R. Rosch

Functional and morphologic properties of a modified mesh for inguinal hernia repair.

Inguinal hernia repair is one of the most frequently performed operations. Next to conventional techniques, open and laparoscopic tension-free methods using mesh implants to reinforce the abdominal wall are increasingly carried out, even becoming the standard procedure in many countries. Because of the benefits of material-reduced meshes for incisional hernia repair, a new mesh modification for tension-free inguinal hernia repair has been developed. In the present study this new low-weight mesh (Vypro II) made of polypropylene and polyglactin multifilaments was compared to a common heavy-weight polypropylene mesh (Prolene) regarding their functional consequences and the morphologic tissue response. After implantation in rats as an inlay, abdominal wall mobility was recorded by three-dimensional photogrammetry and the tensile strength of the suture zone and the mesh itself was measured at 3, 21, and 90 days. Explanted tissue samples have been investigated for their histologic reaction in regard to the inflammatory infiltrate, vascularization, and connective and fat tissue ingrowth. Numbers of granulocytes, macrophages, fibroblasts, lymphocytes, and foreign giant body cells have been evaluated to reflect the quality of the tissue response. The cellular response was assessed by measuring DNA strand breaks and apoptosis (TUNEL), proliferation (Ki67), and cell stress (HSP70). The results indicated that restriction of abdominal wall mobility was significantly reduced with Vypro II compared to that seen with heavy-weight mesh modification, and the inflammatory reaction and connective tissue formation were markedly diminished. Apoptosis and cell proliferation showed considerably lowered levels, and expression of cytoprotective HSP70 was significantly increased. The present study thus confirms the benefits of material-reduced mesh modifications. The new low-weight mesh (Vypro II) could be advantageous in inguinal hernia repair.RésuméLa cure de hernie inguinale est une des interventions les plus pratiquées en chirurgie. A coté des techniques conventionnelles, par voie inguinale ouverte, et sous laparoscopic, des méthodes de cure sans tension, par l’intermédiaire des prothèses pour renforcer la paroi abdominale, sont pratiquées de plus en plus souvent, devenant même le standard dans beaucoup de pays. En raison des bénéfices de ce matériel, on a dévélopé une nouvelle prothèse pour la cure sans tension des hernies inguinales (Vypro II). Dans cette étude, la nouvelle prothèse à poids peu élevé (Vypro II), faite de polypropylene et de multifilaments de polyglactine, comparé à une prothèse de polypropylene ordinaire à poids élevé (Prolene) en ce qui concerne les conséquences fonctionnelles et la réponse morphologiques tissulaires. Après implantation «inlay» de la prothèse chez des rats pendant 3, 21, et 90 jours, la mobilité abdominale a été analysée en trois dimensions par photogrammétrie et on a mesuré la force de rupture entre la zone anastomotique et la prothèse. On a pratiqué un examen histologique des tissus expiantes explorant la réaction histologique eu égard à l’importance de Pinfiltrat inflammatoire, la vascularisation et l’incorporation des tissu adipeux. Le nombre de granulocytes, de macrophages, de fibroblastes, de lymphocytes et de cellules géantes en rapport avec un corps étranger a été évalué pour la qualité de la réponse tissulaire. La réponse cellulaire a été mesurée par le nombre de cassures des filaments d’ADN et le taux d’apoptose (TUNEL), la prolifération (KJ67) et le stress (HSP70) cellulaires. En analysant les résultats, la restriction de la mobilité de la paroi abdominale a été significativement réduite par rapport aux réparations par prothèse à poids élevé: la réaction inflammatoire et la formation de tissu conjonctif ont été très diminuée. L’apoptose et la prolifération cellulaire étaient considérablement plus basses alors que l’expression de la HSP70 cytoprotective a été significativement augmentée. Pour conclure, l’étude présente confirme les bénéfice des modifications de la prothèse. La nouvelle modification de la prothèse, à bas poids (Vypro II), pourrait être intéressante pour la cure de hernie inguinale.ResumenLa operación quirúrgica más frecuente es la herniorrafiahernioplastia inguinal. Junto a las técnicas convencionales con cirugía abierta o laparoscópica, la herniorrafia sin tensión mediante el empleo de prótesis, que refuerzan la pared abdominal, se emplean cada vez mas e incluso, en algunos países, estas son las técnicas utilizadas de forma estándar. Con motivo de los buenos resultados obtenidos en el tratamiento de las eventraciones con mallas estructuradas con escaso material, se ha desarrollado una nueva malla modificada (Vypro II) para la hernioplastia sin tensión de las hernias inguinales. En el presente estudio, se efectúa un estudio comparativo, entre esta nueva malla de bajo peso (Vypro II) compuesta de prolipropileno y poliglactin multifilamentoso y la malla de gran peso, utilizada habitualmente, compuesta por polipropileno (Prolene), por lo que a las respuestas funcionales y morfológicas texturales de ambos implantes se refiere. Tras su implantación “in-lay” en ratas, se estudió a los 3, 21, y 90 días la movilidad de la pared abdominal por medio de un fotográmetro tridimensional, así como la fuerza de tensión en la zona de sutura y en la misma malla; muestras explantadas de tejido se estudiaron histológicamente para valorar la reacción inflamatoria, vascularización y crecimiento, dentro de la malla, de tejido conjuntivo y graso. Para evaluar la calidad de la respuesta textural, se efectuó un recuento del número de granulocitos, macrófagos, fibroblastos, linfocitos y células gigantes a cuerpo extraño. La respuesta celular se trató de valorar midiendo: las soluciones de continuidad del ADN catenario y la apóptosis (TUNEL), la proliferación (Ki67) y agresión celular (HSP70). El análisis de los resultados demuestra que la restricción de la movilidad de la pared abdominal es significativamente menor que la observada utilizando mallas de elevado peso: la reacción inflamatoria y la formación de tejido conjuntivo fue marcadamente menor. La apóptosis y proliferación celular alcanzó niveles muy bajos y la expresión citoprotectora HSP70 aumentó significativamente. En conclusión: el presente estudio confirma el efecto beneficioso por lo que a la reducción de material, que se emplea en la confección de la malla, atañe. La nueva modificación de una malla de bajo peso (Vypro II) tiene muchas ventajas para el tratamiento quirúrgico de las hernias inguinales.

