chronic reactions. For biomaterials that are “accepted” by the body, a capsule forms around the implant which is primarily composed of collagen with foreign body giant cells (FBGC), fibroblasts, and perhaps macrophages inside. The FBGCs are formed by the fusion of macrophages that are differentiated from monocytes (from the acute inflammation reactions). The FBGCs and macrophages produce peroxides that are eluted near the implants with an intent to degrade them (Figure 14)......
In oxidation reactions, free radicals are critical, but they act as initiators or reactive intermediate species. The net reaction is between the polymers and oxygen; the products can be water, CO2, hydroxyl chain ends, or carboxylic acid chain ends. A general chemical reaction mechanism includes initiation, free radical proliferation, chain transfer, chain breakup, and termination.
6. Effects of Degradation Products on the Body: An important question to consider is the effect of the polymer degradation products on the body. Hydrolysis produces carboxylic acid and/or hydroxyl chain ends. Hydroxyl groups may be further oxidized later. Oxidation reactions may produce many different species, but they are usually aldehydes, ketones or carboxylic acids. Whether these entities are detrimental to device performance depends on the specific species, amounts, generation rates, and contacting tissues. An implant of small size and slow degradation rate may trigger very mild biological reactions compared to a large implant made of the same material. This issue of concern is biocompatibility. A polymer that does not react with its surroundings (that is, one that would be termed as “inert”) is usually reasonably biostable and may have less biocompatibility concerns. However, it must be remembered that biocompatibility can only be determined under the conditions of use. That is, in the form of the device that will be implanted, and in the tissue it will be used in. Hence, one must be careful in making generalizations about material compatibility.
When a material degrades, it is no longer the material that was originally proven biocompatible. Because of this, the makers of implantable materials must consider stability as one of their biocompatibility criteria. One of the likely scenarios is that the formation of small chain carboxylic acids leads to local pH changes that cause an inflammatory response. The ability of the body to tolerate such a situation depends on a number of things including whether the body can dilute the response through either homeostasis or by simply moving the offending species to somewhere they can be further degraded or flushed out via the kidneys. Rather obviously, if the degrading material is captured in a confined space (such as in a partially healed implant) it may more easily cause an inflammatory reaction.....The abundance of water and the relentless onslaught of the body to attack foreign materials means that the performance of implanted polymers in the body depends upon not only the choice of the polymer, but also subtle things like processing, additives and mechanical stress under the usage conditions. Hence, it is very important that hydrolysis and oxidation reactions must be well understood when considering use of such materials for implantable use.
http://www.imc.cas.cz/sympo/MoDeSt2012/pdf/OC_092-Yang.pdf
In contrast, various oxidative products could be found in aged polypropylene (PP) [2]. 2) Migration of additives in polymer can be detected.
http://cdn.intechopen.com/pdfs-wm/12815.pdf
Prevention of Biofilm Associated Infections and Degradation of Polymeric Materials used in
Biomedical Applications , Peter Kaali, Emma Strömberg and Sigbritt Karlsson Royal Institute of Technology, Sweden
....... the degradation mechanisms and the factors influencing the degradation of medical polymers are discussed. The factors that should be controlled are the biofilm formation and the prevention of infections caused by the microorganisms that usually generate intensive body reactions. Means to modify the polymeric materials by incorporating antimicrobial agents into the bulk of the polymer or right onto the surface as a coating is presented.
http://books.google.ca/books?id=FU4Kq7liHJgC&pg=PA328&lpg=PA328&dq=degradation+products+of+implanted+medical+devices+materials&source=bl&ots=R9vGyRdbvn&sig=TYVJ9HADNQYJx8pwgCFU9tLoa0k&hl=en&sa=X&ei=yl8-U9PBCI_gsASjo4Jw&ved=0CCwQ6AEwADgU#v=onepage&q=degradation%20products%20of%20implanted%20medical%20devices%20materials&f=false
Corrosion and Degradation of Implant Materials edited by B. C. Syrett, A. Acharya...the jury would be asked to decide.......
diagnostic imaging to "see" mesh location, condition, breakage or migration:
http://www.bkmed.com/Collateral/Documents/BK-Medical/Clinical/BG0462-A.pdf
......In fact, we were starting discussions with mesh manufacturers in the United States requesting that they start to weave into
the mesh a material that would allow visualization of the mesh on MRI, when I attended the Treviso International Congress on Ultrasonographic Imaging of Pelvic Floor Disorders XI. At that time, I saw first hand how well ultrasound imaging can visualize the surgical meshes that are being used to treat prolapse and incontinence......At this time, I am imaging women with any mesh complications post-operatively with ultrasound. I have seen women referred to our practice with mesh easily visualized in the bladder and urethra. In addition, we have found mesh that has detached from the vagina, and this represents a technical failure of the surgery as opposed to a new prolapse. The position and integrity of a mesh is clearly illustrated using high resolution endovaginal ultrasound.
dyspareunia: (painful sexual intercourse)
http://link.springer.com/article/10.1007/s00192-011-1384-5
This study describes the incidence, risk factors, and treatments of graft erosion, wound granulation, and dyspareunia as adverse events following vaginal repair of pelvic organ prolapse with non-absorbable synthetic and biologic graft materials.MethodsA systematic review in Medline of reports published between 1950 and November 2010 on adverse events after vaginal prolapse repairs using graft materials was carried out.
Results: One hundred ten studies reported on erosions with an overall rate, by meta-analysis, of 10.3%, (95% CI, 9.7 – 10.9%; range, 0 – 29.7%; synthetic, 10.3%; biological, 10.1%). Sixteen studies reported on wound granulation for a rate of 7.8%, (95% CI, 6.4 – 9.5%; range, 0 – 19.1%; synthetic, 6.8%; biological, 9.1%). Dyspareunia was described in 70 studies for a rate of 9.1%, (95% CI, 8.2 – 10.0%; range, 0 – 66.7%; synthetic, 8.9%; biological, 9.6%).
http://www.ics.org/Documents/ViewDocumentVersions.aspx?DocumentID=671
Lacerations of the husband by defect healings are of clinical and legal importance, they are nor classified. Simple complications like failure, OAB or, rather frequent obstruction because of wrong technique and placement are frequent and should be included in future classifications.
http://www.marketwatch.com/story/life-care-solutions-group-the-vaginal-mesh-debacle-is-more-complicated-then-the-hip-settlement-2013-11-20
The injuries caused by the transvaginal mesh debacle are more diverse than of the defective hip implant. Injuries from the mesh cause a variety of problems including erosions, recurrent infections, recurrent incontinence, recurrent prolapse, painful sexual intercourse related to pelvic myofascial pain, painful sexual intercourse related to pudendal neuralgia, ano-rectal pain related to pelvic myofascial pain, ano-rectal pain related to pudendal neuralgia, vulvodynia related to pelvic myofascial pain, vulvodynia related to pudendal neuralgia, and obturator neuralgia. All of these pain syndromes and functional problems may coexist and each patient is truly unique regarding how these pain generators affect mobility, sexual function, bowel evacuation, and bladder excretion.
http://www.ncbi.nlm.nih.gov/pubmed/21477026/
Painful love-"hispareunia" after sling erosion of the female partner.Mohr S1, Kuhn P, Mueller MD, Kuhn A.Author information
Abstract INTRODUCTION:Sling erosion/extrusion is a complication after suburethral sling insertion for female stress urinary incontinence that occurs in approximately 6% of patients. Symptoms may include vaginal discharge, infections, postcoital bleeding, and alterations of the sexual function. Little is known about the effect of sling erosion on the sexual function of the male partner.
AIM:The aim of this study was to determine male sexual function in partners of women who had undergone sling insertion for stress urinary incontinence and who developed sling erosion postoperatively.
MAIN OUTCOME MEASURES:Main outcome measures were the Brief Male Sexual Function Inventory (BMSFI) and visual analog scale (VAS) scores. METHODS:Male partners of patients who presented with sling erosion for various reasons were addressed and asked to fill in the BMSFI and assess sexual pain using the VAS before and 6 months after the sling erosion of their female partners was treated. Participants gave informed consent and those who had undergone prostate surgery during the past 12 months were excluded. For statistical analyses, SPSS version 10.0 (SPSS Inc., Chicago, IL, USA) was used.
RESULTS:Thirty-two males were included in the study and produced a full set of data. VAS scores as a measurement for "hispareunia" improved from a median score of 8 before to a median score of 1 after intervention. Some domains of male sexual function (sexual interest, sexual drive, ejaculation, and erection) were significantly improved whereas the strength of erection, problems with ejaculation, and problems with lack of interest were not statistically significantly changed.
CONCLUSIONS:Changes of male sexual function and particularly pain after sling insertion in their female partners may be due to sling exposure. Sexual interest and drive may be negatively influenced. Male dyspareunia is a complaint that can be treated effectively by correcting the sling exposure.© 2011 International Society for Sexual Medicine.
erosion/ erosion rates :
http://onlinelibrary.wiley.com/doi/10.1111/1471-0528.12085/full#.U5PckN4U4YM.facebook
(thinning vaginal walls are often blamed for mesh erosion, this study indicates that mesh implantation iteslf may be the cause of thinning vaginal walls)
Vaginal morphology and connective tissue remodelling were adversely affected by mesh implantation. Implantation with a stiffer mesh resulted in increased collagenase activity, decreased collagen and elastin content, and increased GAG content, indicating a negative impact on the structural integrity of vagina. Future studies investigating the functional impact of mesh on the vagina as well as the molecular mechanisms resulting in the degenerative changes are needed to further corroborate these findings.
http://link.springer.com/article/10.1007/s00192-011-1460-x/fulltext.html
International Urogynecology JournalIncluding Pelvic Floor Dysfunction© The International Urogynecological Association 2011
10.1007/s00192-011-1460-x Mentors in Urogynecology, Reflections on my career as a urogynecologist
Donald R. Ostergard1 (1)Division of Urogynecology and Reconstructive Surgery, Department of Obstetrics, Gynecology and Women’s Health, University of Louisville, School of Medicine, 550 South Jackson St., Second Floor, Louisville, KY 40202, USA
Donald R. Ostergard Email: [email protected] ........ Controversy is now rampant in the polymer mesh field. I have had concerns about this from the beginning, having had prior experience using such prostheses for stress incontinence with a 21% vaginal erosion rate and abscesses being found upwards of 5 years later. Resected specimens revealed the presence of marked bacterial colonization [1]. When surgical procedures for pelvic prolapse repair were first introduced, I warned against them. When the first kit containing mesh was offered for sale, disaster ensued. Prote-Gen® (Microvasive Urology) was ultimately removed from the market because of many erosions and urethrovaginal fistulae. The US Food and Drug Administration (FDA) ruled that the product was adulterated and misbranded and agreed with the recall. Interestingly, I was asked to review the data for this product before it was offered for sale by a venture capital company. The data were weak, and I advised against their financial involvement in what was to be the first incontinence surgical procedure for sale. Microvasive certainly did the right thing in recalling the product. The mesh used was polyester-coated with “pressure-injected” bovine collagen.The FDA clears products by the 510k process. This process involves a predicate that must be similar to the same planned usage and technological characteristics as the new product. The TVT® used Prote-Gen® as its predicate, even though it is a polypropylene mesh product and not polyester with a bovine collagen coating. All of the currently marketed mesh kits are descendants of this adulterated product..............
http://www.kristin-jenkins.com/pages/medical/breakoutpages/KJ_uro_corcos.html
Topic: Is there a difference between mid urethral slings? By Kristin JenkinsQUEBEC CITY, Que: -- Knitted polypropylene appears to be the material of choice for sub-urethral implantation in the female patient with stress urinary incontinence (SUI).........
Dr. Jacques Corcos warned delegates to Urogynecology Quebec 2007 that many of the sub-urethral sling products currently on the market have not undergone adequate clinical testing. Dr. Corcos is director of the urology department at Jewish General Hospital, Montreal, and professor of urology at McGill University.
Obtape, which initially showed promised as an effective treatment alternative to TVT, was pulled from the market following reports of significantly higher rates of erosion compared to other trans-obturator tapes. Dr. Corcose noted that tapes such as Obtryx and Arix, which are distributed to urologists worldwide, have not been formally studied and don’t appear to have been investigated for safety and efficacy.
Dr. Corcos urged colleagues to carefully assess how easily any bio-prosthetic material can be removed. “This is a basic surgical principle,” he noted, that must be observed given “…the significant difficulty of surgical removal in the setting of deep space infections.”
