Bernd Klosterhalfen

Foreign Body Reaction to Meshes Used for the Repair of Abdominal Wall Hernias

OBJECTIVE To investigate the local tissue reactions to meshes that had been removed from humans. DESIGN Open study SETTING Surgical department of the technical University, Aachen, Germany. MATERIAL Samples of 17 non-absorbable meshes (1 polyester, 10 polypropylene, 2 reduced polypropylene, and 4 polytetrafluorethylene, PTFE) and 1 absorbable mesh (polyglactin 910) that had been implanted for repair of abdominal wall defects. INTERVENTIONS Light and transmission electron microscopy, immunohistochemistry, and histological examination. MAIN OUTCOME MEASURES Signs of inflammatory response. RESULTS Light microscopy showed chronic inflammatory tissue reaction, even after years, with pronounced differences among materials. Partial volume of inflammatory cells (%) varied from 32 in polypropylene, to 12 in expanded PTFE, 8 in polyester, and 7 in reduced polypropylene. Formation of connective tissue correlated significantly with the extent of the inflammatory reaction (p<0.01). In meshes implanted for long periods there were still numerous macrophages at the interface between tissue and polypropylene (45%), polyester (45%), expanded PTFE (25%), and reduced polypropylene (22%). There was no difference in time dependent tissue reactions (p = 0.19). CONCLUSION Inflammation around alloplastic materials used to repair defects in the abdominal wall persists for many years. There was evidence of long term wound complications as a result of persistent foreign body reactions. Further studies are required to evaluate the long term tissue response to these materials.

The lightweight and large porous mesh concept for hernia repair

In modern hernia surgery, there are two competing mesh concepts which often lead to controversial discussions, on the one hand the heavyweight small porous model and on the other, the lightweight large porous hypothesis. The present review illustrates the rationale of both mesh concepts and compares experimental data with the first clinical data available. In summary, the lightweight large porous mesh philosophy takes into consideration all of the recent data regarding physiology and mechanics of the abdominal wall and inguinal region. Furthermore, the new mesh concept reveals an optimized foreign body reaction based on reduced amounts of mesh material and, in particular, a significantly decreased surface area in contact with the recipient host tissues by the large porous model. Finally, recent data demonstrate that alterations in the extracellular matrix of hernia patients play a crucial role in the development of hernia recurrence. In particular, long-term recurrences months or years after surgery and implantation of mesh can be explained by the extracellular matrix hypothesis. However, if the altered extracellular matrix proves to be the weak area, the decisive question is whether the amount of material as well as mechanical and tensile strength of the surgical mesh are really of significant importance for the development of recurrent hernia. All experimental evidence and first clinical data indicate the superiority of the lightweight large porous mesh concept with regard to a reduced number of long-term complications and particularly, increased comfort and quality of life after hernia repair.

Modified mesh for Hernia repair that is adapted to the physiology of the abdominal wall

OBJECTIVE To develop a new mesh for hernia repair that is adapted to the physiological forces. DESIGN Animal experiment. SETTING Surgical Department of the RWTH-Aachen. ANIMALS Wistar rats MAIN OUTCOME MEASURES Textile analysis, tensile strength, bending stiffness, histology and morphometry. RESULTS After textile analysis of commercially available meshes in clinical use we defined the physiological forces and constructed a new mesh (Soft Hernia Mesh, SHM) based on a combination of non-absorbable polypropylene and absorbable polyglactin 910. The amount of non-absorbable material could be reduced to < 30% compared with Marlex while still guaranteeing the necessary pulling force of 16 N/cm. Improvements of the hosiery structure improved the symmetrical distribution of the retaining forces in all directions. Compared with the considerable restriction of the abdominal wall mobility by Prolene (polypropylene) and Mersilene (polyester) meshes there was no increase in the bending stiffness after the implantation of the new mesh. Histological examination showed a pronounced reduction of the inflammatory reaction in the tissues, and the collagen bundles were orientated merely around the mesh filaments instead of forming a scar plate that completely embedded the mesh. CONCLUSION Different meshes caused specific histological reactions with changes of their mechanical properties after implantation in rodents. A new mesh with a reduced amount of polypropylene showed both less inflammation and less restriction in the mobility of the abdominal wall though it exceeded the required tensile strength of 16 N/cm.

