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Cirrhotic patients often suffer from cirrhotic cardiomyopathy (CCM). Previous animal models of CCM were inconsistent concerning the time and mechanism of injury; thus, the temporal dynamics and cardiac vulnerability were studied in more detail. Rats underwent bile duct ligation (BDL) and a second surgery 28 days later. Cardiac function was assessed by conductance catheter and echocardiography. Histology, gene expression, and serum parameters were analyzed. A chronotropic incompetence (Pd31 < 0.001) and impaired contractility at rest and a reduced contractile reserve (Pd31 = 0.03, Pdob-d31 < 0.001) were seen 31 days after BDL with increased creatine (Pd35, Pd42, and Pd56 < 0.05) and transaminases (Pd31 < 0.001). A total of 56 days after BDL, myocardial fibrosis was seen (Pd56 < 0.001) accompanied by macrophage infiltration (CD68: Pgroup < 0.001) and systemic inflammation (TNFα: Pgroup < 0.001, white blood cell count: Pgroup < 0.001). Myocardial expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) was increased after 31 (Pd31 < 0.001) and decreased after 42 (Pd42 < 0.001) and 56 days (Pd56 < 0.001). Caspase-3 expression was increased 31 and 56 days after BDL (Pd31 = 0.005; Pd56 = 0.005). Structural changes in the myocardium were seen after 8 weeks. After the second surgery (second hit), transient myocardial insufficiency with secondary organ dysfunction was seen, characterized by reduced contractility and contractile reserve.

Journal of biomedical materials research / A (2022). doi:10.1002/jbm.a.37494, Published by Wiley, New York, NY [u.a.]

International journal of molecular sciences 23(22), 13806 (2022). doi:10.3390/ijms232213806 special issue: "Special Issue "Molecular Frontiers in Transplantation-Induced Ischemia Reperfusion Injury" / Special Issue Editor: Dr. Raphaël Thuillier, Guest Editor", Published by Molecular Diversity Preservation International, Basel

Cancers 14(9), 2190 (2022). doi:10.3390/cancers14092190 special issue: "Special Issue "Perihilar Cholangiocarcinoma" / Special Issue Editors: Dr. Bas Groot Koerkamp, Guest Editor; Dr. Stefan Büttner, Guest Editor; Dr. Pim B. Olthof, Guest Editor", Published by MDPI, Basel

Aim Polypropylene (PP) mesh is widely used to reinforce tissues. The foreign body reaction (FBR) to the implant is dominated by innate immune cells, especially macrophages. However, considerable numbers of adaptive immune cells have also been regularly observed, which appear to play a crucial role in the long-term host response. This study investigated the FBR to seven human PP meshes, which were removed from the abdomen for recurrence after a median of one year. Material and Methods Using immunofluorescence microscopy and distance maps, the FBR was spatially analyzed for various innate (e.g., CD68+ macrophages, CD56+ NK) and adaptive immune cells (CD3+ T, CD4+ T-helper, CD8+ cytotoxic, FoxP3+ T-regulatory, CD20+ B) as well as “conventional” immune cells (defined as cells expressing their specific immune cell marker without co-expressing CD68). Results T-helper cells (19%) and regulatory T-cells (25%) were present at comparable rates to macrophages, and clustered significantly toward the mesh fibers. For all cell types the lowest proportions of “conventional” cells (< 60%) were observed at the mesh–tissue interface, but increased considerably at about 50–100 µm, indicating reduced stimulation with rising distance to the mesh fibers. Conclusions Both innate and adaptive immune cells participate in the chronic FBR to PP meshes with T cells and macrophages being the predominant cell types, respectively. Furthermore, many cells present a “hybrid” pattern near the mesh fibers. The complexity of the local immune reaction may explain why approaches focusing on specific cell types have not been very successful in reducing the chronic FBR.

The impact of aspirin use after the diagnosis of colorectal cancer is unknown. Among others, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) mutational status was proposed as a molecular biomarker for the response to adjuvant aspirin therapy. However, prognostic data on aspirin use after a colorectal cancer diagnosis in relation to KRAS mutational status is limited. In a single-center retrospective study, we obtained KRAS and PIK3CA mutational status in a cohort of 153 patients with a first diagnosis of colorectal cancer receiving tumor surgery with curative intent. PIK3CA mutational status was determined by pyrosequencing, and KRAS mutational status was determined by next-generation sequencing. Clinicopathological data and survival data were assessed using patient records and reporting registers. We observed a significant 10-year overall survival benefit in patients with aspirin use and combined wild-type PIK3CA and mutated-KRAS tumors (HR = 0.38, 95% CI = 0.17–0.87, p = 0.02), but not in patients without aspirin use. Our data indicate a benefit of aspirin usage particularly for patients with combined wild-type PIK3CA and mutated-KRAS tumor characteristics.

Background The current standard for open and laparoscopic repair of incisional hernia consist of an abdominal wall augmentation by mesh implantation. However, the ideal fixation method of the prothesis material remains under discussion, due to potential complications of conventional fixation methods such as chronic abdominal pain or intestinal obstruction. As the use of adhesive based mesh fixation is an option of growing interest, the aim of this experimental study was to investigate the strength and biocompatibility of two newly developed polyurethane-based adhesives in comparison to a cyanoacrylatic adhesive, which is currently in clinical use. Methods Two experimental polyurethane/urea-based adhesives (Adhesive-A and Adhesive-B) were compared to a conventional cyanoacrylatic adhesive and an untreated control group. Biomechanical testing was carried out using a pull-out test in uniaxial tensile mode, while biocompatibility assessment was performed in a rat model with 40 Sprague-Dawley rats receiving a subcutaneous implanted PVDF mesh fixed by the corresponding adhesive. Histological and immunohistochemical analysis by a Tissue FAXS system examined the tissue integration of the mesh/adhesive combination and characterized the foreign body reaction. Results Biomechanical testing of the mesh/adhesive combinations showed a minimal strength of 15.08 N without a significant difference between the groups. Cellular penetration into the mesh/adhesive interface was significantly improved after application of polyurethane adhesives and Adhesive-A showed a significantly lower migration of CD68 positive cells to the adhesive sites compared to cyanoacrylate after 7 days. Conclusion The developed polyurethane-based adhesives are a promising alternative with sufficient adhesive strength and superior short-term biocompatibility to cyanoacrylate.

Seit Mitte der 90er Jahre stutzt sich die operative Versorgung der Leistenhernie vornehmlich auf die Verstarkung der Leistenregion durch Implantation von die Bruchlucke weit uberlappenden, grosflachigen, textilen Netzen oder alternativ durch direkten Verschluss der Bruchlucken mittels Kunststoff-Plugs. Wahrend bei den flachen Netzen bereits die Integration in Narbe oder in lokales Gewebe die Fixation des idealerweise spannungsfrei eingebrachten Implantates gewahrleistet, erfordert der Plug-Stopfen eine suffiziente Narbenfixation in der Bruchlucke zur Pravention einer Migration bei lokaler mechanischer Belastung. Angesichts der gestorten Narbenbildung mit Ausbildung minderwertigen Kollagens bei vielen Hernienpatienten erscheint es nicht uberraschend, dass im Vergleich zu flachen Netzen der Plug-Verschluss mit erhohten Rezidivraten bzw. Migrationsraten behaftet ist.