Although partial resection is the recommended surgical approach for vaginal erosions, “the possibility of leaving behind infected portions of mesh is real,” said Dr. Corcos. As a result, many women may present with late-onset deep space infections that ultimately require radical debridement.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721525/
Erosion and extrusion of mesh are common and troublesome complications .....Use of Type I mesh has demonstrated consistent success with similar rates of vaginal extrusion regardless of the technique for placement. Extrusion rates of 0.4-4.8% for TVT, 1-10.5% for SPARC and 0-6.7% for the transobturator Monarc have been reported.[19–23] A second transobturator sling that utilized a fusion-welded, thermally bonded, nonwoven, nonknitted polypropylene mesh (Ob-Tape™, Mentor Corp, Santa Barbara, CA) had significantly higher rates of extrusion ranging from 10-20%.[22,24–26]Comparable extrusion rates of 0-19% have been reported with sacrocolpopexy.[27,28] New techniques (Apogee™ and Perigee™ (American Medical Systems, Minnetonka, MN) and Gynecare Prolift (Ethicon, Sommerville, NJ) have been developed that place polypropylene via the transobturator or transvaginal approach in the repair of anterior vaginal wall prolapse or vaginal vault prolapse. These techniques have shown promising early results, but intermediate and long-term data on rates of erosion and extrusion are yet to be presented.[29,30] ...Erosion into the urinary tract mandates complete removal of mesh regardless of mesh type [Figure 3].
http://www.hindawi.com/journals/ogi/2013/356960/
A wide spectrum of potential complications exist with the use of transvaginal mesh in POP surgery. Rare, but severe complications, including death, fistula formation, and mesh erosion into adjacent organs, have been reported in the MAUDE database. Three of seven deaths were related directly to mesh placement procedures and included two bowel perforations and one hemorrhage [7]. Vesicovaginal fistula formation after the use of synthetic transvaginal mesh in the anterior compartment as well as retrovesical hematoma formation and mesh erosions not simply through the vaginal epithelium but into the bladder has also been reported [8, 9]
http://www.ics.org/Documents/ViewDocumentVersions.aspx?DocumentID=671
". Unless you have evidence that there is an immunological reaction to the mesh, you might want to just say "erosion". I think rejection should be reserved for a true immunological reaction. True rejection may be occurring secondary to the release of polypropylene degradation products. However, I don’t know of any scientific evidence as yet that this is occurring. I think "rejection" is used elsewhere in this draft.
http://www.hoajonline.com/journals/pdf/2052-6210-1-4.pdf
According to several surveys, the rate of vaginal erosion after vaginal wall repair ranges from 3.8% to 20% [65,66],
The disadvantages to using these mesh devices from the erosion and extrusion rates of material. This type of complication is reported in the literature and occurs in 2.8% to 17.3% of cases [69]. Several factors are believed to contribute to mesh erosions. These include a poor healing environment, which is influenced by blood flow, infections, foreign body reactions, and mesh characteristics [70]. Deffiqux et al., [66] compared the erosion rate between different types of mesh and concluded that there were no any differences.
experts in mesh removal:
https://www.uclahealth.org/provider/shlomo-raz-md
Shlomo Raz, MD Specialty:Urology Department Affiliation:Urology Hospital Affiliation:
Ronald Reagan UCLA Medical Center
http://vsuinstitute.com/
Dr. Veronikis: for more information you can email him at [email protected]. He does request the following information via fax (314-251-4492) or email: Index operative report and any subsequent surgical procedures as well as the operative implant log. This information allows him quickly to understand each individual lady’s symptoms and needs. You can expect a rather rapid response from Dr. V as he checks his emails throughout the day.You can learn more about Dr. Dionysios K. Veronikis’ practice location and view mesh removal pictures at www.drveronikis.com and patient ratings at his Healthgrades page here Healthgrades/Veronikis.
http://urology.ucla.edu/body.cfm?id=657
UCLA Urology has become a referral center for patients who have suffered from mesh related complications due to vaginal and sling mesh. To date, we have performed over 400 mesh complication surgeries. Mesh complications are highly complex issues and each individual is treated according to their unique problem. If you are suffering from a mesh-related issue, we may be able to help you
Larissa V. Rodriguez, MD Affiliations: Professor, Department of Urology, David Geffen School of Medicine at UCLA
Address:UCLA Department of Urology 200 Medical Plaza, Suite 140 Los Angeles, CA 90095 Phone: (310) 794-0206
Fax: (310) 794-0211 Email: [email protected]
Biography:Dr. Larissa V. Rodríguez's clinical research focuses on outcomes of vaginal surgery, quality of life as it relates to pelvic floor disorders, and the pathophysiology and treatment of interstitial cystitis. In the laboratory she is pursuing investigations in the genetics and pathophysiology of vaginal prolapse, as well as applications of stem cell and tissue engineering for the treatment of incontinence and reconstruction of the urinary tract. In addition, she has an interest in the role of stress on urinary symptoms.
She has been a recipient of numerous research grants including being in the first cohort of recipients of the American of Geriatrics Society Jahnigen Career Development Scholars Award, NIH K12 career development award and being principal investigator for NIH R01 funding and recently as co-principal investigator for the UCLA research site of the NIH sponsored Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) grant, a $37.5 million, five-year effort funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH).
http://vsuinstitute.com/
Dr. Veronikis: for more information you can email him at [email protected]. He does request the following information via fax (314-251-4492) or email: Index operative report and any subsequent surgical procedures as well as the operative implant log. This information allows him quickly to understand each individual lady’s symptoms and needs. You can expect a rather rapid response from Dr. V as he checks his emails throughout the day.You can learn more about Dr. Dionysios K. Veronikis’ practice location and view mesh removal pictures at www.drveronikis.com and patient ratings at his Healthgrades page here Healthgrades/Veronikis.
http://tvtno.org/doctors-that-care/dr-tom-margolis-surgeon-doing-what-is-right-through-adversity/
Approximately 15 years ago when device makers asked doctors to begin using transvaginal mesh devices, one doctor stood up against the dangerous devices. “No. I will not do this. This violates core basic surgical tenets,’” explained Surgeon Doctor Tom Margolis when asked if he uses or has used TransVaginal mesh. Dr Margolis has kept his stand against TVM, refusing to use mesh in the treatment of women suffering from stress urinary incontinence and pelvic organ prolapse. Dr. Margolis of the Bay Area Pelvic Surgeons has not only refused to use transvaginal mesh kits, but has spoken out against the faulty devices to the during FDA hearings on Transvaginal mesh and has been very out spoken in the media as well. (Read the transcript here)
A major issue with TransVaginal mesh is the placement of the mesh through the contaminated vagina. With this procedure there is no way to prevent bacteria from attaching to the mesh and entering into the body causing major infections, mesh erosion as well as becoming contaminated and breaking down in the body. Dr. Margolis is one of the few doctors that understands this basic concept and treats women with mesh complications safely.
https://www.google.ca/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CDwQFjAA&url=http%3A%2F%2Fwww.noinsurancesurgery.com%2Fhernia%2Fhernia-mesh-removal.htm&ei=Pf0YU-zaCtHroAS8Bg&usg=AFQjCNHZCYDneRl9CC3AXTcmzCEA_scptg&sig2=2U4YKbh5CwNy4kddpPkHhQ
Hernia Mesh Removal | No Insurance Surgery
by Kevin Peterse....Our experience with mesh removal has been that roughly 80% of patients are cured or significantly improved. These results are good enough to recommend the surgery to patients who have exhausted other treatments and who still have significant pain. We tell patients that if they can manage the pain by other means they should not have the mesh removed. ......20% of patient who have removal of mesh for pain do not have significant improvement of their of pain. Fortunately we have not seen anyone who's pain has worsened. We hypothesize that the patients who continue to have pain continue to produce scar tissue no matter what you do. Also, many patients with chronic severe pain from hernia mesh develop PTSD (post traumatic stress disorder) which can be difficult to recover from.......Another more concerning possible issue related to mesh is the possibility that it causes cancer. We have not seen any cases of cancer caused by mesh but we have heard anecdotal cases. It is a well know phenomenon that chronic chemical or mechanical irritation anywhere in the body can cause cancer. Mesh is a constant chemical and mechanical irritant to the body in some patients. The truth is that mesh is not bio-compatible.
A recent publication in a very well repected surgery medical journal says "The value of open inguinal herniorraphy without mesh is being lost. Mesh herniorraphy is being inappropriately used as the standard of care. The complication ofinguinodynia is occurring at inappropriately high rates. Ilioinguinal neurectomy is not a simple solution."
Am J Surg. 2012 Apr;203(4):550. Epub 2008 Sep 11. Inguinodynia and ilioinguinal neurectomy. Danto LA
https://www.uclahealth.org/provider/shlomo-raz-md
FDA classification of surgical mesh :
(surgical mesh is classified as class 2 by the FDA in the USA, curious as to why when it is a permanency deviced implant)
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/ObstetricsandGynecologyDevices/UCM270402.pdf
Special Controls apply only to Class II devices. Special Controls may include one or
more of the following:
• physician labeling
• patient labeling
• premarket studies, e.g., bench studies, animal studies, clinical studies to
demonstrate substantial equivalence
• performance standard(s)
• guidance document
• enhanced postmarket surveillance
• patient registry
Class III devices are subject to an independent assessment of safety and effectiveness
during premarket review. This includes the following premarket and postmarket
controls:
• Premarket submission of valid scientific evidence to determine reasonable
assurance of safety and effectiveness as described in 21 CFR 860.7 (b)(2)
• In depth premarket review of manufacturing information and pre-approval manufacturing inspection
• Post-approval studies to obtain long-term data (if needed)
• Annual reporting
• All postmarket device and labeling changes must be reported to FDA (significant
changes require approval by the FDA prior to implementation)
2.2 Premarket Review of Medical Devices
Many Class II and most Class I devices are exempt from premarket review. The FDA
reviews premarket notifications or 510(k) submissions for most Class II devices to
determine whether the device is “substantially equivalent” to a legally marketed Class II
device. In contrast to the determination the FDA makes in evaluating a premarket
approval (PMA) application for Class III devices, the 510(k) review is comparative.
510(k) submissions may contain clinical data; however, these data are used to
demonstrate substantial equivalence rather than to independently provide a reasonable
assurance of safety and effectiveness for the device. Only Class III devices subject to
PMA requirements allow for an independent assessment of safety and effectiveness
premarket.
Foreign Body Response:
http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDRH/CDRHFOIAElectronicReadingRoom/UCM246513.pdf
Device Description The GYNECARE TVT SECUR* device is a sterile, single patient use device, consisting of one piece of undyed or blue
(Phtalocyanine blue, Color index Number 74160) PROLENE* ADVERSE REACTIONS
* Transitory local irritation at the wound site and a transitory foreign body response may occur. This response could result in extrusion, erosion, fistula formation or inflammation. ( observation: there was no mention of the fact that there could be a chronic foreign body response)
* As with all foreign bodies, PROLENE mesh may potentiate an existing infection, The plastic sheaths initially covering the PROLENE mesh are designed to minimize the risk of contamination.
ACTIONS
Animal studies show that implantation of PROLENE mesh elicits a minimal inflammatory reaction in tissues, which is transient and is followed by the deposition of a thin fibrous layer of tissue, that can grow through the interstices of the mesh, thus incorporating the mesh into adjacent tissue. The material is not absorbed, nor is it subject to degradation or weakening by the action of tissue enzymes.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2327202/
The development of novel biomaterials, biomedical devices, or tissue-engineered constructs necessitates a thorough understanding of the biological responses to implanted materials. Once a biomaterial is introduced into the body, a sequence of events occurs in the surrounding tissue and ultimately ends in the formation of foreign body giant cells at the tissue/material interface. The consequences of the reaction to the material surface can be devastating.....Biomaterial adherent macrophages therefore can secrete proteins that modulate fibrosis and in turn the fibrous capsule that develops around a material following implantation. This fibrous capsule can interfere with biomaterial function, depending on the intended use of the medical device, prosthesis, or biomaterial.......oxidation as a key process in the degradation and implicated ROIs such as superoxide anion and/or hydroxyl radicals, as potential participants in this oxidative process.[89]....With biocompatible materials, early resolution of the acute and chronic inflammatory responses occurs with the chronic inflammatory response composed of mononuclear cells usually lasting no longer than two weeks. The persistence of the acute and/or inflammatory responses beyond a three week period usually indicates an infection. (observation: no mention of what the problem is if chronic increasing inflammation is not infection caused prolonged inflammatory response , for example device rejection leading to device failure)
http://link.springer.com/chapter/10.1007/978-0-387-37880-0_10
The success of the entire operation depends on the kind and degree of tissue response to the surgical procedure and any interactions between tissues and implants. The local and systemic response of the tissues toward implants comprise an aspect of biocompatibility.
http://link.springer.com/article/10.1007%2Fs10029-011-0885-y/fulltext.html
,,,,,,,, The inflammatory responses to the more frequently used mesh products have been investigated on human explants by Klinge et al. [4], who confirm the view that mesh materials used for soft tissue reinforcement elicit a chronic inflammatory response that is persistent over time. Histological observations describe an implanted permanent mesh, typically characterized by a foreign body granuloma adjacent to the mesh fiber and a surrounding collagen capsule that shields the host from the foreign material. It is reasonable to assume that this chronic inflammatory process impairs normal wound healing and tissue regeneration [5] .....
This study, which to the best of our knowledge is the longest preclinical evaluation of surgical meshes conducted to date, verifies previous knowledge on the long-term tissue response to polypropylene. The control mesh elicited an acute inflammatory response that is persistent over time, and that turns into a chronic inflammation characterized by foreign-body granulomas surrounding the fibers and a layer of mature collagen, effectively screening the foreign material from the surrounding tissue. Following explantation at 24 and 36 months, the polypropylene mesh was macroscopically not well integrated and was still stiff, and was shown histologically to be encapsulated by well-organized and mature collagen. This corresponds well to previous knowledge of how a host organism protects itself from a foreign object [23].
https://www.google.ca/url?sa=t&rct=j&q=&esrc=s&source=web&cd=5&ved=0CE4QFjAE&url=http%3A%2F%2Fwww.researchgate.net%2Fpublication%2F14066557_Characterization_of_cellular_response_to_silicone_implants_in_rats_implications_for_foreign-body_carcinogenesis%2Ffile%2F5046351a4aa629a68a.pdf&ei=1hRLU9PCNJKCyAGDzYGQCg&usg=AFQjCNGVvNgPqiwtI2T_x-cFfjMlnDQeZg&sig2=jKa3F5bfV-YgYoNy0shKTgCharacterization of cellular response to silicone implants in rats: implications for foreign-body carcinogenesis :
S. Jill James, Marta Pogribna, Barbara J. Miller, Brad Bolon*
and Levan Muskhelishvili FDA National Center for Toxicological Research, Jefferson, AR 72079, USA; *Pathology Associates international (an SAlC Company), Jefferson, AR 72079, USA
Foreign-body (FB) carcinogenesis is a classic model of multistage tumour development in rodents.
Previous studies have demonstrated that the physical characteristics of the implant, and not the chemical
composition, are the critical determinants of tumour development. The recent controversy over silicone
breast implants has raised questions regarding the potential carcinogenicity of lifetime tissue exposure to
silicone products, The present study was designed to determine whether the inflammatory and fibrotic
reactions associated with silicone implants are due to a non-specific foreign-body reaction or whether these responses reflect the unique chemical composition of silicone. ................. Brand et ~1.~ concluded that the chemical nature of the implants was not a critical factor in FB carcinogenesis, but that tumour formation was directly
667 Biomaterials 1997, Vol. 18 No. 9 668 Cellular response to silicone implants in rats: S.J. James et al. related to cellular events during the FB reaction and formation of the fibrotic capsule surrounding the implant. Subsequent studies have extended these observations and demonstrated tha subcutaneously implanted materials of any chemical composition can cause tumours in several animal species provided they possess a smooth impermeable surface7X8. In powdered, perforated or porous form, these materials lose their tumorigenicity5, c ............The expression of iNOS has been functionally linked to oxygen free radical production32 and may partially explain the presence of DNA strand breaks in the present study. Activated leucocytes have been shown to induce persistent DNA strand breaks33 and malignant transformation in neighbouring cells34V35. In other studies, nitric oxide exposure in vitro resulted in DNA strand breaks and mutagenesis3”. Unrepaired DNA strand breaks are a significant DNA lesion that can predispose to malignant transformation37. Pertinent to the present study, a significant increase in cell proliferation (PCNA+ growth fraction) and apoptotic cell death was associated with a significant increase in DNA strand breaks in the tissue adjacent to the carcinogenic implants in Groups 1 and 2. H........... ( this appears to infer that FBR is linked to carcinogenisis)
http://www.sciencedaily.com/releases/2014/02/140212132805.htmSurgical implants: Implant stiffness is a major cause of foreign body reaction Date:February 12, 2014 Source:University of Cambridge Summary: Surgical implants are widely used in modern medicine but their effectiveness is often compromised by how our bodies react to them. Now, scientists have discovered that implant stiffness is a major cause of this so-called foreign body reaction.
http://techtransfer.universityofcalifornia.edu/NCD/23713.html
........In contrast, host cells express surface proteins that are specifically recognized by immune cells, leading to inhibition of inappropriate inflammatory immune activation and prevention of spurious activation on self tissue. These immunomodulatory molecules are required for maintaining homeostasis and preventing immune hyperactivity, and defects in their expression have been shown to lead to chronic inflammation, autoimmunity, or allergy.
fragmentation:
http://meshmedicaldevicenewsdesk.com/latest-in-the-litigation-concerning-mesh-and-medical-devices/batiste-v-ethicon-trial-an-unexpected-emotional-rollercoaster-in-texas/#comment-169133
........And he was the first expert witnesses to use the word “plastic” repeatedly, not polypropylene (as plastic is often referred to during trial). This reporter believes “plastic” is a more accessible word for jurors to understand the reality of what the mesh actually is.