Shrinking of Polypropylene Mesh in vivo: An Experimental Study in Dogs

OBJECTIVE To assess the extent of shrinkage of meshes used for hernia repair. DESIGN Experimental study in dogs. SETTING University hospital, Germany and University Research Centre, Moscow. ANIMALS 10 dogs had monofilament polypropylene meshes that weighed 95 g/m2 (Marlex) or multifilament reduced polypropylene meshes combined with polyglactin 910 that weighed 55 g/m2 (Soft Hernia Mesh) implanted for either 3 or 6 months. MAIN OUTCOME MEASURES Histological appearance and radiological assessment of the position and area of the mesh. RESULTS After 4 weeks the area of mesh in the monofilament group was reduced from to 139 (11) to 75 (8) cm2 (54%) and that of the multifilament from 116 (18) to 77 (20) cm2 (66%). The multifilament mesh with the reduced amount of polypropylene showed less inflammatory response and less shrinkage. The mesh did not seem to have moved. CONCLUSION Meshes that contain a lot of polypropylene shrink to about 30%-50% of their original size after 4 weeks, requiring an overlap of at least 3 cm if implanted subfascially. Reduction in the polypropylene content decreases both the inflammatory response and the shrinkage. Meshes with big pores are less likely to fold and improve compatibility.

Functional and morphological evaluation of different polypropylene-mesh modifications for abdominal wall repair.

Modern surgical hernia repair depends increasingly on synthetic meshes for the reconstruction of the abdominal wall. Despite the undisputed advantages of the polypropylene (PP) meshes currently available (Marlex, Prolene), reports of complications after implantation are increasing. Although, serious complications such as perforation and fistula formation are rare, minor and local complaints such as seromas, misfeelings and a decreased abdominal wall mobility are observed in about one-half of the patients. In regard to the exaggerated strength of the currently available mesh modifications a reduction of the material should improve the integration of the meshes into the artificial abdominal wall. In the present study, the commercially available basic mesh Prolene has been compared to two newly constructed PP-mesh modifications with reduced amounts of PP. The modifications have gradually been adopted to the physiological requirements of abdominal wall stability and mobility by reducing the amount of PP to 64% (E-BLUE) and 24% (variant A) of the Prolene mesh (developed by ETHICON, Norderstedt, Germany). All PP-mesh variants have been implanted in a rat model and studied by 3D-photogrammetry, tensiometry, light- and electron microscopy, as well as morphometry over implantation intervals of 3, 7, 14, 21 and 90 days. The data show that current constructions of PP-meshes are oversized and definitely restrict abdominal wall mobility in the present model. Sufficient stability of the artificial abdominal wall is even guaranteed by PP-mesh modifications with a reduction of PP-quantity to about 25% of the Prolene mesh. The degree of fibrosis directly correlated with abdominal wall restriction, whereas the formation of connective tissue in the interface PP-fibre/host-issue depends on the amount and activity of the inflammatory reaction. The quantity and quality of inflammation, again, directly relies to the amount of PP and to the surface area in contact with the recipient tissues. Altogether, the present study suggests that a modification of the PP-meshes could be helpful to prevent major and minor complications of surgical PP-meshes.

Topography of the inferior rectal artery: A possible cause of chronic, primary anal fissure

The authors believed that it might be possible to explain the local frequency of the anal fissure at the posterior commissure by an anatomic relationship, and examined the blood supply of the anus. The inferior rectal artery is demonstrated by postmortem angiography and by manual preparations (N=4) and histologic study after angiography of the vessels (N=10). The blood supply at the different sites of the anal canal are demonstrated by a morphometric study (N=20). The inferior rectal artery presents two variants in the postmortem angiographies, type 1 (85. 4 percent) and type 2 (14.6 percent). In type 1, the posterior commissure is less perfused than the other sections of the anal canal. In addition, the blood supply may be more compromised by contusion of the vessels passing vertically through the muscle fibers of the sphincter ani internus muscle during increased sphincter tone. The role of topography in the pathogenesis of the primary anal fissure is illustrated in a model

Expression of cyclooxygenase 2 is an independent prognostic factor in human ovarian carcinoma