PLOS ONE 16(8), e0256790 (2021). doi:10.1371/journal.pone.0256790, Published by PLOS, San Francisco, California, US

Hernia : the journal of hernias and abdominal wall surgery 26(1), 309-323 (2022). doi:10.1007/s10029-021-02396-7, Published by Springer, Paris

Background Currently, the lack of consensus on postoperative mesh-tissue adhesion scoring leads to incomparable scientific results. The aim of this study was to develop an adhesion score recognized by experts in the field of hernia surgery. Methods Authors of three or more previously published articles on both mesh-tissue adhesion scores and postoperative adhesions were marked as experts. They were queried on seven items using a modified Delphi method. The items concerned the utility of adhesion scoring models, the appropriateness of macroscopic and microscopic variables, the range and use of composite scores or subscores, adhesion-related complications and follow-up length. This study comprised two questionnaire-based rounds and one consensus meeting. Results The first round was completed by 23 experts (82%), the second round by 18 experts (64%). Of those 18 experts, ten were able to participate in the final consensus meeting and all approved the final proposal. From a total of 158 items, consensus was reached on 90 items. The amount of mesh surface covered with adhesions, tenacity and thickness of adhesions and organ involvement was concluded to be a minimal set of variables to be communicated separately in each future study on mesh adhesions. Conclusion The MEsh Tissue Adhesion scoring system is the first consensus-based scoring system with a wide backing of renowned experts and can be used to assess mesh-related adhesions. By including this minimal set of variables in future research interstudy comparability and objectivity can be increased and eventually linked to clinically relevant outcomes.

Background The incidence of incisional hernia is with up to 30% one of the frequent long-term complication after laparotomy. After establishing minimal invasive operations, the laparoscopic intraperitoneal onlay mesh technique (lap. IPOM) was first described in 1993. Little is known about the foreign body reaction of IPOM-meshes, which covered a defect of the parietal peritoneum. This is becoming more important, since IPOM procedure with peritoneal-sac resection and hernia port closing (IPOM plus) is more frequently used. Methods In 18 female minipigs, two out of three Polyvinylidene-fluoride (PVDF) -meshes (I: standard IPOM; II: IPOM with modified structure [bigger pores]; III: IPOM with the same structure as IPOM II + degradable hydrogel-coating) were placed in a laparoscopic IPOM procedure. Before mesh placement, a 2x2cm peritoneal defect was created. After 30 days, animals were euthanized, adhesions were evaluated by re-laparoscopy and mesh samples were explanted for histological and immunohistochemichal investigations. Results All animals recovered after implantation and had no complications during the follow-up period. Analysing foreign body reaction, the IPOM II mesh had a significant smaller inner granuloma, compared to the other meshes (IPOM II: 8.4 µm ± 1.3 vs. IPOM I 9.1 µm ± 1.3, p Conclusion A peritoneal defect covered by IPOM prostheses leads to an increased foreign body reaction compared to intact peritoneum. Whenever feasible, a peritoneal defect should be closed accurately before placing an IPOM-mesh to avoid an excessive foreign body reaction and therefore inferior biomaterial properties of the prosthesis.

Background Mesh implants are widely used to reinforce the abdominal wall, although the inevitable inflammatory foreign body reaction (FBR) at the interface leads to complications. Macrophages are suspected to regulate the subsequent scar formation, but it is still unclear whether adequate fibrous scar formation with collagen deposition depends mainly on the presence of M1 or M2 macrophages. Methods This study investigated the FBR to seven human polypropylene meshes, which were removed after a median incorporation time of 1 year due to the primary complaint of recurrence. Using immunofluorescence, the FBR was examined in six regional zones with increasing distance from the mesh fibers up to 350 µm, based on the cell densities, macrophage M1 (CD86) and M2 (CD163, CD206) phenotypes, deposition of collagen-I and -III, and expression of matrix metalloproteinase-2 (MMP-2) and -8 as indicator of collagen degradation. Results All mesh–tissue complexes demonstrated a decrease in cell density and macrophages with distance to the mesh fibers. Overall, about 60% of the macrophages presented an M2 phenotype, whereas only 6% an M1 phenotype. Over 70% of macrophages showed co-expression with collagen-I or -III and over 50% with MMP-2. Conclusions The chronic FBR to polypropylene meshes is associated with an M2 macrophage response, which is accompanied by collagen deposition and MMP-2 expression. These findings challenge the idea that mainly M1 macrophages are related to inflammation and highlights that iatrogenic attempts to polarize these cells towards the M2 phenotype may not be a solution to ameliorate the long-term foreign body reaction.

Today the use of textile meshes has become a standard for the treatment of abdominal wall hernias and for the reinforcement of any tissue repair as the strength of the implant decreases the recurrence rates. With increasing use, side effects of the textile implants became apparent, as well.Based on publications in Medline over the past decade, general and specific benefits, as well as risks, are discussed with the challenge to define individual risk-benefit ratios. For meshes, certain high-risk or low-risk conditions can be defined. In an attempt to eliminate mesh-related risks, quality control for medical devices has meanwhile been revised. In both the USA and the EU post-market surveillance studies are required to keep medical devices approved.The impact of material on the complication rate will vary depending on the patient's co-morbidity or the risks of the procedure. Even the best material can end up with disappointing results in case of poor healing or poor surgery. On the other hand, when using high-risk devices, most of the complications after excellent surgery with excellent indication can be supposed to be mesh-related. Thus, the use of low-risk devices is recommended even though its advantage may not be demonstrable in clinical studies.

Background: The open abdomen with mesh implantation, followed by early reoperation with fascial closure, is a modern surgical approach in difficult clinical situations such as severe abdominal sepsis. As early fascial closure is not possible in many cases, mesh-mediated fascial traction is helpful for conditioning of a minimized ventral hernia after open abdomen. The aim of this study was to evaluate the clinical utilization of an innovative elastic thermoplastic polyurethane mesh (TPU) as an abdominal wall inlay in a minipig model. Methods: Ten minipigs were divided in two groups, either receiving an elastic TPU mesh or a nonelastic polyvinylidene fluoride (PVDF) mesh in inlay position of the abdominal wall. After 8 weeks, mesh expansion and abdominal wall defect size were measured. Finally, pigs were euthanized and abdominal walls were explanted for histological and immunohistochemical assessment. Results: Eight weeks after abdominal wall replacement, transversal diameter of the fascial defect in the TPU group was significantly smaller than in the PVDF group (4.5 cm vs. 7.4 cm; p = 0.047). Immunhistochemical analysis showed increased Ki67 positive cells (p = 0.003) and a higher number of apoptotic cells (p = 0.047) after abdominal wall replacement with a TPU mesh. Collagen type I/III ratio was increased in the PVDF group (p = 0.011). Conclusion: Implantation of an elastic TPU mesh as abdominal wall inlay is a promising approach to reduce the size of the ventral hernia after open abdomen by mesh-mediated traction. However, this effect was associated with a slightly increased foreign body reaction in comparison to the nonelastic PVDF.