And Margolis added, “There is no way to remove 100 percent of the mesh,. . . ever.” He said it is a permanent implant that no doctor can currently remove 100% of, including the free floating particulate matter, as the mesh breaks down or when partial surgeries are performed in an attempt to explant as much mesh as possible. “Your immune system will attack [the plastic] and attack it, and attack it for the rest of the your life, but our bodies did not evolve to be able to reject mesh through the mechanism of our autoimmune systems.” In other words, the body’s attempt to attack the foreign invader will continue as long as the mesh is present in any amount, and it will do so to no avail, try as it might.
free radicals : (degradation products of the oxidization of PP in the human body)
http://bmb.oxfordjournals.org/content/43/2/371.shortFree radicals in biological systems—a review orientated to inflammatory processes, D R Blake, R E Allen and J Lunec
+Author Affiliations Rheumatism Research Wing, The Medical School, University of Birmingham Birmingham
Abstract :Free radicals are chemical species with one or more unpaired electrons in their outer orbital. Their production is essential to normal metabolism but they are theoretically destructive unless tightly controlled. We review the chemistry of free radical production and the intra/extracellular defence systems that limit their toxicity. Particular reference is made to biochemical processes which we believe are relevant to maintaining an inflammatory reaction. As a clinical illustration we describe mechanisms pertinent to the perpetuation of the chronic inflammation of rheumatoid synovitis.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249911/
A free radical can be defined as any molecular species capable of independent existence that contains an unpaired electron in an atomic orbital. The presence of an unpaired electron results in certain common properties that are shared by most radicals. Many radicals are unstable and highly reactive. They can either donate an electron to or accept an electron from other molecules, therefore behaving as oxidants or reductants.[5] The most important oxygen-containing free radicals in many disease states are hydroxyl radical, superoxide anion radical, hydrogen peroxide, oxygen singlet, hypochlorite, nitric oxide radical, and peroxynitrite radical. These are highly reactive species, capable in the nucleus, and in the membranes of cells of damaging biologically relevant molecules such as DNA, proteins, carbohydrates, and lipids.[6] Free radicals attack important macromolecules leading to cell damage and homeostatic disruption. Targets of free radicals include all kinds of molecules in the body. Among them, lipids, nucleic acids, and proteins are the major targets.
Production of free radicals in the human bodyFree radicals and other ROS are derived either from normal essential metabolic processes in the human body or from external sources such as exposure to X-rays, ozone, cigarette smoking, air pollutants, and industrial chemicals.[3] Free radical formation occurs continuously in the cells as a consequence of both enzymatic and nonenzymatic reactions. Enzymatic reactions, which serve as source of free radicals, include those involved in the respiratory chain, in phagocytosis, in prostaglandin synthesis, and in the cytochrome P-450 system.[7] Free radicals can also be formed in nonenzymatic reactions of oxygen with organic compounds as well as those initiated by ionizing reactions.
Some internally generated sources of free radicals are[8]
- Mitochondria ,Xanthine oxidase , Peroxisomes
- Inflammation
- Phagocytosis
hernia mesh:
http://pubmedcentralcanada.ca/pmcc/articles/PMC3470559/
Hernia repair is the most common surgical procedure. About one million procedures are carried out worldwide each year [1]. In the last two decades, procedures using artificial, alloplastic meshes gained importance and demonstrated superiority over conventional procedures such as direct suture and Mayo repair in terms of recurrence [2], [3]. (note :in terms of recurrence is not addressing quality of life after mesh implantation, as in pain free and no symptoms of adverse systemic response)
- DYNAMESH-IPOM®. This mesh is distributed by P. J. Dahlhausen & Co. GmbH (Cologne, Germany). It is manufactured by FEG Textiltechnik (Aix-la-Chapelle, Germany). It is a 2-component knitted fabric made from PVDF (polyvinylidene fluoride) monofilament on the visceral side of the mesh and polypropylene monofilament on the parietal side. It is used for reinforcing connective tissue structures. The mechanical properties claimed by the manufacturer are determined with a punch test. A “stability” of 38 N/cm and an “elasticity” of 34% are claimed [19].
- PARIETENE®. This mesh is manufactured by Sofradim (Trévoux, France) and distributed by Tyco Healthcare (Neustadt (Donau), Germany). It is made from a monofilament polypropylene mesh with hexagonal open stitching and is supposed to have a “multidirectional elasticity”. It is designed for preperitoneal and premuscular hernia repair.
- PROLENE MESH®. This mesh is manufactured by Johnson-Johnson Inc. (Langhorne, PA, USA) and distributed by Johnson-Johnson Inc. (Neuss, Germany). It is a construction of knitted non-absorbable filaments of polypropylene, identical in composition to that used in PROLENE® suture. The knitting-process interlinks each fibre junction and provides for extensibility in both directions. This construction is supposed to permit the mesh to be cut into any desired shape or size without unravelling. The bi-directional extensible property allows adaptation to various stresses encountered in the body. According to manufacturer's data the mesh has a burst strength of approximately 14 kg/cm2.
- SURGIPRO Pro®. This mesh is manufactured by United States Surgical (Norwalk, CT, USA) and distributed by Tyco Healthcare (Neustadt (Donau), Germany). It is knitted from undyed monofilament polypropylene and provides bi-directional elasticity. It is used for hernia repair and the reinforcement of other fascial defects.
- ULTRAPRO MESH®. This mesh is manufactured by Johnson-Johnson Inc. (Langhorne, PA, USA) and distributed by Johnson-Johnson Inc. (Neuss, Germany). It is used for repair of hernias or other abdominal fascial defects. This mesh is manufactured from approximately equal parts of absorbable poliglecaprone-25 monofilament fibre and non-absorbable polypropylene monofilament fibre. The polymer of the dyed and undyed polypropylene fibre (phtalocyanine blue, colour index No.: 74160) is identical to the material used for dyed and undyed suture material. Poliglecaporne-25 consists of a co-polymer containing glycolide and α-caprolactone. This polymer is also used for MONOCRYL® suture material. After absorption of the poliglaceprone-25 component only the polypropylene mesh remains. The structure and size of this remaining mesh is supposed to bear the physiological stresses to which the abdominal wall is subject.
- VICRYL®. This mesh (style 9; VM3020) is manufactured by Johnson-Johnson Inc. (Langhorne, PA, USA) and distributed by Ethicon (Norderstedt, Germany). It is made completely from resorbable undyed polyglactin. According to the manufacturer, it is indicated for temporary wound or organ support.
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0080647
Behaviour of a New Composite Mesh for the Repair of Full-Thickness Abdominal Wall Defects in a Rabbit Model Gemma Pascual, Sandra Sotomayor, Marta Rodríguez, Yves Bayon, Juan M. Bellón.....
While conventional biomaterials such as polypropylene or polyester achieve good abdominal repair both in terms of tissue and biomechanical behaviour, when placed in contact with the visceral peritoneum these materials can lead to complications such as tissue adhesions or abdominal obstruction [11], mesh migration to hollow organs [12], or to more serious complications such as intestinal fistula [13,14]. To avoid these adverse events, composites consist of two biomaterials one of which acts as a non-absorbable barrier [15]. Given its proven good peritoneal behaviour, one of the most used barrier components of composites is polytetrafluoroethylene (PTFE) [16,17].
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0021228
The biomechanical properties of biologic mesh significantly decline after colonization with MRSA. Surgeons selecting a repair material should be aware of its biomechanical fate relative to other biologic materials when placed in a contaminated environment.
http://www.ncbi.nlm.nih.gov/pubmed/21909779
Biomechanical compatibility of surgical mesh and fascia being reinforced: dependence of experimental hernia defect repair results on anisotropic surgical mesh positioning.Anurov MV1, Titkova SM, Oettinger AP.
Author information
AbstractPURPOSE:We aimed to compare the effectiveness of experimental middle hernia defect repair in regard to the transverse and longitudinal positioning of anisotropic lightweight surgical mesh.
METHODS:The mechanical properties of fascial layers and surgical mesh DynaMesh(®)-PP Light were determined in two perpendicular directions under uniaxial tension. In 12 male Wistar rats, middle hernia defect was repaired by the sublay technique. In six animals, the mesh was positioned across (DLH group) and in the other six along (DLV group) the midline. At 6 months after implantation, mesh deformation, structural rearrangement, and repaired abdominal wall biomechanics were evaluated. Histological sections were stained with van Giesen and Mallory's trichrome.
RESULTS:The anisotropic mechanical properties of the mesh and fascial layers coincided in the DLH group, but did not correspond to each other in the DLV group. In the DLV group, meshes were stretched in width by 11.4% and reduced in length by 12.7%. In all animals, the lower edge of the mesh was shifted to a defect area with margin hernia formation in two rats. Constant shear stress caused disproportional connective tissue formation. Repaired abdominal wall lost its natural elasticity. In the DLH group, the mesh deformation was minimal. Formed connective tissue was tightly associated with the anterior layer and did not differ from it in composition. The mechanical properties of repaired abdominal wall were close to those of the anterior layer.
CONCLUSIONS:In prosthetic hernia repair, the mechanical properties of surgical mesh should correspond with those of the fascia being repaired. A mismatch of mechanical properties may result in implant deformation, abdominal wall biomechanics impairment, and recurrent herniation at the edges of the meshes.
PMID: 21909779 [PubMed - indexed for MEDLINE] ( begs the questioning of mesh contraction when saying mesh is biomehanical compatible ) ( also note in studies quality of life was not included in the ratings of success )
http://meshmedicaldevicenewsdesk.com/wp-content/uploads/2014/03/atrium-proloop-mesh.jpg
hernia mesh lawsuit filed ........
In fact, a debilitating consequence of hernia repair with mesh is inguinodynia, or chronic groin pain. This condition results from the deformation of mesh following implantation, the persistent foreign body reaction to mesh, and nerve entrapment in the mesh. The medical literature reports an extraordinarily high rate of chronic groin pain after hernia repair with mesh – in some reports approaching 50%, and even higher in others. Moreover, as the mesh degrades in the human body, small flakes of polypropylene can lead to infection and irritation, and severe pain as the body tries to rid itself of the foreign material....................
history of TVT mesh articles:
http://naturalhealthnews.blogspot.ca/p/womens-health-transvaginal-mesh.html
Natural Health News: FDA slow to take action on vaginal mesh Oct 12, 2011
FDA slow to take action on vaginal mesh. In September2011 the FDA convened a conference on the use of TV mesh and the consideration for changing its device classification to a more stringent one. Now the FDA is calling ... Natural Health News: Transvaginal Mesh and Women's Health Sep 29, 2011
Lawsuits claiming negligence against mesh-makers have also implicated the FDA's review system for continuing to clear new mesh products under the 510(k) system, despite the predicate device being pulled from U.S. ...The Ten Year WindowI have spent many years in the health care industry. The outcome of the observations I have made tells me that most often it takes about 10 years for facts to catch up with drug, treatments, and device approvals. Approvals in this arena come from the Food and Drug Administration (FDA). Commonly, because of the faster fast track system instituted now for a couple of decades, money buys the ticket to the train. When first instituted Fast Track cost a manufacturer about $330,000; now it is at least double.This doesn’t end up doing too much for safety because, if you follow the news, you too frequently hear about a drug recall, an ineffective treatment, or medical device failures along with product liability law suits.
Implant Syndrome:
http://www.ehcd.com/pdf/Implant_Syndrome_070711.pdf
A classic model for the induction of chemical sensitivity has now been devised. The surgical use of artificial implants can induce both autoimmune disease and chemical sensitivity.
The following are two case reports of the severe complications that one can develop after mesh implants.Case Study #1. A 45-year old white female was well until she had a large abdominal hernia repaired with a synthetic mash graft. When she awoke from surgery, she had severe asthma (which she had never had before) that was intractable to all forms of treatment. She became cortisone dependent, requiring 80 to 100 mg of prednisone per day in order to survive, even though the asthma continued to incapacitate her. She became very odor sensitive, developing all the classic signs and symptoms of chemical sensitivity. She also
developed autoimmune disease with Raynaud’s phenomenon, spontaneous bruising, peripheral and periorbital edema, and cold sensitivity. This patient underwent challenge testing and was found to be sensitive to toxic chemicals and electromagnetic fields. Removal of the abdominal mesh resulted in immediate cessation of the asthma, which had been present since its insertion 5 years earlier. The chemical sensitivity diminished rapidly, but the electrical sensitivity persisted. The patient lost her need for prednisone and lost her sensitivity to chemicals. She improved markedly with pollutant avoidance techniques and nutritional supplementation. Autonomic disease with arthralgia, fibromyalgia, chronic fatigue, and organic brain syndrome has been seen upon examination in the majority of patients with breast or any implants. These symptoms subside with removal of the implants and their capsules, although injection therapy for secondary sensitivities to biological inhalants, and synthetic implant antigens, foods, chemicals, as well as heat depuration/physical therapy is necessary in some patients. (For details of the implant-induced disease, see Rea, Chemical Sensitivity, Volume III, Chapter 19,(1) and Chemical Sensitivity, Volume IV, Chapter 41.(2))
http://www.ehcd.com/implant-syndrome/
Mesh is sometimes chosen to repair hernia or muscle and tissue tears.
These implanted or substituted materials fill important needs. However, sometimes the human body objects to a particular material. Symptoms such as joint pain, fatigue, nausea, headache, immune suppression, increased sensitivities to foods, inhalants and chemicals, irritable bowel syndrome, vasculitis, respiratory dysfunction, and muscle and joint pain can occur. Frequently it is difficult to connect cause and symptom.