Cyclooxygenase-2 (COX-2) is the rate-limiting enzyme in prostanoid biosynthesis and is involved in tumor progression. We investigated expression of COX-1 and COX-2 in cell lines and tumors from ovarian carcinomas. Expression of COX-2 mRNA and protein was detectable in three of five ovarian carcinoma cell lines and was inducible by interleukin-1beta or phorbolester in a subset of cell lines. Prostaglandin E(2) (PGE(2)) production could be inhibited by the selective COX-2 inhibitor NS-398. In malignant ascites of ovarian carcinomas significantly increased levels of PGE(2) were found compared to other carcinomas or nonmalignant ascites (P = 0.03). We investigated expression of COX-2 by immunohistochemistry in 117 ovarian surface epithelial tumors. Expression of COX-2 was detected in 42% of 86 ovarian carcinomas and in 37% of 19 low malignant potential tumors, but not in 12 cystadenomas or 2 normal ovaries. Expression of COX-1 was detected by immunohistochemistry in 75% of 75 invasive ovarian carcinomas and in 75% of 16 low malignant potential tumors, whereas 2 samples from normal ovaries and 8 cystadenomas were positive for COX-1. In univariate survival analysis of invasive carcinomas, expression of COX-2 was associated with a significantly reduced median survival time (log rank test, P = 0.04). For patients younger than 60 years of age, this association was even more significant (P < 0.004). In contrast, expression of COX-1 was no prognostic parameter (P = 0.89). There was no significant correlation between COX-2 or COX-1 expression and other clinicopathological markers. In multivariate analysis expression of COX-2 was an independent prognostic factor for poor survival (relative risk, 2.74; 95% CI, 1.38 to 5.47). Our data indicate that COX-2 expression is an independent prognostic factor in ovarian carcinoma. Based on the results of this study, it would be interesting to investigate whether ovarian carcinoma patients with tumors positive for COX-2 would benefit from treatment with selective COX-2 inhibitors.

PVDF as a new polymer for the construction of surgical meshes

Abdominal hernia repair is the most frequently performed operation in surgery. Mostly due to lowered recurrence rates mesh repairs in hernia surgery have become an integral component despite increasing mesh-related complications. Current available mesh prosthesis are made of polypropylene (PP). polyethylene-terephtalat or polytetrafluorethylene. though all of them reveal some disadvantages. The introduction of new materials seems to be advisable. Caused by supposed advantageous textile properties and tissue response two mesh modifications made of polyvinylidene fluoride (PVDF) for abdominal hernia repair were developed. In the present study the PVDF meshes were compared to a common heavy weight PP-mesh (Prolene) in regard to functional consequences and morphological tissue response. After implantation in rats as inlay for 3, 14, 21, 42 and 90 days abdominal wall mobility was recorded by three-dimensional photogrammetry. Tensile strength of the suture zone and the mesh itself were determined. Explanted tissue samples have been investigated for their histological reaction in regard to the inflammatory infiltrate. vascularisation, connective and fat tissue ingrowth. Number of granulocytes, macrophages, fibroblasts, lymphocytes and foreign giant body cells have been evaluated to reflect quality of tissue response. The cellular response was grasped by measurement of DNA strand breaks and apoptosis (TUNEL), proliferation (Ki67) and cell stress (HSP70). Analyzing the results confirmed that construction of hernia meshes made of PVDF could be an advantageous alternative to the commonly used materials due to an improved biostability. lowered bending stiffness and a minimum tissue response.

Abnormal collagen I to III distribution in the skin of patients with incisional hernia.

The surgical mesh-free repair of incisional hernias has to face recurrence rates of up to 50%. Apart from technical faults this is probably due to collagen metabolic disorders, known to play an important role in the development of inguinal hernia. In particular an altered ratio of collagen types I and III with an increase in collagen type III has been claimed to reduce the mechanical strength of connective tissues. Therefore, we investigated the content of collagen types I and III in the skin of patients with incisional hernia (n = 7) and recurrent incisional hernia (n = 5) in comparison to controls with healthy skin (n = 7) and normal skin scar (n = 7) both by immunohistochemistry and Western blot analysis. Both immunohistochemistry and Western blot analysis revealed a decrease in the ratio of collagen I/III due to a concomitant increase in collagen III. The patients with incisional hernias and with recurrent incisional hernias showed a ratio of 1.0 ± 0.1 and 0.8 ± 0.1, respectively, whereas the controls exhibit a ratio of 2.1 ± 0.2 in healthy skin and of 1.2 ± 0.2 in normal skin scar, respectively. The decrease was highly significant (p < 0.01) between the patients with either primary or recurrent hernia and the controls or the normal scar, as well as between controls and normal scar, whereas there was not any significant difference between primary and recurrent hernia (p > 0.05). Our data for the first time confirmed that the presence of incisional hernia is accompanied by impaired collagen synthesis in the skin. The decreased tensile strength of collagen type III may play a key role in the development of incisional hernias. Furthermore, it might explain the high recurrence rates of hernia repair by simple closure, as a repetition of the primarily failing technique, and the improvement by the additional use of alloplastic material.

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.