Background: Abdominal adhesions are one of the most common complications after abdominal surgery, and fibrin is suspected to be a crucial component. The aim of the current study was an in vivo evaluation of a new recombinant fibrinogenase (AK03) in two animal models.Methods: Sixty-four rats were randomly divided into four groups (sodium chloride [NaCl], icodextrin, AK03 low dose, and AK03 high dose) and evaluated at two time endpoints. Adhesion model comprised both a visceral defect (terminal ileum) and parietal defect. Test (AK03) and control substances (NaCl and icodextrin) were administered intraperitoneally after setting the intraabdominal defects. A second dose was administered 24 h after surgery. Plasma fibrinogen values were taken at baseline and after 7 and 21 d, respectively. Rats were sacrificed after 7 or 21 d for macroscopic (Diamond score) and immunohistochemical investigations.Results: After 7 and 21 d, the Diamond score of postsurgical adhesions were significantly lower in both AK03-treated groups compared with NaCl control group (P = 0.02). There were no unspecific systemic side effects in both treatment groups and no decrease in plasma fibrinogen concentration. In none of the four groups was there any evidence for impaired wound repair. Microscopically in the area of the parietal defect, we saw less cluster of differentiation 3(+) T-lymphocytes and cluster of differentiation 68(+) macrophages in both groups receiving AK03 compared with the NaCl and icodextrin control groups.Conclusions: The results of this study indicate that the new recombinant fibrinogenase AK03 effectively prevents peritoneal adhesions without causing side effects, notably systemic fibrinogen depletion, bleeding, or impaired wound repair. Due to these results, future clinical studies may be promising. (C) 2017 Elsevier Inc. All rights reserved.

Background: The frequency of laparoscopic approaches increased in hernia surgery over the past years. After mesh placement in IPOM position, the real extent of the meshes configurational changes after termination of pneumoperitoneum is still largely unknown. To prevent a later mesh folding it might be useful to place the mesh while it is kept under tension. Conventionally used meshes may lose their Effective Porosity under these conditions due to poor elastic properties. The aim of this study was to evaluate a newly developed elastic thermoplastic polyurethane (TPU) containing mesh that retains its Effective Porosity under mechanical strain in IPOM position in a porcine model. It was visualized under pneumoperitoneum using MRI in comparison to polyvinylidenefluoride (PVDF) meshes with similar structure. Methods: In each of ten minipigs, a mesh (TPU containing or native PVDF, 10 x 20cm) was randomly placed in IPOM position at the center of the abdominal wall. After 8weeks, six pigs underwent MRI evaluation with and without pneumoperitoneum to assess the visibility and elasticity of the mesh. Finally, pigs were euthanized and abdominal walls were explanted for histological and immunohistochemical assessment. The degree of adhesion formation was documented. Results: Laparoscopic implantation of elastic TPU meshes in IPOM position was feasible and safe in a minipig model. Mesh position could be precisely visualized and assessed with and without pneumoperitoneum using MRI after 8weeks. Elastic TPU meshes showed a significantly higher surface increase under pneumoperitoneum in comparison to PVDF. Immunohistochemically, the amount of CD45-positive cells was significantly lower and the Collagen I/III ratio was significantly higher in TPU meshes after 8weeks. There were no differences regarding adhesion formation between study groups. Conclusions: The TPU mesh preserves its elastic properties in IPOM position in a porcine model after 8weeks. Immunohistochemistry indicates superior biocompatibility regarding CD45-positive cells and Collagen I/III ratio in comparison to PVDF meshes with a similar structure.

Introduction Most aspects of implant-assisted reconstruction of pelvic floor in males and females are under debate and the research is not standardized. Registries are supposed to shed light to the indications, surgical techniques and material properties and to establish a standardized evaluation. Methods A working group was formed to create an online platform for registration and outcome measurement of implant-assisted operations for pelvic organ prolapse (POP) and female and male stress urinary incontinence (SUI). 20 patients with modified mesh materials were evaluated over 23 months follow up in the registry to prove the feasibility of the registry. For validation a previously published modified "satisfaction, anatomy, continence, safety – S.(A.)C.S score" was used. Results A consensus was met on definitions and classifications of patient variables, surgical procedures and implants, as well as outcome parameters (efficacy, continence, satisfaction, complications). Different subgroup modules were formed in accordance with treated condition. The maximum score of cure was reached by 25–100% of patients depending on the indication. Conclusion A prospective registry in accordance with IDEAL-D framework is justified for the evaluation and regulation of implants for pelvic floor reconstruction.

The usual approach in hernia surgery is to select the ideal repair method independent of the patient’s characteristics. In the present study, we change the approach to ask which technique is best for the individual patient`s risk profile. For this, two criteria are important: does the patient need reconstruction of the abdominal wall? or does he or she need treatment of symptoms without being exposed to unnecessarily high perioperative risks? In a heuristic selection procedure, 486 consecutive patients were classified according to their characteristics as low-risk or high-risk for postoperative complications. Low-risk patients preferentially underwent open abdominal wall reconstruction with mesh (MFR + mesh), high-risk patients mainly a bridging-mesh procedure, either by laparoscopic (Lap.-IPOM) or open approach (Open-IPOM). Primary outcome was the incidence of postoperative complications. Secondary outcome was the recurrence-free interval. The propensity score was used for covariate adjustment analyzing recurrence rate as well as postoperative complications using Cox regression and logistic regression, respectively. Comparison of all surgical procedures showed risk factors had no independent influence on occurrence of complications (p = 0.110). Hernial gap width was an independent factor for occurrence of complications (p = 0.002). Propensity score adjustment revealed Lap.-IPOM to have a significantly higher recurrence rate than MFR + mesh (HR 2.367, 95% CI 1.123–4.957, p = 0.024). Three or more risk factors were protective against recurrence (HR 0.454, 95% CI 0.221–0.924, p = 0.030). In the univariate Cox regression analysis for recurrence, age >50 years was a protective prognostic factor (HR 0.412, 95% CI 0.245–0.702, p = 0.002). The classification criteria applied were internally validated. The heuristic algorithm ensured that patients at high-risk of complications did not have a higher perioperative complication rate than patients at low-risk.