The Environmental Health Center-Dallas is a leader in the field of diagnosing and treating those who suffer with symptoms which seemed to occur after the implantation of metal, plastic, silicone, acrylic, methacrylate, or plastics in the body.
Immunologic Reaction to Polypropylene Mesh:
http://clinicaltrials.gov/ct2/show/NCT01090284
The Immunologic Reaction to Polypropylene Mesh in Inguinal HernioplastyThe recruitment status of this study is unknown because the information has not been verified recently.Verified February 2010 by University Hospital, Catania. Recruitment status was Recruiting
Sponsor:University Hospital, CataniaInformation provided by:University Hospital, CataniaClinicalTrials.gov Identifier:NCT01090284
First received: March 18, 2010 Last updated: March 22, 2010
Last verified: February 2010
History of Changes
PurposeThe notable development and diffusion of prosthetic surgery of the abdominal wall over the last few years has led to the introduction of light weight meshes. The efficacy of inguinal hernia repair with light weight prosthesis, as well as the better or worse biotolerability with respect to those of light weight, remains questionable in literature, where a clear answer still remains to be given. If there exists a connection between the quantity of material implanted, the immunological reaction to the mesh, the induced oxidative stress and the degree of cicatrization, and consequently the long-term result of the efficacy of the operation, remains to be demonstrated. There are few studies on the immunological reaction to polypropylene meshes, and none on the oxidative stress induced by the mesh. Moreover, only one study has been published that clearly correlates the immunological reaction to the amount of prosthetic material, but was carried out on only a few patients.
The aim of this research is to show if there is a relationship between the amount of prosthetic material used and immunological reactions as well as postoperative oxidative stress, and thus to evaluate, if present, the differences in the biological reaction and biotolerability between light-weight and heavy-weight meshes on a statistically significant number of patients.
infection:
http://www.health.harvard.edu/blog/infection-autoimmune-disease-linked-to-depression-201306176397 ........
Infection causes localized and body-wide inflammation. Inflammation generates substances called cytokines that have been shown to change how brain cells communicate. In autoimmune diseases, the body’s defense system attacks healthy tissues rather than threatening invaders. It’s possible that in some cases the wayward immune reaction could target brain cells and other nerve cells throughout the body.........
http://www.health.state.mn.us/divs/idepc/diseases/staph/basics.html
- S. aureus is most often spread to others by contaminated hands.
The skin and mucous membranes are usually an effective barrier against infection. However, if these barriers are breached (e.g., skin damage due to trauma or mucosal damage due to viral infection) S. aureus may gain access to underlying tissues or the bloodstream and cause infection. - Persons who are immunocompromised or who have invasive medical devices are particularly vulnerable to infection.
inflammation:
http://www.novomedics.ch/cms/daten/file/tutomesh_incisional.pdfEven after years polypropylene meshes show a moderate foreign-body reaction with activated macrophages and neutrophilic .....
biofilm-producing staphylococci could be demonstrated in up to 30% of the specimens ......One of the propylene meshes had a brittle and crumbly appearance. In 10 cases sharp edges had already formed, which started to perforate the peritoneum. All samples showed a
chronic, persistent inflammatory reaction regardless of whether an infection was present or not.......the risk for peritonitis or fistulation is unacceptably high.
https://www.inkling.com/read/robbins-basic-pathology-kumar-abbas-aster-9th/chapter-2/chronic-inflammation
- Immune-mediated inflammatory diseases (hypersensitivity diseases). Diseases that are caused by excessive and inappropriate activation of the immune system are increasingly recognized as being important health problems (Chapter 4). Under certain conditions, immune reactions develop against the affected person’s own tissues, leading to autoimmune diseases. In such diseases, autoantigens evoke a self-perpetuating immune reaction that results in tissue damage and persistent inflammation. Autoimmunity plays an important role in several common and debilitating chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Immune responses against common environmental substances are the cause ofallergic diseases, such as bronchial asthma. Immune-mediated diseases may show morphologic patterns of mixed acute and chronic inflammation because they are characterized by repeated bouts of inflammation. Since, in most cases, the eliciting antigens cannot be eliminated, these disorders tend to be chronic and intractable.
- Prolonged exposure to potentially toxic agents. Examples are nondegradable exogenous materials such as inhaled particulate silica, which can induce a chronic inflammatory response in the lungs (silicosis, Chapter 12), and endogenous agents such as cholesterol crystals, which may contribute to atherosclerosis (Chapter 9).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1475883/
higher inflammatory response compared to BH, likely due to polypropylene mesh [9,10].
http://www.scientificamerican.com/article/chronic-inflammation-cancer/
The possibility of a link with a third major killer—cancer—has received intensive scrutiny in this decade. “The connection between inflammation and cancer has moved to center stage in the research arena,” notes Robert A. Weinberg of the Massachusetts Institute of Technology’s Whitehead Institute for Biomedical Research, who has highlighted the changing emphasis in a revision of his leading textbook, The Biology of Cancer (Garland Science, 2006).
This transformation recognizes that the immune inflammatory state serves as a key mediator of the middle stages of tumor development. Cancer begins with a series of genetic changes that prompt a group of cells to overreplicate and then invade surrounding tissue, the point at which true malignancy begins. Eventually some tumor cells may break off and establish new growths (metastases) at distant sites. That much has been understood for a long time. But cancer biologists and immunologists have begun to realize that the progression from diseased tissue to full-blown invasive cancer often requires cells that normally participate in healing cuts and scrapes to be diverted to the environs of the premalignant tissue, where they are hijacked to become co-conspirators that aid and abet carcinogenesis. As some researchers have described the malignant state: genetic damage is the match that lights the fire, and inflammation is the fuel that feeds it.
http://www.answers.com/topic/inflammation:In acute inflammation, if the injurious agent persists then chronic inflammation will ensue. This process, marked by inflammation lasting many days, months or even years, may lead to the formation of a chronic wound. Chronic inflammation is characterised by the dominating presence of macrophages in the injured tissue. These cells are powerful defensive agents of the body, but the toxins they release (including reactive oxygen species) are injurious to the organism's own tissues as well as invading agents. Consequently, chronic inflammation is almost always accompanied by tissue destruction.
http://link.springer.com/article/10.1007%2Fs10029-011-0885-y/fulltext.html
,,,,,,,, The inflammatory responses to the more frequently used mesh products have been investigated on human explants by Klinge et al. [4], who confirm the view that mesh materials used for soft tissue reinforcement elicit a chronic inflammatory response that is persistent over time. Histological observations describe an implanted permanent mesh, typically characterized by a foreign body granuloma adjacent to the mesh fiber and a surrounding collagen capsule that shields the host from the foreign material. It is reasonable to assume that this chronic inflammatory process impairs normal wound healing and tissue regeneration [5] .....
This study, which to the best of our knowledge is the longest preclinical evaluation of surgical meshes conducted to date, verifies previous knowledge on the long-term tissue response to polypropylene. The control mesh elicited an acute inflammatory response that is persistent over time, and that turns into a chronic inflammation characterized by foreign-body granulomas surrounding the fibers and a layer of mature collagen, effectively screening the foreign material from the surrounding tissue. Following explantation at 24 and 36 months, the polypropylene mesh was macroscopically not well integrated and was still stiff, and was shown histologically to be encapsulated by well-organized and mature collagen. This corresponds well to previous knowledge of how a host organism protects itself from a foreign object [23].
infections:
http://onlinelibrary.wiley.com/doi/10.1111/j.1469-0691.2004.01014.x/full
Mesh-related infections after hernia repair surgery
Use of International Standard ISO-2 10993, "Biological Evaluation of Medical Devices Part 1: Evaluation and Testing" :
http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM348890.pdf
1. Introduction
FDA has developed this guidance document to assist industry in preparing Premarket
Applications (PMAs), Humanitarian Device Exemptions (HDEs), Investigational Device
Applications (IDEs), Premarket Notifications (510(k)s), and de novo requests for medical
devices that come into direct or indirect contact with the human body in order to determine the
potential toxicity resulting from contact of the component materials of the device with the body.
The purpose of this guidance is to provide further clarification and updated information on the
use of International Standard ISO-10993, "Biological Evaluation of Medical Devices Part 1:
Evaluation and Testing." . When final, this guidance will therefore replace ODE General
Program Memorandum #G95-1 (1995), entitled Use of International Standard ISO-10993,
"Biological Evaluation of Medical Devices Part 1: Evaluation and Testing.” This guidance
document also incorporates several new considerations, including assessment of known or
potentially toxic chemicals (e.g., color additives), and sample preparation for submicron or
nanotechnology components, in situ polymerizing and bioabsorbable materials, which were not
previously discussed in #G95-1.
leachates:
http://informahealthcare.com/doi/abs/10.1080/08916930701574331
Enhanced recognition of reactive oxygen species damaged human serum albumin by circulating systemic lupus erythematosus autoantibodies: 2007, Vol. 40, No. 7 , Pages 512-520 (doi:10.1080/0891693070157433
Zafar Rasheed, , Rizwan Ahmad, Naila Rasheed and Rashid AliDepartment of Biochemistry, Faculty of Medicine, AMU, Aligarh, 202002, India Department of Biochemistry, SBSPGI, Balawala, Dehradun, 248161, IndiaDivision of Pharmacology, Central Drug Research Institute, P.B. No. 173, Lucknow, IndiaDepartment of Biochemistry, Faculty of Medicine, JN Medical College, AMU, Aligarh, 202002, India, 91 9219345899, 91 135 2686231 [email protected]
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with autoantibodies as a near universal feature of the disease. Earlier investigations from our laboratory revealed increased oxidative damage in SLE patients. Therefore, we hypothesized that oxidative by-products, such as hydroxyl radical (√OH), could lead to neoantigens like √OH damaged human serum albumin (HSA), which could in turn initiate autoimmunity in SLE. In the present study, the binding characteristics of SLE autoantibodies with native and √OH damaged HSA were assessed. SLE patients (n = 74) were examined by direct binding ELISA and the results were compared with healthy age- and sex-matched controls (n = 44). High degree of specific binding by 52.7% of patients sera towards √OH damaged HSA, in comparison to its native analogue (p < 0.05) was observed. Normal human sera showed negligible binding with either antigen. Competitive ELISA and gel retardation assays reiterate the direct binding results. The increase in total serum protein carbonyl levels in the SLE patients was largely due to an increase in oxidized albumin. HSA of SLE patients (SLE-HSA) and normal subjects (normal-HSA) were purified. Spectroscopic analysis confirmed that the SLE-HSA samples contained higher levels of carbonyls than normal-HSA (p < 0.01). SLE-HSA was conformationally altered, with more exposure of its hydrophobic regions. Collectively, the oxidation of plasma proteins, especially HSA, might enhance oxidative stress in SLE patients.
KeywordsSystemic lupus erythematosus, autoimmunity, reactive oxygen species, human serum albumin
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112322/
Heat exposed PP releases biologically active degradation products affecting normal metabolic events [13
http://www.epa.gov/oppt/existingchemicals/pubs/actionplans/RIN2070-ZA09_NP-NPEs%20Action%20Plan_Final_2010-08-09.pdf
Release of NP during production of plastic Release of NPEs from emulsion polymerization processes (raises question of nonylphenol release during degradation of polypropylene/polymeric constructed meshes ?)
http://www.biotechniques.com/BiotechniquesJournal/2010/April/Interference-with-spectrophotometric-analysis-of-nucleic-acids-and-proteins-by-leaching-of-chemicals-from-plastic-tubes/biotechniques-227475.html?pageNum=4
leachates are composed of multiple additives and their breakdown products. In widely available polymers such as polypropylene, the processing, heating, and oxidation histories of different preparations will vary, as will the effects of aging.
http://www.eppendorf.com/int/img/consumables/Holt_GLJ09-1009.pdf
The use of dyes to create yellow and blue tips, or a range of possible colors of microfuge tubes, requires the presence of surfactants to solubilize the dye compounds. Markedly reduced activity of mitochondrial respiration in patient biopsy samples screened at a metabolic diseases clinic was attributed to inhibition of complex I by nonylphenol ethoxylate (NP-10), a surfactant used to solubilize the blue dye present in pipette tips purchased by the clinic [5]. Most laboratory disposables are manufactured from polypropylene, polyethylene ......
.....quaternary ammonium biocide, diHEMDA, that had leached........
http://www.pqri.org/workshops/leach_ext/imagespdfs/posters/Polymer_Additives_PQRI_Poster.pdf
INTRODUCTION TO POLYMER ADDITIVES AND STABILIZATION
1Pt6YgMi76SDG3ybgMA&inline=1&ext=1394145750&hash=ASuK1dIqSOFv9KF2
degradation products of polypropylene :
Alcyl radical ( R ) (carbon centered free radical)
Peroxy radical (R-OO ) (oxygen centered radical )
Alkoxy radical (R-O )
Hydroperoxide (R-OOH Æ R-O + OH)
http://cdn.intechopen.com/pdfs/37233/InTech-Thermal_oxidation_of_polypropylene_and_modified_polypropylene_structure_effects.pdf
The thermal oxidation of polyolefynes has been extensively investigated in various works. The investigation of the kinetics and mechanism of oxidation of solid polymers have shown convincingly that this process is a radical - chain with degenerate branching of kinetic
chains. In the thermal degradation, thermooxidation and thermal oxidative degradation of polymers play a major role alkyd (R*), alkoxide (RO*) and peroxide (RO2*) macroradicals and low molecular weight radicals (r*). The high reactivity of the past towards macromolecules strongly influences on aging processes. The chain reaction of the oxidation of a polymer includes alternate steps of the chain propagation proceeding either inside the same macromolecule or between two molecules. The investigation of kinetics of oxidation of the polymers, containing aliphatic groups ( C-H, -CH2- or –CH3), showed that this process was described by scheme, corresponding to the mechanism of chain oxidation of liquid phase (Denisov E.T. and all., 1975).
http://www.geotextile.com/downloads/Propex%20EB-405%20Durability%20of%20Polypropylene.pdf
Polypropylene oxidation is the reaction of free radicals within the polymer with oxygen, resulting in breakdown and/or degradation of the molecular chains and embrittlement of the polymer.
mesh excision:
http://www.ncbi.nlm.nih.gov/pubmed/24165449
Long-term symptom improvement and overall satisfaction after prolapse and incontinence graft removal.Rogo-Gupta L1, Huynh L, Hartshorn TG, Rodríguez LV, Raz S.
Author information
AbstractOBJECTIVES:We report long-term symptom improvements and overall satisfaction in patients after removal of grafts used in pelvic reconstruction in a tertiary referral center.