Mesh Implants in Hernia Repair Inflammatory Cell Response in a Rat Model

Background: In the reinforcement of the abdominal wall with mesh implants, various complications including hernia recurrence, abdominal pain, seroma formation and infection are discussed to depend on the biocompatibility of the alloplastic prosthesis. Particularly macrophages, T-cells and mast cells have been shown to play a major role in the inflammatory response to biomaterials. To approach biocompatibility of surgical meshes we therefore examined the infiltrate of these cells as well as the proliferation rate in response to different clinically applied materials. Materials and Methods: Three mesh materials (polypropylene: PP, Prolene®; polyethylene terephthalate: PET, Mersilene®, and polypropylene/polyglactin: PP + PG, Vypro®) were compared after inlay implantation in a standardized rodent animal model. A suture-closed laparotomy served as control. After 7 and 90 days of implantation, histochemical analysis of the inflammatory response to all biomaterials was performed: macrophages (ED3), T-cells (CD3), proliferating cells (PCNA) and mast cells (Giemsa) were investigated. Results: In all groups a persisting T-cell response was observed. Colonization of the interface with macrophages showed a pronounced reduction in the PP + PG-mesh group. Infiltration of mast cells at the tissue graft interface showed a time-dependent decrease in the PET- and PP + PG-mesh groups, whereas in contrast, index of mast cells increased in the PP-mesh group. At both time points, indices of proliferation were highest in the PP-mesh group. Conclusion: The present data confirm the development of a biomaterial-dependent chronic inflammatory response to surgical meshes with macrophages as the predominant cell type. Further research on the recruitment of inflammatory cells and in particular on the role of mast cells and their granular products should be encouraged.

Analysis of collagen-interacting proteins in patients with incisional hernias.