Implants like meshes for the reinforcement of tissues implement the formation of a persistent inflammation with an ambient fibrotic reaction. In the inflammatory infiltrate several distinct cell types have been identified, but CD68+ macrophages are supposed to be most important. To investigate the collaboration among the various cell types within the infiltrate we performed at explanted meshes from humans double fluorescence staining with CD68 as a constant marker and a variety of other antibodies as the second marker. The list of second markers includes lymphocytes (CD3, CD4, CD8, CD16, CD56, FoxP3, and CD11b) stem cells (CD34), leucocytes (CD45, CD15), macrophages (CD86, CD105, CD163, and CD206); deposition of EC matrix (collagen‐I, collagen‐III, MMP2, and MMP8); Ki67 as a marker for proliferation; and the tyrosine‐protein kinase receptor AXL. The present study demonstrates within the inflammatory infiltrate the abundant capability of CD68+ cells to co‐express a huge variety of other markers, including those of lymphocytes, varying between 5 and 83% of investigated cells. The observation of co‐staining was not restricted to a specific polymer but was seen with polypropylene fibers as well as with fibers made of polyvinylidene fluoride, although with differences in co‐expression rates. The persisting variability of these cells without the functional reduction toward differentiated mature cell types may favor the lack of healing at the interface of meshes.

Parastomal herniation is a frequent complication in colorectal surgery, occurring with a prevalence of 30-80%. The aim of the study was to create a new intraperitoneal colostoma mesh prosthesis (IPST) with enhanced elastic properties made with thermoplastic polyurethane (TPU) monofilaments. We performed open terminal sigmoid colostomies reinforced with either a 10 cm by 10 cm polyvinylidene fluoride (PVDF) or a new TPU/PVDF composite mesh in a total of 10 minipigs. Colostoma was placed paramedian in the left lower abdomen and IPST meshes were fixed intraperitoneal. After 8 weeks, the animals were euthanized after laparoscopic exploration and specimen were explanted for histological investigations. Implantation of a new IPST-mesh with enhanced elastic properties was feasible in a minipig model within an observation period of 8 weeks. Immunohistochemically, Collagen I/III ratio as a marker of tissue integration was significantly higher in TPU-group versus PVDF group (9.4 ± 0.5 vs. 8.1 ± 0.5, p = 0.002) with a significantly lower inflammatory reaction measured by a smaller inner granuloma at mesh-colon interface (17.6 ± 3.3 μm vs. 23 ± 5 μm, p < 0.001). A new TPU/PVDF composite mesh with enhanced elastic properties as IPST was created. Stoma surgery and especially the evaluation of the new stoma mesh prosthesis are feasible with reproducible results in an animal model. Tissue integration expressed by Collagen I/III ratio seems to be improved in comparison to standard-elastic PVDF-IPST meshes.

Intraabdominelle Blutungen sind am haufigsten traumatisch oder postoperativ/-interventionell bedingt. Diagnostik und Therapie werden in Sektion II „Trauma“ und Sektion III „Erkrankungen und Komplikationen“ organspezifisch erlautert.

The Pringle maneuver (PM) has been widely used to control blood loss during liver resection. However, hepatic inflow occlusion can also result in hepatic ischemia&ndash, reperfusion injury (IRI), especially in patients with a cholestatic, fibrotic, or cirrhotic liver. Here we investigate a nitric oxide synthase (NOS) inhibitor N-Nitroarginine methyl ester (L-NAME) on IRI after the PM and partial hepatectomy of cholestatic livers induced by bile duct ligation (BDL) in rats. Control group (non-BDL/no treatment), BDL + T group (BDL/L-NAME treatment) and BDL group (BDL/no treatment) were analyzed. Cholestasis was induced by BDL in the L-NAME and BDL group and a 50% partial hepatectomy with PM was performed. L-NAME was injected before PM in the BDL + T group. Hepatocellular damage, portal venous flow, microcirculation, endothelial lining, and eNOS, iNOS, interleukin (IL)-6, and transforming growth factor-&beta, (TGF-&beta, ) were evaluated. Microcirculation of the liver in the BDL + T group tended to be higher. Liver damage and apoptotic index were significantly lower and Ki-67 labeling index was higher in the BDL + T group while iNOS and TGF-&beta, expression was decreased. This was corroborated by a better preserved endothelial lining. L-NAME attenuated IRI following PM and improved proliferation/regeneration of cholestatic livers. These positive effects were considered as the result of improved hepatic microcirculation, prevention of iNOS formation, and TGF-&beta, mRNA upregulation.

Background The nuclear factor-erythroid 2-related factor 2 (Nrf2) -antioxidant response element (ARE) pathway is important for the regulation of antioxidative stress response and detoxification. To activate the expression of its target genes, such as heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase (quinone) 1 (NQO1), Nrf2 binds to the ARE within the promoter region of these genes. Partial hepatectomy and consecutive liver regeneration lead to oxidative stress with activation of the Nrf2-ARE pathway. The aim of this study was to investigate ARE activity in vivo during liver regeneration after partial hepatectomy. Materials and methods Transgenic ARE-luc mice were used. In these mice, the luciferase reporter gene is under the control of an ARE promoter element. Following 2/3 partial hepatectomy (PHx), mice underwent in vivo bioluminescence imaging up until the ninth postoperative day. In addition, liver tissue was analyzed by immunohistochemistry (Nrf2 and HO-1), quantitative reverse transcription-PCR (HO-1 and NQO1) and in vitro luminescence assays. Results Bioluminescence imaging revealed a significant increase in Nrf2-ARE activity after PHx. The signal maximum was recorded on the third day after PHx. Seven days postoperatively, the signal almost reached baseline levels. In immunohistochemistry, significantly more hepatocytes were positive for Nrf2 and HO-1 on the third postoperative day compared with baseline levels. The mRNA expression of HO-1 and NQO1 were significantly increased on day 3 as measured by qRT-PCR. Conclusions This study demonstrated the time-dependent activation of the Nrf2-ARE system during liver regeneration in vivo. The transgenic ARE-luc mouse provided a convenient model for studying Nrf2-mediated gene expression noninvasively and may facilitate further experiments with therapeutic modulation of the antioxidative stress response.