METHODS:We analyzed patients who underwent graft removal for treatment of related complications and who were followed for at least 2 years. Symptoms were determined by patient self-assessment questionnaires.
RESULTS:Seventy-nine patients underwent partial or complete graft removal from 2005 to 2011 and met inclusion criteria. The mean follow-up time was 4.0 years (median, 3.4 years; range, 2.0-7.6 years). Forty-seven percent (37 patients) had implants for both prolapse and incontinence, 40% (32 patients) had incontinence implants only, and 13% (10 patients) had prolapse implants only. Thirty percent of those with both implants presented with multiple symptoms compared to 50% of those with prolapse implants and 44% of those with incontinence implants only. At follow-up, 75% (56 patients) reported that their symptoms were better and 15% (11 patients) reported that their symptoms were worse. Of patients who underwent graft removal for pain alone, 74% (17 patients) improved whereas17% (4 patients) were worse. When asked about spending the rest of their lives with their current symptoms, 49% (38 patients) reported positively whereas 44% (34 patients) reported negatively. Forty-one patients underwent one or more additional treatments.
CONCLUSIONS:Graft-related complications are often treated with surgical excision. In a cohort of 79 patients in whom implants were removed an average of 4 years earlier, 75% still report symptom improvement and 49% report good quality of life. However, many patients still feel dissatisfied and sought additional treatment during long-term follow-up. These data can be used to counsel patients considering removal of pelvic reconstruction grafts.
PMID: 24165449 [PubMed - indexed for MEDLINE]
Mesh Related SIN Syndrome:
https://www.google.ca/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CB8QFjAA&url=http%3A%2F%2Fwww.scirp.org%2Fjournal%2FPaperDownload.aspx%3FpaperID%3D47982&ei=QTcmVLDxB4KLoQSZ44CIDw&usg=AFQjCNH0yXRHpJH7C2_sFj4HitBmGnhQ3A&sig2=0BuhNCbwCilpKr0DcSqmeA
Mesh-Related SIN Syndrome. A Surreptitious Irreversible Neuralgia and Its Morphologic Background in the Etiology of Post-Herniorrhaphy Pain Robert Bendavid1*#, Wendy Lou2, Andreas Koch3, Vladimir Iakovlev4*#
Shouldice Hospital, Thornhill, Canada
Department of Biostatistics, Dalla Lan School of Public Health, University of Toronto, Toronto, Canada 3
Day Surgery and Hernia Center, Cottbus, Germany 4
Department of Laboratory Medicine and Pathobiology, Keenan Research Centre of the Li Ka Shing Knowledge
Institute; Division of Pathology, St. Michael’s Hospital, University of Toronto, Toronto, Canada
Email: *[email protected], *
[email protected]
Surreptitious Irreversible Neuralgia (SIN). It is surreptitious because it is of
slow onset, unsuspected and enigmatic to clinicians; irreversible because the pain is progressive,
unrelenting and unresponsive to treatment. Removal of the mesh does not guarantee pain relief. .......
Conclusion: The
presence of mesh does not significantly affect nerve density, while the nerves and their terminal
ends are in a vulnerable position about the mesh and within its pores. These pores need to be viewed as “mini-compartments” of biological tissue where the vasculature, nerves and their terminal ends are in a vulnerable position about the mesh and in its pores. These pores need to be viewed as “mini-compartments” of biological tissue where the vasculature,nerves and their receptors are exposed to potential mechanical and chemical factors: scarring, entrapment, compression, tugging deformation contraction, hypoxia/acidosis, inflammation and edema
need for more studies /clinical trials:
http://clinicaltrials.gov/ct2/show/NCT01090284
The Immunologic Reaction to Polypropylene Mesh in Inguinal HernioplastyThe recruitment status of this study is unknown because the information has not been verified recently.Verified February 2010 by University Hospital, Catania. Recruitment status was Recruiting
Sponsor:University Hospital, CataniaInformation provided by:University Hospital, CataniaClinicalTrials.gov Identifier:NCT01090284
First received: March 18, 2010 Last updated: March 22, 2010
.......... The efficacy of inguinal hernia repair with light weight prosthesis, as well as the better or worse biotolerability with respect to those of light weight, remains questionable in literature, where a clear answer still remains to be given. If there exists a connection between the quantity of material implanted, the immunological reaction to the mesh, the induced oxidative stress and the degree of cicatrization, and consequently the long-term result of the efficacy of the operation, remains to be demonstrated. There are few studies on the immunological reaction to polypropylene meshes, and none on the oxidative stress induced by the mesh. Moreover, only one study has been published that clearly correlates the immunological reaction to the amount of prosthetic material, but was carried out on only a few patients.
The aim of this research is to show if there is a relationship between the amount of prosthetic material used and immunological reactions as well as postoperative oxidative stress, and thus to evaluate, if present, the differences in the biological reaction and biotolerability between light-weight and heavy-weight meshes on a statistically significant number of patients.
http://www.ncbi.nlm.nih.gov/pubmed/23090529
Trends in surgical mesh use for pelvic organ prolapse from 2000 to 2010.Rogo-Gupta L1, Rodriguez LV, Litwin MS, Herzog TJ, Neugut AI, Lu YS, Raz S, Hershman DL, Wright JD. Author information
Abstract: OBJECTIVE:To describe trends in and predictors of surgical mesh use for pelvic organ prolapse (POP) repair and to estimate the influence of safety advisories on mesh use.
METHODS:Analysis of women aged 18 years and older recorded in a health care quality and resource utilization database who underwent POP repair from 2000 to 2010, identified by International Classification of Diseases, 9th Revision, Clinical Modification procedure codes, and stratified by mesh use. Odds ratios were calculated with adjustments for patient, physician, and hospital-level characteristics.
RESULTS:Among 273,275 women in the cohort, 64,968 (23.8%) underwent a mesh-augmented repair. Concurrent incontinence surgery was a strong predictor of mesh use (odds ratio [OR] 9.95; 95% confidence interval [CI] 9.70-10.21). Mesh use increased from 7.9% in 2000 to a peak of 32.1% in 2006, and declined slightly to 27.5% in 2010. Among women without incontinence, mesh use increased from 3.3% in 2000 to 13.5% in 2006, and remained stable at 12.8% in 2010. Intermediate-volume (OR 1.53; 95% CI 1.44-1.62) and high-volume (OR 2.74; 95% CI 2.58-2.92) surgeons were more likely to use mesh than low-volume surgeons. Compared with women who underwent operation by gynecologists, those treated by urologists were more than three times more likely to undergo mesh-augmented prolapse repair (OR 3.36; 95% CI 3.09-3.66). Black women were 27% less likely to undergo mesh repair (OR 0.73; 95% CI 0.66-0.82).
CONCLUSIONS:Mesh-augmented prolapse repairs increased substantially over the past decade, and this increase was most pronounced in the years before the publication of safety advisories. Physician specialty and surgical volume are important factors underlying mesh use. Additional measures must ensure evidence-based use of mesh for pelvic reconstruction.
LEVEL OF EVIDENCE:II.
http://contemporaryobgyn.modernmedicine.com/contemporary-obgyn/news/vaginal-mesh-complications-and-miscommunications?contextCategoryId=153“We recommend improved communication between surgeon and pathologist first and foremost through more complete documentation to aid the pathologist's examination and enable understanding of the pathophysiology of mesh complications,” the authors write in the July-August issue of Female Pelvic Medicine & Reconstructive Surgery. “This is particularly germane as this subject is ‘under the microscope,’ as it were, by health care providers, regulatory bodies, the legal system and patients.”
The researchers, of the Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology, University of Michigan Health System, Ann Arbor, studied the process by which specimens from vaginal mesh removal operations are submitted to pathology departments for evaluation. Their most striking finding was of limited surgical team documentation of mesh product type or material type on pathology requisition forms. While such requisition details might seem trivial, the authors note, these details help guide the pathologic exam. Explants containing metal or other nonbiological material generally cannot be submitted for standard tissue processing and sectioning. This is because metal and other foreign materials may not be sectioned and made into slides by standard means. “No history was provided to the pathologist in 24.5% and the mesh type or product name was indicated on only 7% of requisitions. In the absence of this information, 1 in 5 specimens were described as “metal” or “metallic,” reports that would clearly be confusing and potentially damaging in the current climate of escalating regulatory and medicolegal concerns,” said Tovia Smith, MD.
Grossly undetectable metal fibers may prevent sectioning. Even fine polypropylene mesh fibers may make tissue evaluation difficult due to splintering or lack of adhesion to slides. The group suggests that either gross or histopathologic examination is appropriate for mesh explants. They found that documentation of clinical history, mesh product, and material was frequently incomplete and associated with increased submission of tissue for histology and inaccurate gross impression of material type. They recommend improved documentation to aid pathologic examination and enable future study of the pathophysiology of mesh complications.
Smith TM, Smith SC, DeLancey JO, et al. Pathologic evaluation of explanted vaginal mesh: Interdisciplinary experience from a referral center. Female Pelvic Med Reconstr Surg. 2013;19(4):238-241.
See more at: http://contemporaryobgyn.modernmedicine.com/contemporary-obgyn/news/vaginal-mesh-complications-and-miscommunications?contextCategoryId=153#sthash.SR0u0FA0.dpuf
http://www.kristin-jenkins.com/pages/medical/breakoutpages/KJ_uro_corcos.html
Dr. Jacques Corcos warned delegates to Urogynecology Quebec 2007 that many of the sub-urethral sling products currently on the market have not undergone adequate clinical testing. Dr. Corcos is director of the urology department at Jewish General Hospital, Montreal, and professor of urology at McGill University........ Since products for surgical interventions can be marketed directly to surgeons without the same kind of rigorous testing required for new medications, a lot of the evidence supporting their use is anecdotal.......Rigorous prospective safety and efficacy analysis of the Sparc suprapubic sling is also lacking, said Dr. Corcos. Several small retrospective studies, in Australia and elsewhere, have indicated that Sparc performs equally well as Monarc for the treatment of SUI. However, a recent trial (Lord HE et al, BJU Int2006; 98(2):367-376) comparing TVT and Sparc disputes this claim, demonstrating statistically significant operative difficulties as well as post-operative complications, including mesh erosion and a lower overall cure rate. “This trial highlighted differences between two devices,” noted Dr. Corcos, “both with untested features in need of further investigation........Obtape, which initially showed promised as an effective treatment alternative to TVT, was pulled from the market following reports of significantly higher rates of erosion compared to other trans-obturator tapes. Dr. Corcose noted that tapes such as Obtryx and Arix, which are distributed to urologists worldwide, have not been formally studied and don’t appear to have been investigated for safety and efficacy.Dr. Corcos urged colleagues to carefully assess how easily any bio-prosthetic material can be removed. “This is a basic surgical principle,” he noted, that must be observed given “…the significant difficulty of surgical removal in the setting of deep space infections.”
Although partial resection is the recommended surgical approach for vaginal erosions, “the possibility of leaving behind infected portions of mesh is real,” said Dr. Corcos. As a result, many women may present with late-onset deep space infections that ultimately require radical debridement.
Surg Innov. 2005 Mar;12(1):63-9.
The argument for lightweight polypropylene mesh in hernia repair.Cobb WS1, Kercher KW, Heniford BT.
Author information:AbstractThe development of polypropylene prosthetics revolutionized surgery for the repair of abdominal wall hernias. A tension-free mesh technique has drastically reduced recurrence rates for all hernias compared to tissue repairs and has made it possible to reconstruct large ventral defects that were previously irreparable. The repair of abdominal wall defects is one of the most commonly performed general surgical procedures, with over 1 million polypropylene implants inserted each year. Surprisingly, little research has been performed to investigate the interaction of abdominal wall forces on a ventral hernia repair or the required amount or strength of the foreign-body material necessary for an adequate hernia repair. The long-term consequences of implantable polypropylene prosthetics are not without concern. The body generates an intense inflammatory response to the prosthetic that results in scar plate formation, increased stiffness of the abdominal wall, and shrinkage of the biomaterial. Reducing the density of polypropylene and creating a ''light weight'' mesh theoretically induces less foreign-body response, results in improved abdominal wall compliance, causes less contraction or shrinkage of the mesh, and allows for better tissue incorporation. A review of the laboratory data and short-term clinical follow-up is reviewed to provide a strong basis or argument for the use of ''light weight'' prosthetics in hernia surgery.
PMID: 15846448 [PubMed - indexed for MEDLINE]
http://www.hindawi.com/journals/ogi/2013/356960/
Obstetrics and Gynecology International
Volume 2013 (2013), Article ID 356960, 7 pages
http://dx.doi.org/10.1155/2013/356960
Review Article
The Role of Vaginal Mesh Procedures in Pelvic Organ Prolapse Surgery in View of Complication RiskDavid R. Ellington and Holly E. Richter
Division of Urogynecology and Pelvic Reconstructive Surgery, Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL 35233, USA Received 26 January 2013; Accepted 29 July 2013 Academic Editor: Stephen Jeffery
Copyright © 2013 David R. Ellington and Holly E. Richter. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
"in the wake of increased medical industry product withdrawal, growing medical and legal concerns, patient safety, and clinical practice controversy, many gynecologists and pelvic reconstructive surgeons are left with limited long-term data, clinical guidance, and growing uncertainty regarding the role of synthetic transvaginal mesh use in pelvic organ prolapse."
http://tvtno.org/wp-content/uploads/2012/06/dr-phillippe-zimmern.pdf
Dr. Phillipe Zimmern............long term studies needed
http://www.ncbi.nlm.nih.gov/pubmed/15846448
Surg Innov. 2005 Mar;12(1):63-9.
The argument for lightweight polypropylene mesh in hernia repair.Cobb WS1, Kercher KW, Heniford BT.