BackgroundIn recent years a disorder of the collagen metabolism has been suggested for the pathogenesis of abdominal wall hernias. Previous investigations of skin specimens revealed a reduction in the collagen I/III ratio and alterations in matrix metalloproteinases in patients with incisional hernias. We investigated known collagen-interacting proteins to further characterize connective tissue in these patients.Patients and methodsSkin scars from patients with either primary or recurrent incisional and recurrent inguinal hernias, as a subgroup of incisional hernias, were analyzed for overall collagen content and for the distribution of collagen types I and III by crosspolarization microscopy. The expression of collagen type V, collagen receptor discoidin domain receptor 2, matrix metalloproteinase 1, connective tissue-like growth factor, and tenascin was determined by immunohistochemistry. Mature abdominal skin scars from patients without evident hernia served as controls.ResultsPatients with recurrent incisional hernia showed lowest ratios of collagen types I to III. Contents of overall collagen and of collagen type V did not differ between the groups. In patients with either primary or recurrent incisional hernias the proportion of collagen receptor discoidin domain receptor 2 positive cells was increased. Matrix metalloproteinase 1 expression was more pronounced in patients with recurrent incisional or inguinal hernias than in controls. Connective tissue-like growth factor was significantly increased in recurrent inguinal hernia patients. The expression of tenascin was notably decreased in all hernia groups.ConclusionsThe observed alterations in the expression of collagen-interacting proteins again indicate the possibility of a fundamental connective tissue disease as the causal factor in the pathogenesis of (recurrent) incisional hernias.

Influence of polyglecaprone 25 (Monocryl) supplementation on the biocompatibility of a polypropylene mesh for hernia repair

Background: Supplementary polyglecaprone 25 (Monocryl) monofilaments were added to a lightweight pure monofilament polypropylene mesh (PP mesh) to improve intraoperative handling (PP+M mesh). This study was designed to evaluate the influence of this additional supplementation on the biocompatibility in a rodent animal model.Methods: Two mesh materials, a composite mesh (PP+M) and the pure polypropylene variant (PP), were compared after subcutaneous implantation in a standardized rat model. Histological analysis of the inflammatory response was performed after 28, 56 and 84 days of implantation. Material absorption, inflammatory tissue reaction, fibrosis and granuloma formation were investigated, as well as the percentage of proliferating and apoptotic cells at the interface.Results: Both mesh materials showed a slight foreign body reaction involving mainly macrophages and foreign body giant cells. Total absorption of the Monocryl filaments of the PP+M mesh occurred between 56 and 84 days of implantation. Both the inflammatory and the fibrotic reaction were decreased (n.s.) in the PP+M mesh group compared to the pure PP mesh. Whereas the percentage of proliferating cells showed no significant difference, the rate of apoptotic cells was significantly decreased in the PP+M mesh group over the whole implantation period.Conclusion: Compared to the pure polypropylene mesh, our data confirm that the use of a polypropylene mesh supplemented with absorbable Monocryl filaments is feasible without additional short-term mesh-related complications in the experimental model or negative side effects on biocompatibility.

A role for the collagen I/III and MMP-1/-13 genes in primary inguinal hernia?

BackgroundAbnormal collagen metabolism is thought to play an important role in the development of primary inguinal hernia. This is underlined by detection of altered collagen metabolism and structural changes of the tissue in patients with primary inguinal hernia. However, it is still unknown whether these alterations reflect a basic dysfunction of the collagen synthesis, or of collagen degradation.MethodsIn the present study, we analysed type I and type III procollagen messenger ribonucleic acid (mRNA) and MMP-1 and MMP-13 mRNA in cultured fibroblasts from the skin of patients with primary inguinal hernia, and from patients without hernia (controls) by reverse transcription polymerase chain reaction (RT-PCR) and Northern Blot.ResultsThe results indicated that the ratio of type I to type III procollagen mRNA was decreased in patients with primary hernia, showing significant differences as compared to controls (p = 0.01). This decrease was mainly due to the increase of type III procollagen mRNA. Furthermore, RT-PCR analysis revealed that the expression of MMP-1 mRNA in patients with primary hernia is equivalent to that of controls (p > 0.05). In addition, MMP-13 mRNA is expressed neither in patients with primary hernia nor in controls.ConclusionWe concluded that abnormal change of type I and type III collagen mRNAs contribute to the development of primary inguinal hernia, whereas the expressions of MMP-1 and MMP-13 mRNA appears not to be involved in the development of primary inguinal hernia. Thus, the knowledge on the transcriptional regulation of collagen in patients with primary inguinal hernia may help to understand the pathogenesis of primary inguinal hernia, and implies new therapeutic strategies for this disease.