Introduction: Worldwide, more than 20 million patients undergo groin hernia repair annually. The many different approaches, treatment indications and a significant array of techniques for groin hernia repair warrant guidelines to standardize care, minimize complications, and improve results. The main goal of these guidelines is to improve patient outcomes, specifically to decrease recurrence rates and reduce chronic pain, the most frequent problems following groin hernia repair. They have been endorsed by all five continental hernia societies, the International Endo Hernia Society and the European Association for Endoscopic Surgery. Methods: An expert group of international surgeons (the HerniaSurge Group) and one anesthesiologist pain expert was formed. The group consisted of members from all continents with specific experience in hernia-related research. Care was taken to include surgeons who perform different types of repair and had preferably performed research on groin hernia surgery. During the Group’s first meeting, evidence-based medicine (EBM) training occurred and 166 key questions (KQ) were formulated. EBM rules were followed in complete literature searches (including a complete search by The Dutch Cochrane database) to January 1, 2015 and to July 1, 2015 for level 1 publications. The articles were scored by teams of two or three according to Oxford, SIGN and Grade methodologies. During five 2-day meetings, results were discussed with the working group members leading to 136 statements and 88 recommendations. Recommendations were graded as “strong” (recommendations) or “weak” (suggestions) and by consensus in some cases upgraded. In the Results and summary section below, the term “should” refers to a recommendation. The AGREE II instrument was used to validate the guidelines. An external review was performed by three international experts. They recommended the guidelines with high scores. Results and summary: The risk factors for inguinal hernia (IH) include: family history, previous contra-lateral hernia, male gender, age, abnormal collagen metabolism, prostatectomy, and low body mass index. Peri-operative risk factors for recurrence include poor surgical techniques, low surgical volumes, surgical inexperience and local anesthesia. These should be considered when treating IH patients. IH diagnosis can be confirmed by physical examination alone in the vast majority of patients with appropriate signs and symptoms. Rarely, ultrasound is necessary. Less commonly still, a dynamic MRI or CT scan or herniography may be needed. The EHS classification system is suggested to stratify IH patients for tailored treatment, research and audit. Symptomatic groin hernias should be treated surgically. Asymptomatic or minimally symptomatic male IH patients may be managed with “watchful waiting” since their risk of hernia-related emergencies is low. The majority of these individuals will eventually require surgery; therefore, surgical risks and the watchful waiting strategy should be discussed with patients. Surgical treatment should be tailored to the surgeon’s expertise, patient- and hernia-related characteristics and local/national resources. Furthermore, patient health-related, life style and social factors should all influence the shared decision-making process leading up to hernia management. Mesh repair is recommended as first choice, either by an open procedure or a laparo-endoscopic repair technique. One standard repair technique for all groin hernias does not exist. It is recommended that surgeons/surgical services provide both anterior and posterior approach options. Lichtenstein and laparo-endoscopic repair are best evaluated. Many other techniques need further evaluation. Provided that resources and expertise are available, laparo-endoscopic techniques have faster recovery times, lower chronic pain risk and are cost effective. There is discussion concerning laparo-endoscopic management of potential bilateral hernias (occult hernia issue). After patient consent, during TAPP, the contra-lateral side should be inspected. This is not suggested during unilateral TEP repair. After appropriate discussions with patients concerning results tissue repair (first choice is the Shouldice technique) can be offered. Day surgery is recommended for the majority of groin hernia repair provided aftercare is organized. Surgeons should be aware of the intrinsic characteristics of the meshes they use. Use of so-called low-weight mesh may have slight short-term benefits like reduced postoperative pain and shorter convalescence, but are not associated with better longer-term outcomes like recurrence and chronic pain. Mesh selection on weight alone is not recommended. The incidence of erosion seems higher with plug versus flat mesh. It is suggested not to use plug repair techniques. The use of other implants to replace the standard flat mesh in the Lichtenstein technique is currently not recommended. In almost all cases, mesh fixation in TEP is unnecessary. In both TEP and TAPP it is recommended to fix mesh in M3 hernias (large medial) to reduce recurrence risk. Antibiotic prophylaxis in average-risk patients in low-risk environments is not recommended in open surgery. In laparo-endoscopic repair it is never recommended. Local anesthesia in open repair has many advantages, and its use is recommended provided the surgeon is experienced in this technique. General anesthesia is suggested over regional in patients aged 65 and older as it might be associated with fewer complications like myocardial infarction, pneumonia and thromboembolism. Perioperative field blocks and/or subfascial/subcutaneous infiltrations are recommended in all cases of open repair. Patients are recommended to resume normal activities without restrictions as soon as they feel comfortable. Provided expertise is available, it is suggested that women with groin hernias undergo laparo-endoscopic repair in order to decrease the risk of chronic pain and avoid missing a femoral hernia. Watchful waiting is suggested in pregnant women as groin swelling most often consists of self-limited round ligament varicosities. Timely mesh repair by a laparo-endoscopic approach is suggested for femoral hernias provided expertise is available. All complications of groin hernia management are discussed in an extensive chapter on the topic. Overall, the incidence of clinically significant chronic pain is in the 10–12% range, decreasing over time. Debilitating chronic pain affecting normal daily activities or work ranges from 0.5 to 6%. Chronic postoperative inguinal pain (CPIP) is defined as bothersome moderate pain impacting daily activities lasting at least 3 months postoperatively and decreasing over time. CPIP risk factors include: young age, female gender, high preoperative pain, early high postoperative pain, recurrent hernia and open repair. For CPIP the focus should be on nerve recognition in open surgery and, in selected cases, prophylactic pragmatic nerve resection (planned resection is not suggested). It is suggested that CPIP management be performed by multi-disciplinary teams. It is also suggested that CPIP be managed by a combination of pharmacological and interventional measures and, if this is unsuccessful, followed by, in selected cases (triple) neurectomy and (in selected cases) mesh removal. For recurrent hernia after anterior repair, posterior repair is recommended. If recurrence occurs after a posterior repair, an anterior repair is recommended. After a failed anterior and posterior approach, management by a specialist hernia surgeon is recommended. Risk factors for hernia incarceration/strangulation include: female gender, femoral hernia and a history of hospitalization related to groin hernia. It is suggested that treatment of emergencies be tailored according to patient- and hernia-related factors, local expertise and resources. Learning curves vary between different techniques. Probably about 100 supervised laparo-endoscopic repairs are needed to achieve the same results as open mesh surgery like Lichtenstein. It is suggested that case load per surgeon is more important than center volume. It is recommended that minimum requirements be developed to certify individuals as expert hernia surgeon. The same is true for the designation “Hernia Center”. From a cost-effectiveness perspective, day-case laparoscopic IH repair with minimal use of disposables is recommended. The development and implementation of national groin hernia registries in every country (or region, in the case of small country populations) is suggested. They should include patient follow-up data and account for local healthcare structures. A dissemination and implementation plan of the guidelines will be developed by global (HerniaSurge), regional (international societies) and local (national chapters) initiatives through internet websites, social media and smartphone apps. An overarching plan to improve access to safe IH surgery in low-resource settings (LRSs) is needed. It is suggested that this plan contains simple guidelines and a sustainability strategy, independent of international aid. It is suggested that in LRSs the focus be on performing high-volume Lichtenstein repair under local anesthesia using low-cost mesh. Three chapters discuss future research, guidelines for general practitioners and guidelines for patients. Conclusions: The HerniaSurge Group has developed these extensive and inclusive guidelines for the management of adult groin hernia patients. It is hoped that they will lead to better outcomes for groin hernia patients wherever they live. More knowledge, better training, national audit and specialization in groin hernia management will standardize care for these patients, lead to more effective and efficient healthcare and provide direction for future research.