Author information :AbstractThe development of polypropylene prosthetics revolutionized surgery for the repair of abdominal wall hernias. A tension-free mesh technique has drastically reduced recurrence rates for all hernias compared to tissue repairs and has made it possible to reconstruct large ventral defects that were previously irreparable. The repair of abdominal wall defects is one of the most commonly performed general surgical procedures, with over 1 million polypropylene implants inserted each year. Surprisingly, little research has been performed to investigate the interaction of abdominal wall forces on a ventral hernia repair or the required amount or strength of the foreign-body material necessary for an adequate hernia repair. The long-term consequences of implantable polypropylene prosthetics are not without concern. The body generates an intense inflammatory response to the prosthetic that results in scar plate formation, increased stiffness of the abdominal wall, and shrinkage of the biomaterial. Reducing the density of polypropylene and creating a ''light weight'' mesh theoretically induces less foreign-body response, results in improved abdominal wall compliance, causes less contraction or shrinkage of the mesh, and allows for better tissue incorporation. A review of the laboratory data and short-term clinical follow-up is reviewed to provide a strong basis or argument for the use of ''light weight'' prosthetics in hernia surgery.
http://link.springer.com/article/10.1007/s00192-011-1597-7/fulltext.htmlThe mesh debate : Peter L. Dwyer1 and Paul Riss2
(1)Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Melbourne, Australia
(2)Department of Gynecology and Obstetrics, Landesklinikum Thermenregion Moedling, Sr. Maria Restituta Gasse 12, 2340 Moedling/Vienna, Austria
Peter L. Dwyer (Corresponding author)
Email: [email protected]
Paul Riss Email: [email protected]
Published online: 16 November 2011
Without Abstract
The U.S. Food and Drug Administration (FDA) published a second warning to medical practitioners and patients on “Complications Associated with Transvaginal Placement of Surgical Mesh for Pelvic Organ Prolapse” in July 2011. Following this, on the advice of legal advisors the research and ethics committee of one of our hospitals (P.L.D) recommended that no further synthetic mesh be used for any incontinence or prolapse surgery. This recommendation was a case of “throwing the baby out with the bath water” and was not ratified following further discussion. However, it is an indication of the perfect storm referred to by Brubaker and Shull in this issue of the International Urogynecology Journal [1]. In order to give a range of opinions we are also publishing in this issue the views of other well-known gynaecologists on the usage of synthetic grafts [2, 3].
http://www.academia.edu/184543/MESH_GRAFTS_AND_KITS_IN_PELVIC_ORGAN_PROLAPSE_SURGERY_WHERE_ARE_WE_NOW
There is very little data availablethat will support the use of kits in primary prolapse surgeryand they should be avoided in women who are not at highrisk for recurrence. Simpler mesh techniques are alsoassociated with complications and should also be avoided in primary prolapse surgery unless the surgeon has reason tosuspect that the patient is at high risk for recurrence.
http://www.hoajonline.com/journals/pdf/2052-6210-1-4.pdf
One ultrasound study evaluating women at 3 months after anterior vaginal mesh placement found severe contraction or shrinkage, defined as a decrease of more than 50% of the size of the mesh, in 9.3% of patients [86]. Some of the survey revealed that mesh durability and complication is very
lower based with short term follow up and of few limited data; however some of the patient who underwent vaginal procedure healed without any problem, but some group experienced life threatening symptom. So large cohort study is desperately needed to infer the number of mesh- augmented vaginal procedures, that are being performed and its future risk and benefit......
nerve damage from mesh:
https://www.facebook.com/notes/links-on-mesh/drhibner-info-regarding-pudendal-neuralgia/559638800756313
Nerve entrapment involving mesh requires lengthy surgery. While other surgeons may trim the mesh, I firmly believe in removing all the mesh because we cannot determine which part of the mesh is causing pain.
Outcomes data from France show that approximately 30%-40% of patients are pain free after surgical decompression, with another 30% reporting improvement in pain and 30% reporting no change in their pain levels (Eur. Urol. 2005;47:403-8).
At our institution, using national scientific standards for the reporting of pain and extent of pain improvement, we have found that 70% of patients who undergo transgluteal surgical decompression have at least a 20% improvement in pain. Within this broad category are a significant number of patients who are pain free, and many who report improvements of 50% or more.
Interestingly, we have found that outcomes are similar among our much smaller number of "re-do" surgical patients. Thus far we have performed approximately 20 such transgluteal procedures – 17 on patients who had re-scarring of the nerve after surgery performed at other institutions, and 3 who had surgery many years ago in our practice, before we were able to optimally visualize the entire nerve and before we made modifications to improve the procedure. Just as with our first-time surgeries, approximately 70% of patients who underwent a second procedure had at least a 20% improvement in pain.
In all cases, the pudendal nerve recovers slowly, especially when it has been entrapped and injured for a long time, and improvements in pain often do not occur until about 4 months after surgery. Improvement typically continues for some time, up to 18 months after surgery. Patients may still have pain related to muscle spasms after surgery, so continued physical therapy and/or more Botox injections are often beneficial. Patients must also, of course, continue to avoid any offending factors or activities.
Dr. Hibner is a former fellow in advanced gynecologic surgery at Mayo Clinic, Scottsdale, Ariz., and is now professor of obstetrics and gynecology, Creighton University, Omaha, Neb., and associate clinical professor of obstetrics and gynecology, University of Arizona, Tucson. He also is director of the Arizona Center for Chronic Pelvic Pain, St. Joseph’s Hospital and Medical Center, Phoenix. To review his surgical procedure, visit SurgeryU atwww.aagl.org/mastercourse. Dr. Hibner reported that he has no relevant financial disclosures.
oxidation:
http://dept.lamar.edu/zhanhu/publication/cp.pdf
a b s t r a c t:
Partially water-soluble oxidized regenerated cellulose carboxylate sodium (ORC-Na) materials have been prepared by controlled neutralizing oxidized generated cellulose (ORC). The carboxyl were converted into sodium carboxylate as evidenced by FT-IR, and carboxyl content decreased from 18.41% to 0.98%, with enhancing water solubility of ORC-Na to form gel, and SEM–EDX revealed that the sodium carboxylate groups presented in a gradient distribution from the exterior to the interior of fiber. ORC-Na introduced a new hemostatic mechanism, i.e., forming gel to mechanically seal off the crevasses of vessels. Due to its excellent water solubility and 5.23% carboxyl, ORC-Na-3 possessed optimum hemostatic efficiency and demonstrated a capability to stop bleeding within shortest time (102 and 138 s) with the least blood loss (0.886 and 1.006 g), and implantation test showed ORC-Na-3 could be absorbed in less than 2 weeks with no pathological response remaining. In conclusion, ORC-Na-3 is an efficient hemostat with optimum biodegradability.......Johnson & Johnson has pioneered an industrial scale oxidationprocess using nitrogen dioxide to manufacture ORC absorbable haemostat (Domb, Kost, & Wiseman, 1998) – Surgicel (Alpaslan,Alpaslan, & Oygur, 1997; Ashworth & Whear, 2003; Breech & Laufer, 2000; Loescher & Robinson, 1998; Sharma & Malhotra, 2006; harma, Malhotra, & Pundir, 2003). In recent decades, commercial Surgicel absorbable hemostatic agent has been widely applied in various surgeries and played an important role on stopping the bleeding. Although this hemostatic material is broadly applied due to its excellent properties, the commercial ORC has also shown several inherent disadvantages.For example, the hemostatic property of this material is relatively poor and has a low biodegradability. With a carboxyl content ranging from 16% to 24% and a ph of approx 3.1ORC would damage the nervous system if this material is implanted in the human body.
http://www.medscape.com/viewarticle/806408_4
Safety of Oxidized Regenerated Cellulose Although oxidized regenerated cellulose products are rapidly cleared from the implant site and are generally safe and well-tolerated, save for a few complications associated with neurosurgical use, some adverse reactions have been reported. Rare reports of granulomatous foreign-body reactions that mimic brain tumor recurrence or hematoma have been described in patients who had undergone surgical brain tumor resection.[11,19,20] All were removed surgically with positive results, and histologically, most comprised cellulose remnants in addition to monocytes and multinuclear giant cells. Additionally, there have been reports of paralysis and nerve damage when oxidized regenerated cellulose was used around, in, or in proximity to, foramina in bone, areas of bony confine, the spinal cord, and/or the optic nerve or chiasm (Table 1).
In cases of swelling of the oxidized regenerated cellulose, nerve compression and damage was only partially reversible upon reoperation and removal. Therefore, it is recommended that Product A be removed whenever possible after hemostasis is achieved. This is particularly true when the product is applied in confined areas[21,29] (Table 1).
In accordance with its labeled indications, the Product A family of hemostats should not be used to control hemorrhage from large arteries. Rather, it should be used as an adjunct to ligation or other conventional methods to control capillary, venous, and small arterial hemorrhage. To avoid complications, it should not be closed in a contaminated wound without drainage. One of the advantages of oxidized regenerated cellulose is that it is plant-derived, and thus contains no human components.[21] Therefore, there is no risk of viral disease (eg, human immunodeficiency virus) transmission.
oxidation of PP:
http://www.ncbi.nlm.nih.gov/pubmed/20052576Int Urogynecol J. 2010 Mar;21(3):261-70. doi: 10.1007/s00192-009-1021-8. Epub 2010 Jan 6.
Polypropylene as a reinforcement in pelvic surgery is not inert: comparative analysis of 100 explants.Clavé A1, Yahi H, Hammou JC, Montanari S, Gounon P, Clavé H.Author informationAbstract: INTRODUCTION AND HYPOTHESIS:Currently, most implants used for reinforcement in surgical treatment of pelvic floor disorders are knitted monofilament polypropylene (PP). While previously recognized as inert, PP is associated with high complication rates. Some recent literature suggests polyester prosthetics based on poly(ethylene terephthalate) (PET), which may be more inert in vivo. METHODS:A sample of 100 implants explanted from patients due to complications was examined to evaluate the relative degradation characteristics of PP and PET prosthetics. Histological, microscopic (scanning electron microscopy, SEM) and chemical analysis (Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC)) were conducted on these explants. RESULTS:Poly(ethylene terephtahlate) explants appeared to sustain less degradation in vivo than the PP explants observed in this cohort. CONCLUSIONS:This is the first study to evaluate synthetic implants used in a vaginal approach for pelvic floor reinforcement. The study provides evidence contrary to published literature characterizing PP as inert in such applications. Additionally, the study suggests the need for clinical trials comparatively investigating the performance of new types of monofilament prosthetics, such as those comprising PET.PMID: 20052576 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/6474110
Analytical, occupational and toxicologic aspects of the degradation products of polypropylene plastics.Frostling H, Hoff A, Jacobsson S, Pfäffli P, Vainiotalo S, Zitting A. Abstract: Thermooxidative degradation of polypropylene (PP) at close to the industrial processing temperatures was studied with thermogravimetric analysis, infrared spectroscopy, and gas chromatography-mass spectrometry (GC-MS). GC-MS allowed identification of 47 volatile degradation products. Formaldehyde, acetaldehyde, alpha-methylacrolein, acetic acid, and acetone were the major products. Antioxidants markedly slowed down the degradation of polypropylene and the evolution of the degradation products. The relative amounts of the oxidized products were mostly independent of the degradation temperature or the type of antioxidant. Measurements in the plastics industry revealed low airborne concentrations of individual volatile products. The concentration of aerosols, which infrared analysis showed to resemble paraffin fumes, was significant and probably the most important hygienic hazard. The biochemical parameters (the consumption of protecting sulfhydryl groups and the effects on foreign compound metabolism) indicated that the degradation products are biologically reactive, affecting the balance of normal metabolism in exposed animals.
PMID: 6474110 [PubMed - indexed for MEDLINE] Free full text
http://www.geotextile.com/downloads/Propex%20EB-405%20Durability%20of%20Polypropylene.pdf
Polypropylene oxidation is the reaction of free radicals within the polymer with oxygen, resulting in breakdown and/or degradation of the molecular chains and embrittlement of the polymer.
http://cdn.intechopen.com/pdfs/37233/InTech-Thermal_oxidation_of_polypropylene_and_modified_polypropylene_structure_effects.pdf
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112322/
Degradation, infection and heat effects on polypropylene mesh for pelvic implantation: what was known and when it was known, Donald R. Ostergard
ProteGen® Sling Mesh Kit FDA Clearance Letter Dated November 15, 1996
- Multifilament Surgipro® mesh has more FBGCs than monofilament PP mesh [19].
- High and low responders indentified by tumor necrosis factor measurements [20].
- Bacteria adhere to biomaterials using a biofilm [21].
- PP mesh shrinks 30-50% after 4 weeks [22].
- A multifilament mesh must be removed with infection [23].
- Surface roughness promotes wicking of bacteria [24].
- Ten bacterial colony forming units are enough to infect 15% of multifilament meshes [25].
- Bacterial colonization found in 33% of explanted meshes [26].
SPARC® FDA Clearance Letter Dated October 26, 2001
- Greater pore size leads to more deposition of mature collagen with increased tensile strength and vascularity. Pores <12 microns prevent vascularization [27].
- The abdominal wall stiffens after mesh insertion [28].
- The extent of bacterial adherence depends on the mesh surface area. Multifilament meshes have a 205% increase in surface area compared to monofilament meshes. This may explain infection months to years after implantation [29].
- Heat sterilization causes degradation [30]. Figures 1 and and22.
Polypropylene:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112322/ Degradation, infection and heat effects on polypropylene mesh for pelvic implantation: what was known and when it was knownDonald R. Ostergard
http://www.ncbi.nlm.nih.gov/pubmed/10149078J Appl Biomater. 1991 Summer;2(2):73-94. Performance of the polypropylene fiber tailstring on the Copper 7 intrauterine device.Warner MS1, Matsuno SJ, Virgin CJ Jr, Masterson KB, Schneider GA, Wright TE, Robertson CR, Fives-Taylor P.Author information
Abstract: New and used polypropylene tailstrings from the Copper 7 (Cu-7) intrauterine device were examined by a combination of analytical techniques. Optical microscopy, scanning acoustic and electron microscopy, x-ray diffraction, energy dispersive x-ray analysis, and chemical etching were employed to elucidate both the surface and interior morphology of new Cu-7 tailstrings. Tailstrings removed from women following varying periods of use were investigated with optical microscopy, scanning and transmission electron microscopy. In addition, a subset of the used tailstrings were cultured to identify the types of microorganisms associated with them. Our findings show that unused Cu-7 tailstrings are in various stages of degradation owing to a combination of factors which include the high-draw ratio employed during manufacturing, the method of packaging, and the use of a particulate colourant. Furthermore, it is evident that used Cu-7 tailstrings undergo major deterioration while in situ because of the unfavorable interactions between the highly drawn polypropylene and the physiological environment. These results indicate that the polypropylene tailstrings as manufactured for use with the Cu-7 IUD fail to meet accepted design criteria for biomedical implants. Comment in
- Performance of the polypropylene fiber tailstring. [J Appl Biomater. 1992]
- Concerning "Performance of the polypropylene fibre tailstring on the Copper 7 intrauterine device". [J Appl Biomater. 1991]
http://www.ncbi.nlm.nih.gov/pubmed/20052576
Int Urogynecol J.