Influence of Mesh Materials on Collagen Deposition in a Rat Model

Alterations of the extracellular matrix (ECM) with its major component collagen are increasingly discussed as possible risk factors implicated in the development of abdominal-wall herniation. Because of the widespread use of alloplastic meshes for the surgical repair of hernias, an animal study was performed to analyze the influence of various mesh materials on the quantity and quality of collagen deposition. In 60 male Sprague-Dawley rats an abdominal replacement was performed using three different kinds of mesh materials: polyester (PE), a pure polypropylene (PP), and a composite mesh made of polypropylene and polyglactin (PG). A simple fascia suture repair served as control. The count of fibroblasts, the collagen/protein ratio, the type I/III collagen ratio, and the ex-pression of basic fibroblast growth factor (b-FGF) at the interface were analyzed after 7, 21, and 90 days. The ratio of collagen to overall protein ( w g/mg) showed significant differences comparing different mesh materials (sham controls 38.44 - 16.33 w g/mg, PE 68.5 - 23.8 w g/mg, PP 101.6 - 32.3 w g/mg, PG 49.6 - 11.6 w g/mg at day 90). The ratio of collagen type I/III increased over time in all groups. However, 90 days after mesh implantation the ratio was always significantly lowered compared to the controls. No significant difference was found comparing different mesh materials. The alteration of the scar composition is closely connected to an increased b-FGF expression. b-FGF and count of fibroblasts highly correlated ( r = .95) and showed significant elevated levels compared to simple suture repair. The results of our study strongly support the notion that wound healing is affected by mesh implantation. The quality of the ECM deposition as determined by collagen type I/III ratio is impaired in general, whereas the quantity of ECM deposition is markedly influenced by the kind of mesh material.

Vypro II mesh in hernia repair: impact of polyglactin on long-term incorporation in rats.

Background: To the Vypro II® mesh, a large-pore-sized multifilamentous polypropylene mesh for hernia repair, supplementary polyglactin 910 multifilaments were added to improve intraoperative handling. As it has been suggested that polyglactin induces fibroplastic reactions and wound complications, this study was designed to evaluate the long-term tissue reaction to polyglactin in the Vypro II mesh. Materials and Methods: Two mesh materials, the Vypro II composite mesh (PP + PG) and the pure polypropylene variant (PP), were compared after inlay implantation in a standardized rodent animal model. After 14, 28, 42, 56, 84 and 112 days of implantation, histological analysis of the inflammatory response was performed: material absorption, inflammatory tissue reaction, fibrosis and granuloma formation were investigated. Results: Total absorption of polyglactin filaments of the Vypro II mesh occurred between 56 and 84 days of implantation. Both the inflammatory and the fibrotic reaction were initially increased in the PP + PG mesh group. These differences disappeared in the following implantation period. After 112 days, inflammation was even less pronounced in the PP + PG mesh group. Conclusion: The present data confirm a short-term polyglactin-induced increase in inflammation and fibrosis around implanted Vypro II meshes in rats. With regard to the long-term tissue response, even an anti-inflammatory property of polyglactin multifilaments in low-weight and large-pored polypropylene meshes cannot be ruled out.

Mesh biocompatibility: effects of cellular inflammation and tissue remodelling.

Mesh 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.