In hernia surgery, meshes with small pores tend to be filled by fibrous tissue, which reduces their stretchability and causes patient complaints. Because of the inelasticity of current meshes, mechanical strain might cause pores to collapse even in large-pore mesh constructions. In this study, a mesh with elastic thermoplastic polyurethane (TPU) filaments was constructed to prevent pore size changes even under mechanical strain, and its biocompatibility in comparison with polyvinylidene fluoride (PVDF) was evaluated. A mesh was constructed using PVDF with elastic TPU filaments and mechanically tested. After midline laparotomy in 20 rabbits, we placed a 15 cm × 3 cm mesh as inlay in the defect. Animals were randomized to either the TPU or PVDF group. After 7 or 21 days, mesh expansion was measured under pneumoperitoneum, and abdominal walls were explanted for immunohistochemical investigations. In vitro, TPU meshes showed a slight reduction in effective porosity from 46% at tension-free conditions to 26% under longitudinal and to 34% under transverse strain. The nonelastic PVDF meshes showed a marked reduction in effective porosity from 70% to 7% and 52%, respectively. The TPU mesh had a breaking elongation of 101% and a tensile strength of 35 N/cm. In vivo, both meshes achieved healing of the incision without hernial defect. The TPU mesh maintained its elasticity under pneumoperitoneum. The amount of CD68-positive, Ki67-positive, and apoptotic cells was significantly lower in the TPU group after 7 and 21 days. The newly developed TPU mesh shows elasticity, structural stability, and preserved effective porosity under mechanical strain. Immunohistochemistry indicates superior biocompatibility of TPU mesh compared with PVDF after 7 and 21 days.

Background: Biocompatibility and tissue integration of a surgical suture are decisive factors for wound healing and therefore for the success of sutures. The optimal suture material is still under discussion. Polyvinylidene fluoride (PVDF) is described to have superior properties of biocompatibility and is therefore frequently used as a mesh component. Only little information is available about its use as a suture material. The aim of this study was to evaluate the biocompatibility of PVDF as a suture material in comparison to 5 different established sutures in a rat model. Methods: In 30 male rats, a monofilamental PVDF suture (Resopren®) and 5 established control suture materials [polyester (Miralene®), polytetrafluoroethylene (Gore®), poliglecaprone (Monocryl®), polydioxanone (Monoplus®), polyglactin 910 (Vicryl®), USP size 3-0] were placed in the subcutaneous layer of the abdominal wall without knot or tension. After 3, 7 or 21 days, the abdominal walls were explanted for histopathological and immunohistochemical investigation with special regard to the size and quality of foreign body granuloma and the length of the comet tail-like infiltrate (CTI). Results: The PVDF sutures showed the smallest size of foreign body granuloma (60 ± 14 µm) and the smallest CTI length (343 ± 60 µm) of all polymers after 21 days. Only PVDF (Resopren) and polydioxanone (Monoplus) showed a significant collagen I/III ratio increase between days 3 and 21 (p = 0.009 and p = 0.016). The quality of foreign body reaction regarding inflammation, proliferation and fibrotic remodeling was similar between all suture materials. Conclusions: Our data indicate that monofilamental PVDF sutures show a favorable foreign body reaction with small granuloma sizes and CTI length in comparison to established sutures. Its use as a suture material in general surgery could therefore be extended in the future. To reinforce these findings, further clinical studies need to be conducted.

INTRODUCTION: Mesh infection is a severe complication after incisional hernia repair and occurs in 1-3 % of all open mesh implantations. For this reason, topical antimicrobial agent applied directly to the mesh is often used procedure. So far, however, this procedure lacks a scientific basis.MATERIALS AND METHODS: Two different meshes (Parietex™, Covidien; Ultrapro™, Ethicon Johnson & Johnson) were incubated with increasing amounts of three different Staphylococcus aureus strains (ATCC 25923; Mu50; ST239) with or without gentamicin and growth ability were determined in vitro. To further address the question of the systemic impact of topic gentamicin, serum levels were analyzed 6 and 24 h after implantation of gentamicin-impregnated multifilament meshes in 19 patients.RESULTS: None of the gentamicin-impregnated meshes showed any bacterial growth in vitro. This effect was independent of the mesh type for all the tested S. aureus strains. In the clinical setting, serum gentamicin levels 6 h after implantation of the gentamicin-impregnated meshes were below the through-level (range 0.4-2.9 mg/l, mean 1.2 ± 0.7 mg/l). After 24 h the gentamicin serum levels in all patients had declined 90-65 % of the 6 h values.CONCLUSION: Local application of gentamicin to meshes can completely prevent the growth of even gentamicin-resistant S. aureus strains in vitro. The systemic relevance of gentamicin in the clinical controls showed to be very low, without reaching therapeutic concentrations.

Shrinkage and deformation of mesh implants used for hernia treatment can be the cause of long-term complications. The purpose of this study was to quantify noninvasively time-dependent mesh shrinkage, migration, and configuration changes in patients who were surgically treated for inguinal hernia using magnetic resonance imaging (MRI)-visible mesh implants.In an agarose phantom, meshes in different shrinkage and folding conditions were used to validate the quantification process. Seven patients who were surgically (3 bilaterally) treated for inguinal hernia using iron-loaded mesh implants were prospectively examined using MRI. Gradient echo sequences in sagittal and transverse orientations were performed on day 1 after surgery and at day 90. The mesh-induced signal voids were semiautomatically segmented and a polygonal surface model was generated. A comparison of area and centroid position was performed between the 2 calculated surfaces (day 1 vs day 90).The phantom study revealed a maximum deviation of 3.6% between the MRI-based quantification and the actual mesh size. All 10 implants were successfully reconstructed. The mean (SD) observed mesh shrinkage 90 days after surgery was 20.9% (7.1%). The mean (SD) centroid movement was 1.17 (0.47) cm. Topographic analysis revealed mean (SD) local configuration changes of 0.23 (0.03) cm.In this study, significant mesh shrinkage (20.9%) but marginal changes in local mesh configuration occurred within 90 days after mesh implantation. Centroid shift of the mesh implant can be traced back to different patient positioning and abdominal distension. The developed algorithm facilitates noninvasive assessment of key figures regarding MRI-visible meshes. Consequently, it might help to improve mesh technology as well as surgical skills.

Institut fuer Textiltechnik at RWTH Aachen University, Aachen, GermanyReceived 6 January 2014; revised 25 April 2014; accepted 17 May 2014Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.b.33222Abstract: Background: Midline laparotomy wound failure likeburst abdomen remains one of the major complications afterabdominal surgery. The use of sutures with a closer resem-blance to abdominal wall physiology, like elastic threads,could decrease the risk of these complications occurring.Thus, we evaluated the possibility of using a new elasticthread composed of thermoplastic polyurethane (TPU) as asuture for the closure of midline laparotomies compared toconventionally used polypropylene (PP) in a rabbit model.Methods: The elastic TPU thread was processed and tensiletests were performed. Twenty female chinchilla rabbitsunderwent midline laparotomy. They were randomized to aTPU and a PP group depending on the suture used for fasciaclosure. After 7 or 21 days, the abdominal walls wereassessed macroscopically for wound healing complicationsand were explanted for histopathological investigation.Results: Tensile tests showed a mean elastic elongation of55.5% and a sufficient material strength of the TPU thread. Inanimal experiments, there was no difference between thegroups at 7 days; however, the TPU suture showed signifi-cantly less CD68 positive cells (p

Recurrence rate of hiatal hernia can be reduced with prosthetic mesh repair; however, type and shape of the mesh are still a matter of controversy. The purpose of this study was to investigate the biomechanical properties of four conventional meshes: pure polypropylene mesh (PP-P), polypropylene/poliglecaprone mesh (PP-U), polyvinylidenefluoride/polypropylene mesh (PVDF-I), and pure polyvinylidenefluoride mesh (PVDF-S). Meshes were tested either in warp direction (parallel to production direction) or perpendicular to the warp direction. A Zwick testing machine was used to measure elasticity and effective porosity of the textile probes. Stretching of the meshes in warp direction required forces that were up to 85-fold higher than the same elongation in perpendicular direction. Stretch stress led to loss of effective porosity in most meshes, except for PVDF-S. Biomechanical impact of the mesh was additionally evaluated in a hiatal hernia model. The different meshes were used either as rectangular patches or as circular meshes. Circular meshes led to a significant reinforcement of the hiatus, largely unaffected by the orientation of the warp fibers. In contrast, rectangular meshes provided a significant reinforcement only when warp fibers ran perpendicular to the crura. Anisotropic elasticity of prosthetic meshes should therefore be considered in hiatal closure with rectangular patches.