2010 Mar;21(3):261-70. doi: 10.1007/s00192-009-1021-8. Epub 2010 Jan 6.
Polypropylene as a reinforcement in pelvic surgery is not inert: comparative analysis of 100 explants.Clavé A1, Yahi H, Hammou JC, Montanari S, Gounon P, Clavé H. Author information Abstract : INTRODUCTION AND HYPOTHESIS:Currently, most implants used for reinforcement in surgical treatment of pelvic floor disorders are knitted monofilament polypropylene (PP). While previously recognized as inert, PP is associated with high complication rates. Some recent literature suggests polyester prosthetics based on poly(ethylene terephthalate) (PET), which may be more inert in vivo.............
http://en.wikipedia.org/wiki/Polypropylene
Chemical and physical properties[edit] Micrograph of polypropylene:
Most commercial polypropylene is isotactic and has an intermediate level of crystallinity between that of low-density polyethylene (LDPE) and high-density polyethylene (HDPE). Polypropylene is normally tough and flexible, especially when copolymerized with ethylene. This allows polypropylene to be used as an engineering plastic, competing with materials such as ABS. Polypropylene is reasonably economical, and can be made translucent when uncolored but is not as readily made transparent as polystyrene, acrylic, or certain other plastics. It is often opaque or colored using pigments. Polypropylene has good resistance to fatigue. The melting point of polypropylene occurs at a range, so a melting point is determined by finding the highest temperature of a differential scanning calorimetry chart. Perfectly isotactic PP has a melting point of 171 °C (340 °F). Commercial isotactic PP has a melting point that ranges from 160 to 166 °C (320 to 331 °F), depending on atactic material and crystallinity. Syndiotactic PP with a crystallinity of 30% has a melting point of 130 °C (266 °F).[2] The melt flow rate (MFR) or melt flow index (MFI) is a measure of molecular weight of polypropylene. The measure helps to determine how easily the molten raw material will flow during processing. Polypropylene with higher MFR will fill the plastic mold more easily during the injection or blow-molding production process. As the melt flow increases, however, some physical properties, like impact strength, will decrease. There are three general types of polypropylene: homopolymer, random copolymer, and block copolymer. The comonomer is typically used with ethylene. Ethylene-propylene rubber or EPDM added to polypropylene homopolymer increases its low temperature impact strength. Randomly polymerized ethylene monomer added to polypropylene homopolymer decreases the polymer crystallinity and makes the polymer more transparent.
Degradation[edit] Polypropylene is liable to chain degradation from exposure to heat and UV radiation such as that present in sunlight. Oxidation usually occurs at the tertiary carbon atom present in every repeat unit. A free radical is formed here, and then reacts further with oxygen, followed by chain scission to yield aldehydes and carboxylic acids. In external applications, it shows up as a network of fine cracks and crazes that become deeper and more severe with time of exposure. For external applications, UV-absorbing additives must be used. Carbon black also provides some protection from UV attack. The polymer can also be oxidized at high temperatures, a common problem during molding operations. Anti-oxidants are normally added to prevent polymer degradation. Microbial communities isolated from soil samples mixed with starch have been shown to be capable of degrading polypropylene.[3]
History[edit] PMID: 20052576 [PubMed - indexed for MEDLINE] http://en.wikipedia.org/wiki/Polypropylene
Oxidation usually occurs at the tertiary carbon atom present in every repeat unit.
A free radical is formed here, and then reacts further with oxygen, followed by chain scission to yield aldehydes and carboxylic acids.In 2008, researchers in Canada asserted that quaternary ammonium biocides and oleamide were leaking out of certain polypropylene labware, affecting experimental results.
PP resin additives;
http://www.ampacet.com/faqs/reasons-for-using-antiblock-additives/
silica, talc, calcium carbonate, synthetic silica, ceramic spheres, kaolin/clay, mica
http://www.inchem.org/documents/kemi/kemi/ah1998_12.pdf
Polypropylene is processed by methods very similar to those for polyethylenes
(see section 1.2). Most processing operations use melt temperatures in the range
210–250°C, and because polypropylene is easily oxidised, the heating is kept
down to a minimum (5).
http://globe-tek.com/polypropylene
Polypropylene is liable to chain degradation from exposure to UV radiation such as that present in sunlight. Oxidation usually occurs at the secondary carbon atom present in every repeat unit. A free radical is formed here, and then reacts further with oxygen, followed by chain scission to yield aldehydes and carboxylic acids. In external applications, it shows up as a network of fine cracks and crazes which become deeper and more severe with time of exposure......Polypropylene has been used in hernia and pelvic organ prolapse repair operations to protect the body from new hernias in the same location. A small patch of the material is placed over the spot of the hernia, below the skin, and is painless and is rarely, if ever, rejected by the body. However the FDA has issued several warnings on the use of polypropylene mesh medical kits when used for certain applications in pelvic organ prolapse, specifically when introduced in close proximity to the vaginal wall due to a continued increase in number of mesh erosions being reported by patients over the past few years.
(obviously globe-tek has not availed themselves to the information that a large % of hernia patients have chronic pain after being implanted with polypropylene mesh)
http://books.google.ca/books?id=9TA_AAAAQBAJ&pg=PA155&lpg=PA155&dq=medical+mesh+flaking&source=bl&ots=d52A1wlfZl&sig=-M3USgHXu6vxxcOxyQO-I0tEU88&hl=en&sa=X&ei=3IZQU8HtEI-MyAGxx4C4DQ&redir_esc=y#v=onepage&q=medical%20mesh%20flaking&f=falseManagement of Abdominal Hernias: ..polypropylene, polyester...will initiate a biological or chemical response...
proper patient selection:
http://www.hoajonline.com/gynecology/2052-6210/1/4
Before recommending the technique for general use in all Prolapse patients, a lot of things like investigation on proper patient selection, continue research on graft composition, techniques that minimize complications of needle passes or mesh placement should be understood thoroughly. Apart from these we still should have more surgical skills to perform the procedures, to reduce complications and increase better results.
pudendal and other pelvic nerve damage:
http://emedicine.medscape.com/article/1234809-overview#aw2aab6b3
Nerve Entrapment Syndromes of the Lower Extremity
Updated: Oct 22, 2012
EtiologyThe obturator nerve is rarely injured in isolation. However, injury can occur with pelvic trauma and associated fractures, during delivery as a result of compression of the nerve between the head of the fetus and the bony structures of the pelvis, or as a consequence of compression of the nerve between a tumor and the bony pelvis. Entrapment may also occur in the obturator canal during surgery or with total hip arthroplasties. Other potential causes include malposition of the lower limb for prolonged periods, entrapment in the adductor magnus in athletes, and abnormal positioning of the lower limb of a newborn during a difficult delivery. Some physicians believe that the anterior branch may be entrapped in the fascia as it passes over the adductor brevis muscle, owing to an inflammatory process.[16........................
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183551/
The differential diagnosis of persistent pelvic pain can include muscle strain, osteitis pubis, inflammation, or nerve entrapment. This report explores the first reported cases of “De Novo Pudendal Neuropathy” in 5 individuals who had a TOT-O procedure. Stedman's Medical Dictionary14 defines neuropathy as any disturbance or pathologic changes in the nervous system. Peripheral neuropathy is a problem with the nerves that carry information to and from the brain and spinal cord. This problem can produce pain, loss of sensation, and an inability to control muscles.15.... . Often there is a pain sensation occurring with a particular stimulation, which usually does not cause discomfort, or there can be an unpleasant or exaggerated prolonged pain response. Symptoms of pudendal nerve entrapment are often exaggerated while sitting. Standing can often relieve these symptoms. When one is lying down or “sitting on a toilet seat,” these symptoms are usually absent. This was seen in most of our patients. Sexual dysfunction and bowel or bladder changes can often accompany the problems.28,29
http://commonhealth.wbur.org/2011/11/surgery-under-scrutiny-what-went-wrong-with-vaginal-mesh
But rather than fix their problems, the mesh led to a range of far more awful complications. For some, the material eroded through the vaginal lining, causing infections and nerve damage, as well as excruciating pain, the inability to sit down or urinate without a catheter, multiple hospitalizations and a halt to their sex lives.
http://www.iuga2013.com/handouts/docs/handout25_hgoldman.pdf
with TVT complications removal of sling may cause more trauma and not resolve pain
http://www.meshsurgeons.com/casestudy20.php
Comment Dr. Moore: If there are signs of a pudendal neuropathy (on either side) these can be caused by one of the mesh arms that are placed through the sacrospinous ligament. The nerve can be injured during placement or it can be placed too tight or heal under tension. This can create pulling or scar tissue irritating the nerve. In these cases it usually is not enough to just release the arm. It typically needs to be removed completely out of the ligament and the scar tissue released away from the nerve. This is a very difficult procedure and should only be completed by an expert. The first generation kits that utilize a needle pass through the buttock cheeks (such as Prolift or Avaulta) and pass the arm blindly through the back of the ligament is at risk for this type of complication.
http://dare.uva.nl/document/194631
severe persistent groin pain after uncomplicated TVT-O, in which magnetic resonance imaging and electromyography
did not reveal the cause. We concluded that the tapementrapped or cut through peripheral branches of the
obturator nerve. ... chance that damage to the obturator nerve is reversible, although it is importantto counsel patients with similar pathology that recovery cantake long and may be only partial. Keywords Obturator nerve damage .Pain.Tension-free vaginal tape–obturator.Therapy
severe persistent groin pain after uncomplicated TVT-O, in which magnetic resonance imaging and electromyography did not reveal the cause. We concluded that the tape entrapped or cut through peripheral branches of the obturator nerve.
http://www.pudendalhope.info/node/23 Pudendal Nerve Decompression Surgery
Pudendal Nerve Decompression Surgery ,Pudendal nerve decompression surgery is an option that is usually considered after more conservative therapies such as lifestyle changes,pelvic floor physical therapy, and nerve blocks have not proven to be successful. In the published literature PNE surgery can achieve a success rate of anywhere from 60% to 85% but success does not necessarily mean a cure. Surgery is generally considered successful if there is at least a 50% reduction in pain and symptoms.
recalled:
http://commonhealth.wbur.org/2011/11/surgery-under-scrutiny-what-went-wrong-with-vaginal-mesh
But new questions about the FDA’s “clearance” process are now being raised. A recent Bloomberginvestigation reports on a vaginal mesh device made by Johnson & Johnson (as well as mesh from other companies) “cleared” by the FDA based on its equivalence to an older product that was recalled in 1999: Boston Scientific’s ProteGen Sling. (J&J, which is facing lawsuits over vaginal mesh, told Bloomberg its mesh products are safe.) The ProteGen “had never been implanted in a human vagina prior to its clearance,” wrote urogynecologist L. Lewis Wall, a professor at Washington University School of Medicine in St. Louis in an article published in the American Journal of Obstetrics and Gynecology.” The ProteGen, for stress urinary incontinence, was recalled due to its high complication rate; the FDA called it a “misbranded” and “adulterated” product, according to a 2002 investigation published in the New Jersey Star-Ledger. (I contacted Boston Scientific with more questions about this but they did not provide answers.)
http://www.urogynecologist.com/images/The_perils_of_commercially_driven_surgical_innovation.pdf
Over 23,000 unused (unimplanted) kits wererecalled, but patients who had already had a ProteGen Sling implanted were“left to their own devices.”
sexual function post mesh :
http://www.academia.edu/184543/MESH_GRAFTS_AND_KITS_IN_PELVIC_ORGAN_PROLAPSE_SURGERY_WHERE_ARE_WE_NOW
Of major concern is the fact that sexual function isnotoriously underreported. De-novo dyspareunia rates of up to 36% following the use of non-absorbable synthetic meshhave been reported.5 Extreme care should be exercised when using synthetic grafts in sexually active women.....De novo dyspareunia rates in two case series ranged from 6% following combined synthetic mesh insertion to 16%following absorbable biological graft insertion. Milan et al have however reported a 63% increase in dyspareunia rates following posterior synthetic mesh insertion.
sterilization concerns of surgical mesh:
http://www.sterigenics.com/residual.htm
Residual Testing:When a product is sterilized with ethylene oxide (EO), some of the gas may be absorbed by the product and/or its packaging and retained after sterilization. There may also be traces of EO bi-products present after sterilization. The extent of degassing and aeration used during the sterilization process will have a significant effect in reducing these residue levels.
Why you need it....Residual testing is your assurance that your product is safe to market
Determining the levels of EO and its by-products is a requirement for many medical devices. The International Standard (ISO) 10993-7 describes the categorization of products, methods of residual testing and allowable limits of residues SteriPro® Laboratories provide:
The Simulated Use Method extracts residues over a set time based on the maximum time thedevice would be exposed to a patient, and the route by which any dose would be administered.
The Exhaustive Extraction Method extracts residues by heating the product in a sealed systemand testing the vapour above it, by repeated aqueous extraction of the samples. SteriPro® Labs Brochure
http://www.ncbi.nlm.nih.gov/pubmed/21168702
Ethylene oxide allergy in patients on hemodialysis waiting for kidney transplantation: logistical nightmare or challenge? A case report.Monbaliu D1, Van Breussegem A, Onsia A, Vandermeersch E, Segers C, Meert W, Kochuyt AM, Pirenne J, Claes K.
Author information
Abstract : Ethylene oxide (EO) is widely used as a sterilization gas for heat-sensitive devices. In EO-sensitized patients, this type of sterilization can cause rare but major allergic reactions such as hives, rash, asthma, or anaphylactic shock. Hemodialysis patients in particular are at risk of developing hypersensitivity to EO. In these patients, surgical interventions should be planned far in advance allowing a thorough EO-free preparation of all equipment needed for the surgery as well as for the pre-, peri-, and postoperative care. In contrast to elective surgery, kidney transplantation with allografts from deceased donors cannot be planned; exact timing is unpredictable. Furthermore, transplantation may take place years after patients have been put on the waiting list. Listing of patients sensitive for EO is therefore a logistical and medical challenge for all health care professionals involved in the patient's care (eg, surgeons, nephrologists, anesthetists, nurses, pharmacists, and sterilization specialists). This case report describes a patient with chronic kidney disease stage V who developed EO allergy during hemodialysis while waiting for a kidney transplantation. Diagnosis was made based on clinical signs and confirmed biochemically (including a positive radioallergosorbent test). Because the only treatment is avoidance of contact with EO-sterilized materials, a strict EO-free protocol was developed to allow an uneventful transplantation thereafter. Subsequently, 4 newly diagnosed EO-sensitive patients on the active kidney transplantation waiting list were diagnosed, and 1 of these patients has been transplanted successfully. EO allergy in patients on the waiting list for kidney transplantation is a unique challenging situation which, to the best of our knowledge, has not been reported yet for kidney transplantation. This report further highlights the logistical preparation of a renal transplantation, including anesthesiologic, surgical, and postoperative care.