Retromuskuläre Netzplastik in Deutschland

ZusammenfassungAusgehend von den enttäuschenden Ergebnissen der primären Nahtreparation von Narbenhernien und neueren Forschungsergebnissen, die eine gestörte Narbenbildung als wesentliche Ursache nahe legen, ist die Netzplastik heute als Methode der Wahl zur Reparation von Narbenhernien anzusehen. Eine konsequente Weiterentwicklung der seit über 40 Jahren eingesetzten Polypropylennetze führte zu den von uns favorisierten großporigen, materialreduzierten Prothesen, die den physiologischen Bedürfnissen der Bauchwand angepasst sind und eine optimale Gewebsintegration sicherstellen. Dabei ließen sich mit der retromuskulären “Sublay-Position” die auch reproduzierbar besten Ergebnisse erzielen. Als wesentlicher Vorteil ist hierbei die Fixierung der Prothese durch den intraabdominellen Druck anzusehen. Im Langzeitverlauf lassen sich hiermit Rezidivraten von unter 10% realisieren. Analysiert man die nach vermeintlich korrekt durchgeführter “Sublay-Reparation” möglichen Rezidivhernien, so ist im Wesentlichen eine inadäquate Überlappung der Prothese meist am kranialen oder kaudalen Ende der Inzision für das Versagen der Operation verantwortlich zu machen. Aus unserer Sicht stellt daher eine Überlappung von mindestens 5–6 cm in allen Richtungen eine zwingend einzuhaltende Voraussetzung für eine erfolgreiche Operation dar. Insbesondere mit den modernen leichtgewichtigen Netzen lassen sich mit der retromuskulären “Sublay-Netzplastik” exzellente Ergebnisse bezüglich Rezidivraten, Komplikationen und Patientenkomfort erzielen.AbstractSince the onset of an incisional hernia is caused by the biological problem of forming stable scar tissue, the mesh techniques are now the methods of choice for incisional hernia repair. Polypropylene is the material most widely used for open mesh repair. New developments have led to low-weight, large-pore polypropylene prostheses, which have been adapted to the physiological requirements of the abdominal wall and permit a reliable tissue integration. These meshes make it possible for a scar net to form rather than a stiff scar plate, thus helping to avoid the complications encountered with the use of earlier meshes. The ideal position for the mesh seems to be the retromuscular underlay position, in which the force of abdominal pressure holds the prosthesis tightly against the deep surface of the muscles. The retromuscular underlay repair technique has yielded the lowest incidence rates for recurrence: around 10% even after long-term follow up. Analysis of the failures after open mesh repair suggests that inadequate size of the mesh with insufficient overlap at the edges is the main reason for recurrence. An overlap of at least 5–6 cm all round must therefore be considered mandatory for successful reinforcement of the abdominal wall. Open mesh repair, particularly with modern low-weight polypropylene meshes applied by the retromuscular underlay technique, offers excellent results in the treatment of incision hernias, even in long-term follow-up studies.

The rare epidemiologic coincidence of diverticular disease and advanced colonic neoplasia

Background and aimsIn Western industrialised countries the prevalence of neoplastic colonic lesions and diverticular disease markedly increases with age. In contrast, the coincident occurrence of both diseases seems to fall below their individual epidemiologic estimates. Because directly comparing data are rare, this retrospective study evaluates the coincidence of neoplastic lesions and diverticular disease.Patient and methodsA total of 1,838 patients from 1986 to 2000 were admitted to the study. For 1,326 patients—56% male (n=741), 44% female (n=585), mean age 64 (±11.83 SD)—with a resection due to colonic cancer, the documented findings of colonoscopy, colonic contrast enema, and/or histopathology were analysed with regard to the prevalence of colonic diverticulosis. In 512 patients—51% male (n=263), 49% female (n=249), mean age 60 (±12.59 SD)—with a colonic resection due to diverticulitis, the synchronous or metachronous occurrence of neoplastic colonic lesions was recorded using the database of the Tumour Centre, Aachen. To compare the observed results with published epidemiology, statistical analysis included age-referred binomial tests and an age-stratified analysis (Cochran–Mantel–Haenszel test). Odds ratios (OR) were also calculated. P<0.05 was considered to indicate locally statistical significance.ResultsIn the cancer group, we found a statistically significant reduced rate of diverticula in nearly all age categories and the age-stratified analyses (corresponding OR 0.30–0.51). Consistently, the diverticulitis group revealed a statistically significant decreased rate of advanced colonic neoplastic lesion in nearly all age categories and all age-stratified analyses (corresponding OR 0.13–0.43).ConclusionOur results indicate that patients with colonic neoplastic lesions or diverticular disease probably form heterogeneous groups. Because current results from molecular biology emphasize the impact of the extracellular matrix on the genesis of diverticulosis and colonic cancer, the observed heterogeneity could be an expression of a distinct composition of the local milieu.