Background: Application of a mesh in presence of pneumoperitoneum may cause deformation or wave formation when gas is released. Moreover, mesh shrinkage during subsequent wound healing cannot be detected in vivo without invasive diagnostics. Using MRI-visible polyvinylidene fluoride (PVDF) mesh, the extend of mesh deformation and shrinkage could be objectified by MRI for the first time. Materials and Methods: Laparoscopic intraperitoneal onlay mesh (IPOM) implantation was performed in 10 female rabbits using ferro-oxide loaded PVDF meshes. MRI measurements were performed postoperatively at days 1 and 90. After three-dimensional reconstruction of all MRI images the total surface and the effective surface of the implanted mesh were explored and calculated computer-assisted. Results: In all cases, the mesh could be identified in MRI. The subsequent three-dimensional reconstruction always allowed a calculation of the mesh area. In relation to the original size of the used textile implant, we found neither a significant reduction of the effective mesh surface after release of the pneumoperitoneum at day 1 after laparoscopic surgery nor a significant change of the total surface of this large pore mesh by the end of the observation period. Conclusions: In vivo investigation of mesh surface via MRI could exclude a significant initial reduction of the effective mesh surface after release of pneumoperitoneum, in this IPOM rabbit model. A further subsequent shrinkage of these large pore PVDF meshes could be excluded, as well. Imaging of MRI-visible IPOM mesh turned out to be a sufficient tool to objectify mesh configuration and position in vivo. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1165–1169, 2014.

Das Risiko fur eine postoperative Komplikation kann im Rahmen eines grosen Operationstraumas, bei Patienten mit einer beeintrachtigen Wundheilung oder bei der Verwendung eines ungeeigneten Netzmaterials steigen. Unserem Zugriff zuganglich ist dabei neben der Optimierung der chirurgischen Technik die gezielte Auswahl eines geeigneten Implantates. Generell ist bei grosporigen, monofilen Netzimplantaten mit einer geringeren Entzundungs- und Narbenreaktion zu rechnen, die beide masgeblich zu funktionellen Einschrankungen fuhren konnen. Die Ausbildung intraabdomineller Adhasionen zu einem intraperitonealen Netz ist angesichts des begleitenden Operationstraumas nicht zu vermeiden, wohl dagegen das Risiko fur Fistelbildungen, wenn auf die Einlage ungeschutzter Polypropylennetze verzichtet wird. Das Risiko fur Schmerzen durch die Narbenbildung bzw. -kontraktur lasst sich durch Einsatz grosporiger Materialien reduzieren. Die Rezidivgefahr wird vornehmlich durch die Netzgrose bestimmt, die technischen Schwierigkeiten fur eine ausreichende Unterfutterung konnen jedoch bei sehr flexiblen Materialien eine Anpassung der Operationstechnik erfordern. Bei bakteriell kontaminierten Wundverhaltnissen ist stets eine verzogert auftretende Implantatinfektion zu befurchten. Eine erfolgreiche konservative Therapie ist am ehesten bei monofilen Implantaten moglich. Eine vom Operationstrauma unabhangige zusatzliche materialbedingte Storung der Samenstrangfunktion lasst sich derzeit nicht belegen. Revisionseingriffe nach Implantation einer Netzprothese stellen grundsatzlich eine chirurgische Herausforderung dar, speziell jedoch im Zwerchfell-, Beckenboden- oder Leistenbereich. Hier konnen in Zukunft moglicherweise Implantate helfen, die in der ublichen Diagnostik auch darstellbar sind.

Purpose:Evaluation of hernia therapies according to the current rules of Evidence Based Medicine is widely reduced to results of RCTs or meta-analyses. RCTs have been accepted as a most important tool to confirm a superior effect of an intervention. Unfortunately, in hernia surgery, comparisons of RCTs and correspondingly their use in meta-analyses, are not, surprisingly often, able to confirm any significant impact of a specific procedure due to intrinsic restrictions in a multi-causal setting with its web of influences. Methods:Based on our own experiences of clinical studies in surgery, the present article outlines several situations, with their respective reasons, which argue the severe limitations of RCTs and meta-analysis to define an optimum treatment. Results:Meta-analyses accumulate the variations of each trial, which then may cover any clear causal relationship. RCTs usually are dealing with subgroups of standard patients thus excluding the majority of our patients. Low statistical power of current cohort sizes restricts the analysis of subgroups or of effects with low incidences. Simple comparisons of means frequently are hampered by nonlinear relationships to outcome. The relevance of a specific variable is difficult to separate from other influences. The limited surveillance period of studies ignores a delayed change in outcome. Randomization cannot guarantee a standardized patient’s condition. All the arguments have to be considered as a crucial and fundamental consequence of the bias-variance dilemma or principle of uncertainty in medicine, and underline the many limitations of RCTs to evaluate any specific impact of hernia therapies on e.g. infection, pain or recurrence. Conclusions: Many surgical issues cannot be and should not be investigated by RCTs, in particular, if a marked patients’ heterogeneity has to be considered or the low incidences of the outcome readout cannot be addressed with sufficient statistical power without getting lost in the variation mire. Registries with their non-restricted data-acquisition should be regarded as reliable alternatives for postoperative outcome quality surveillance studies.