Copyright © 2010 Elsevier Inc. All rights reserved.
PMID: 21168702 [PubMed - indexed for MEDLINE]
http://biotextiles2013.wordpress.com/hernia_repair_mesh/
Ethylene Oxide (ETO) Sterilization
The process of ethylene oxide sterilization consists of the product being left to soak in a corrosive gas. After soaking in the corrosive gas the product is extracted and completely sterile. This sterilization method is done in batches taking around 4-5 hours a piece and is often repeated several times. This causes the sterilization to be a timely process.
Advantages
- Variety of Materials possible
- Ease of packaging and shipping
- Low Design Expense
- Packaging used must be permeable
- Aeration must occur
- If aeration doesn’t occur the product may not become fully sterile
- Toxic chemicals
- Small traces of ETO on the product after processing
- Takes one to two weeks
- The vacuum, pressure, temperature, time, humidity, and ETO concentration can effect how sterile the product becomes
https://www.osha.gov/OshDoc/data_General_Facts/ethylene-oxide-factsheet.pdf
What is ethylene oxide? Ethylene oxide (EtO) is a flammable, colorless gas at temperatures above 51.3 ºF (10.7 ºC) that smells like ether at toxic levels. EtO is found in the production of solvents, antifreeze, textiles, detergents,adhesives,polyurethane foam, and pharmaceuticals. Smaller amounts are present in fumigants, sterilants for spices and cosmetics, as well as during hospital sterilization of surgical equipment. How can ethylene oxide harm workers? In addition to eye pain and sore throat, exposure toEtO can cause difficult breathing and blurred vision.Exposure can also cause dizziness, nausea, headache,convulsions, blisters and can result in vomiting and coughing. Both human and animal studies show that EtO is a carcinogen that may cause leukemia and other cancers. EtO is also linked to spontaneous abortion, genetic damage, nerve damage, peripheral paralysis, muscle weakness, as well as impaired thinking and memory. In liquid form, EtO can cause severe skin irritation upon prolonged or confined contact.
http://www.inchem.org/documents/ehc/ehc/ehc55.htm#SubSectionNumber:4.2.2
Although the evidence for the carcinogenicity of ethylene oxide in man is inadequate, epidemiological studies indicate that exposure to ethylene oxide (in mixtures with other chemicals) increases the risk of malignancies (section 8.6). Although the evidence for the carcinogenicity of ethylene oxide in man is inadequate, epidemiological studies indicate that exposure to ethylene oxide (in mixtures with other chemicals) increases the risk of malignancies (section 8.6).
( so most synthetic meshes appear to be sterilized with the carcinogenic substance ethylene oxide .... and we are told that that the gases after being vented leave no harmful levels of ethylene oxide residues ....... but as we all know accidents happen, equip .fails, man made errors may occur )
( are patients with systemic reactions to synthetic mesh sterilized with EO only reacting to the known adverse properties of polypropylene mesh ? )
http://www.ncbi.nlm.nih.gov/pubmed/7154883
[Absorption of ethylene oxide by medical polymers].[Article in Russian]
Likhtman TV, Komarkova NI, Kareev NV.
AbstractThe balanced sorption of a sterilizing gas--ethylene oxide (EO)--by medical polymers most commonly used in medical industry is studied. These polymers are compositions on the base of polyvinylchloride (PVC), polyethylene (PE), natural and silicone rubbers. The absorption coefficients for EO and the above materials are calculated. The most sorption capacity is inherent in the PVC-based compositions and the least one--in the PE-based materials. The latters as well as silicone rubber materials are recommended for medical engineering products subjected to gaseous sterilization.
PMID: 7154883 [PubMed - indexed for MEDLINE]
surgical ethics:
http://www.urogynecologist.com/images/The_perils_of_commercially_driven_surgical_innovation.pdf
Nevertheless, it is clear that powerful commercial interests are reshaping the field of pelvic surgery.....Acceptance as a “standard procedure”—the procedure has now become entrenched. Case series accumulate, but formal critical evaluation still does not exist. Powerful forces— both surgical egos and commercial interests— champion the procedure and discourage criticism....The randomized controlled trial—inquiring minds finally decide to evaluate the procedure in a formal study.. Professional denunciation of the procedure—the randomized controlled trial finds the procedure wanting...What has happened in this country is the development of a disjunction between legal permission to sell a product and the prudent ethical use of those products by surgeons ...
testing for biocompatibilty: what leads do we have ?
http://www.ncbi.nlm.nih.gov/m/pubmed/10430710/
These results provide evidence that HLA phenotype is a significant determinant of sensitization to complex platinum salts and for the first time show that the strength of this association varies with intensity of exposure to the sensitizing agent. They imply that as exposure-control measures are taken to prevent occupational sensitization and, by analogy, sensitization to allergens outside the
workplace,disease incidence will increasingly be determined by genetic susceptibility. ( could this sensitization apply to synthetic mesh ?)
http://www.qeesi.org/Claudia S. Miller, MD, MS, is an allergist/immunologist and tenured professor at the University of Texas School of Medicine at San Antonio. She researches the underlying environmental causes of disease and teaches the prevention, diagnosis and treatment of environmentally-induced or exacerbated illnesses. Her work led to the development of the most widely used screening instrument for chemical intolerance, the QEESI, and revealed a new disease process called Toxicant-induced Loss of Tolerance, or TILT.
http://books.google.ca/books?id=7L8EK4mU0ikC&pg=PA384&lpg=PA384&dq=polymeric+biomaterials,+volume+1+introduced+into+the+body+of+a+specific+individual+without+exciting+a+destructive+reaction%E2%80%9D&source=bl&ots=wtrTIATQDd&sig=sdMbU4R1fRT5ngUa8qcbqGzx7xU&hl=en&sa=X&ei=BZEfU7-IL6PuyAGLvoGQCQ&ved=0CCwQ6AEwAA#v=onepage&q=polymeric%20biomaterials%2C%20volume%201%20introduced%20into%20the%20body%20of%20a%20specific%20individual%20without%20exciting%20a%20destructive%20reaction%E2%80%9D&f=false
indirect and direct testing ..cytotoxicity.....
Toxins: see leachates
Transvaginal mesh geneology:
http://transvaginalmeshlawsuit.org/transvaginal-mesh-genealogy-rotten/
Transvaginal Mesh Genealogy: Rotten from the Roots UpA few weeks ago we explored the 510(k) process through which medical devices are approved based on similarities to a predicate (older device). In the last post, the problems with the 510(k) process were expounded upon when we discussed SOUND Device Act’s attempt to empower the FDA to actually provide protection from faulty medical devices. The current language of the law prevents the FDA from denying the application of 510(k) devices even when their grandparent devices were problematic and even harmful.
Today’s dangerous transvaginal mesh products used Boston Scientific’s ProteGen Sling as their 510(k) predicate device to force the FDA’s approval. Considering the history of the ProteGen Sling, the issues with transvaginal mesh (TVM) should have been as predictable as they are tragic.
Embarrassing Family HistoryHere is a quick timeline of the short-lived predicate device, the ProteGen Sling.
- 1995: Boston Scientific seeks 510(k) approval for a synthetic sling to treat urinary stress incontinence. They cite the use of the fabric for cardiovascular grafts as well as in a 90-day rat study. The material has never before been used in urological operations.
- November 15, 1996: The FDA grants approval of the sling, despite no human testing demonstrating its efficacy and safety.
- April 1997: The ProteGen Sling is unveiled at the American Urological Association’s spring convention. By this point, the device has already been on the market for a few months.
- June 1998: The FDA inspects one of the ProteGen Sling plants. The results are far from comforting, as they discover that Boston Scientific has reported only the cases in which the sling had to be removed (not all other complications) and that 30 percent of complaints made have simply not been reported.
- Jan. 22, 1999: Six months after the FDA inspection, Boston Scientific officially recalls the ProteGen Sling.
Progeny of the ProteGen SlingAlthough the ProteGen Sling was on the market short of two years, the affair lasted long enough for Johnson & Johnson to use it as the 510(k) predicate for its own bladder sling, the Gynecare TVT, which was approved by the FDA in 1998.
From ProteGen, a device that itself slipped through the cracks of the 510(k) system, came a whole family of bladder slings, which in turn spawned transvaginal mesh for pelvic organ prolapse repair. The fruits of this family? Thousands of women who suffer daily, have undergone multiple painful surgeries to varying degrees of success and who are in no better, and in many cases far worse, condition than they were before their TVM implant.
Where Does it Stop?Manufacturers have been knowingly modeling mesh devices after faulty products for over a decade. They continue with product development and marketing without addressing these serious safety issues, despite the constant influx of tragic stories of lives ruined by TVM. Why? Perhaps because they can.
The FDA cannot deny the 510(k) requests and has not issued official recalls of TVM devices. Thousands of women and their families, however, have begun to speak out and take TVM manufacturers to court to hold them responsible for the damage done by their products. Get the word out: Share this blog; tell your story; demand justice.
ultra sound imaging to assess mesh location and stability:
http://www.ultrasonix.com/blog/blog-dr-mueller-uses-ultrasound-to-identify-surgical-mesh
http://link.springer.com/chapter/10.1007%2F978-88-470-1542-5_8#page-1
Translabial or transperineal ultrasound is fast becoming the standard imaging method for the assessment of women with symptoms of lower urinary tract dysfunction and pelvic organ prolapse. Three/four-dimensional (3D/4D) imaging has greatly added to the utility of the method, and suitable equipment is becoming widely available. This chapter describes the technical requirements and equipment as well as the basic and advanced methodology of 2D-, 3D-, and 4D-ultrasound in the investigation of pelvic floor and lower urinary tract disorders.
http://www.sauga.org.za/Professional/Reviews/dietz.pdf
Key words: female pelvic organ prolapse, levator ani, pelvic floor, 3-dimensionalultrasound, translabial ultrasound. ....Ultrasoundis the only imaging method able to visualize modern mesh slings and implants
http://arg.co.nz/about/profile/helen-moore/
for patients in NZ this is a patient endorsed resource for imaging of mesh
warnings:
http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2010/surgical-mesh_nth-aah-eng.php
Health Canada Warning
http://commonhealth.wbur.org/2011/11/surgery-under-scrutiny-what-went-wrong-with-vaginal-mesh
Deleting The Word ‘Experimental’ In A Bulletin
If not for a controversial shift in an influential professional group publication, vaginal mesh surgery might have had a harder time gaining popularity. And some physicians say the underlying force behind the procedure’s spread is money. Back in February 2007 — before FDA’s public health alert — the American College of Obstetricians and Gynecologists issued a clinical practice bulletin on pelvic organ prolapse.
The February bulletin warned doctors and patients to consider the vaginal mesh procedure to be “experimental.” It said: “Given the limited data and frequent changes in marketed products (particularly with regard to type of mesh material itself, which is most closely associated with several of the postoperative risks, especially mesh erosion), the procedures should be considered experimental and patients should consent to surgery with that understanding.” (Bold is mine). Seven months later, ACOG issued another bulletin on vaginal mesh surgery. This time, the word “experimental” was gone, in favor of what some might consider a softer warning: “Given the limited data and frequent changes in marketed products for vaginal surgery for prolapse repair (particularly with regard to type of mesh material itself, which is most closely associated with several of the postoperative risks, especially mesh erosion), patients should consent to surgery with an understanding of the post-operative risks and lack of long-term outcomes data.
Experimental procedures are often not covered by third-party insurance because evidence of their safety and efficacy is lacking. And two physicians, including one of the primary authors of the original February 2007 bulletin, have said that the threat of losing that insurance money was behind the change in wording.
“I think ACOG was choosing to protect its clinicians’ insurance incomes over patients’ well being,” said urogynecologist Dr. Anne Weber.
Dr. Anne Weber, the urogynecologist and former head of the NIH’s pelvic organ disorder program said that as the prolapse bulletin’s lead author, she vehemently opposed the change in wording. “I think ACOG was choosing to protect its clinicians’ insurance incomes over patients’ well being,” she said in an interview.
http://link.springer.com/article/10.1007/s00192-011-1581-2
International Urogynecology JournalJanuary 2012, Volume 23, Issue 1, pp 5-9
Time to rethink: an evidence-based response from pelvic surgeons to the FDA Safety Communication: “UPDATE on Serious Complications Associated with Transvaginal Placement of Surgical Mesh for Pelvic Organ Prolapse”
http://www.fda.gov/medicaldevices/safety/alertsandnotices/publichealthnotifications/ucm061976.htm
FDA Public Health Notification: Serious Complications Associated with Transvaginal Placement of Surgical Mesh in Repair of Pelvic Organ Prolapse and Stress Urinary IncontinenceFor updated information about Surgical Mesh for Pelvic Organ Prolapse, see: UPDATE on Serious Complications Associated with Transvaginal Placement of Surgical Mesh for Pelvic Organ Prolapse, released July 13, 2011.
Issued: October 20, 2008 Dear Healthcare Practitioner:
This is to alert you to complications associated with transvaginal placement of surgical mesh to treat Pelvic Organ Prolapse (POP) and Stress Urinary Incontinence (SUI). Although rare, these complications can have serious consequences. Following is information regarding the adverse events that have been reported to the FDA and recommendations to reduce the risks.
Nature of the Problem
Over the past three years, FDA has received over 1,000 reports from nine surgical mesh manufacturers of complications that were associated with surgical mesh devices used to repair POP and SUI. These mesh devices are usually placed transvaginally utilizing tools for minimally invasive placement.
The most frequent complications included erosion through vaginal epithelium, infection, pain, urinary problems, and recurrence of prolapse and/or incontinence. There were also reports of bowel, bladder, and blood vessel perforation during insertion. In some cases, vaginal scarring and mesh erosion led to a significant decrease in patient quality of life due to discomfort and pain, including dyspareunia.......................
Reporting Adverse Events to FDA
FDA requires hospitals and other user facilities to report deaths and serious injuries associated with the use of medical devices. If you suspect that a reportable adverse event was related to the use of surgical mesh, you should follow the reporting procedure established by your facility.
We also encourage you to report adverse events related to surgical mesh that do not meet the requirements for mandatory reporting. You can report directly to MedWatch, the FDA Safety Information and Adverse Event Reporting program online, by phone at 1-800-FDA-1088, or obtain the fillable form online, print it out and fax to 1-800-FDA-0178 or mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787.
http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm262435.htm
FDA Safety Communication: UPDATE on Serious Complications Associated with Transvaginal Placement of Surgical Mesh for Pelvic Organ Prolapse
http://www.fda.gov/Safety/MedWatch/default.htm MedWatch: The FDA Safety Information and Adverse Event Reporting Program