Background: Ischemia/reperfusion injury (IRI) is one of the major clinical problems in liver and transplant surgery. Livers subjected to warm ischemia in vivo often show a severe dysfunction and the release of numerous inflammatory cytokines and arachidonic acid metabolites. Cyclooxygenase (COX)-2 is the inducible isoform of an intracellular enzyme that converts arachidonic acid into prostaglandins. The aim of the study was to evaluate the effect of COX-2 inhibition and the role of Kupffer cells in IRI of the liver. Methods: Male Wistar rats [250- 280 g body weight (BW)] were anesthetized and subjected to 30-min warm ischemia of the liver (Pringle's maneuver) and 60-min reperfusion after median laparotomy. The I/R group received no additional treatment. In the COX-2 inhibitor (COX-2I) group, the animals received 1 mg/kg BW meloxicam prior to operation. Gadolinium chloride (GdCl3) (10 mg/kg BW) was given 24 h prior to operation in the GdCl3 and GdCl3 + COX-2I groups for the selective depletion of Kupffer cells. The GdCl3 + COX-2I group received both GdCl3 and meloxicam treatment prior to operation. Blood and liver samples were obtained at the end of the experiments for further investigations. Results: After 30 min of warm ischemia in vivo, severe hepatocellular damage was observed in the I/R group. These impairments could be significantly prevented by the selective COX-2 inhibition and the depletion of Kupffer cells. Alanine aminotransferase was significantly reduced upon meloxicam and GdCl3 treatment compared to the I/R group: I/R, 3,240 ± 1,262 U/l versus COX-2I, 973 ± 649 U/l, p < 0.001; I/R versus GdCl3, 1,611 ± 600 U/l, p < 0.05, and I/R versus GdCl3 + COX-2I, 1,511 ± 575 U/l, p < 0.01. Plasma levels of tumor necrosis factor alpha (TNF-α) were significantly reduced in the COX-2I treatment group compared to I/R (3.5 ± 1.5 vs. 16.3 ± 11.7 pg/ml, respectively; p < 0.05). Similarly, the amount of TxB2, a marker for COX-2 metabolism, was significantly reduced in the meloxicam treatment groups compared to the I/R group: I/R, 22,500 ± 5,210 pg/ml versus COX-2I, 1,822 ± 938 pg/ml, p < 0.001, and I/R versus GdCl3 + COX-2I, 1,530 ± 907 pg/ml, p < 0.001. All values are given as mean ± SD (n = 6). Conclusion: These results suggest that the inhibition of COX-2 suppressed the initiation of an inflammatory cascade by attenuating the release of TNF-α, which is an initiator of the inflammatory reaction in hepatic IRI. Therefore, we conclude that preferential inhibition of COX-2 is a possible therapeutic approach against warm IRI of the liver.

Textile meshes frequently are implanted in the abdominal wall to reinforce a hernia repair. However, revisions for mesh associated complications confirm that these devices are not completely free of risk. Explanted devices offer an opportunity to define the impact of mesh structure on tissue response. This retrieval study analyses the tissue reaction to 623 polypropylene mesh samples (170 class 1 with large pores, and 453 class 2 with small pores) explanted for pain, infection, or recurrence. Histopathological assessment included morphometry of inflammatory infiltrate (IF) and connective tissue (CT), and of collagen 1/3 ratio. Half of the meshes were removed after more than 23 month. Despite large inter-individual differences removal for infection showed more IF than for pain or recurrence with significant correlation of IF with CT. Class 1 meshes with large pores showed less IF, CT, fistula formation, calcification, and bridging than class 2 meshes with small pores. Meshes removed for recurrence showed a lowered collagen 1/3 ratio in 70%. Large pore class 1 meshes showed an improved tissue response and may be considered as favorable to prevent inflammatory side effects. The presence of lowered collagen 1/3 ratio in most of the samples with recurrences stresses the relevance of an intact healing process. Late manifestation of complications demands long-lasting follow-up. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

An altered collagen metabolism could play an important role in hernia development. This study compared collagen type I/III ratio and organisation between hernia and control patients, and analysed the correlation in collagen type I/III ratio between skin and abdominal wall fascia.Collagen organisation was analysed in Haematoxylin-Eosin sections of anterior rectus sheath fascia, and collagen type I/III ratio, by crosspolarisation microscopy, in Sirius-Red sections of skin and anterior rectus sheath fascia, of 19 control, 10 primary inguinal, 10 recurrent inguinal, 13 primary incisional and 8 recurrent incisional hernia patients.Compared to control patients [7.2 (IQR = 6.8-7.7) and 7.2 (IQR = 5.8-7.9)], collagen type I/III ratio was significantly lower in skin and anterior rectus sheath fascia of primary inguinal [5.2 (IQR = 3.8-6.3) and 4.2 (IQR = 3.8-4.7)], recurrent inguinal [3.2 (IQR = 3.1-3.6) and 3.3 (IQR = 3-3.7)], primary incisional [3.5 (IQR = 3-3.9) and 3.4 (IQR = 3.3-3.6)] and recurrent incisional hernia [3.2 (IQR = 3.1-3.9) and 3.2 (IQR = 2.9-3.2)] patients; also incisional and recurrent inguinal hernia had lower ratio than primary inguinal hernia patients. Furthermore, collagen type I/III ratio was significantly correlated (r = 0.81; P0.001) between skin and anterior rectus sheath fascia. Finally, collagen organisation was comparable between hernia and control patients.Furthermore, in both skin and abdominal wall fascia of hernia patients, collagen type I/III ratio was lower compared to control patients, with more pronounced abnormalities in incisional and recurrent inguinal hernia patients. Importantly, collagen type I/III ratio in skin was representative for that in abdominal wall fascia.

Background Postsurgical adhesions severely affect the patients' quality of life causing various complications like bowel obstruction or chronic pain. Especially the implantation of alloplastic prostheses in IPOM position for hernia repair carries a high risk of adhesion formation due to the close contact between mesh and viscera. The extent of adhesions mainly depends on the type and textile characteristics of the implanted mesh. The aim of this study was to examine the degree of adhesion formation of a newly developed, elastic thermoplastic polyurethane (TPU) mesh in comparison to polypropylene (PP) meshes in IPOM position in a rabbit model. Methods Sixteen female chinchilla rabbits were laparoscopically operated. Two different meshes were placed to the left and the right lower abdominal wall in IPOM position in each rabbit. After 7 or 21 days, midline laparotomy was performed, the degree of adhesion formation was examined by the Diamond score and mesh elongation was measured under a force of 3 N. Finally, the abdominal walls were explanted for immunohistochemical and histopathological investigations. Results TPU meshes showed significantly lower Diamond scores than PP meshes. After explantation, mesh elongation of the TPU mesh was significantly larger than expansion of PP under a force of 3 N. Thus, the TPU mesh preserved its elastic properties after 7 and 21 days. The amount of CD68 positive, Ki67 positive and apoptotic cells within the granuloma around the fibers did not show significant differences between the study groups. Conclusions The newly developed TPU mesh seems to reduce peritoneal adhesion formation in IPOM position in a rabbit model compared to PP meshes after 7 and 21 days. Immunohistochemistry did not reveal differences in biocompatibility of the two meshes used.

The impact of surgical staplers on tissues has been studied mostly in an empirical manner. In this paper, finite element method was used to clarify the mechanics of tissue stapling and associated phenomena. Various stapling modalities and several designs of circular staplers were investigated to evaluate the impact of the device on tissues and mechanical performance of the end-to-end colorectal anastomosis. Numerical simulations demonstrated that a single row of staples is not adequate to resist leakage due to non-linear buckling and opening of the tissue layers between two adjacent staples. Compared to the single staple row configuration, significant increase in stress experienced by the tissue at the inner staple rows was observed in two and three rows designs. On the other hand, adding second and/or third staple row had no effect on strain in the tissue inside the staples. Variable height design with higher staples in outer rows significantly reduced the stresses and strains in outer rows when compared to the same configuration with flat cartridge.