[Perforation as a delayed complication after endoscopic full-thickness resection in a recurrent adenoma of the sigmoid]. / Perforation als Spätkomplikation nach endoskopischer Vollwandresektion eines Rezidivadenoms im Colon sigmoideum.

The endoscopic full-thickness resection (EFTR) is established in ablation of recurrent colorectal adenomas, which cannot be removed by endoscopic resection in cases of fibrosis. The EFTR can be applied with low risk, in one step, with the use of special devices, such as the full-thickness resection device (FTRD®). The main risks described in literature are bleeding and perforations. The mentioned perforations were explained by previous defects of the device system or patient-related predisposed parameters for perforation.We report the case of a 55-year old woman who underwent an endoscopic full-thickness resection with the FTRD® due to a recurrent adenoma with high-grade intraepithelial neoplasm in the sigmoid. After primary uncomplicated development, she presented with a secondary perforation with purulent peritonitis seven days after intervention, so a sigmoid-resection was necessary. There were no signs of defects with the FTRD® system or patient-related predisposed parameters, which prefer a perforation.Our case-report demonstrates the necessity for clinical follow up, after primary uncomplicated endoscopic full-thickness resection, to recognize delayed complications.

Video-assisted hepatic abscess debridement.

BACKGROUND: Pyogenic liver abscesses are currently treated by either percutaneous computer tomography (CT)-guided drainage or by laparoscopic and a conventional liver resection when conservative treatment fails but may be associated with substantial morbidity and mortality. METHODS: A minimally invasive technique involving debridement of right liver abscesses was employed using a minimally invasive video-assisted hepatic abscess debridement (VAHD) after unsuccessful percutaneous CT-guided drainage. Clinical data, complication rates and outcomes of patients were recorded retrospectively. RESULTS: Between 2011 and 2014, VAHD was performed on 10 patients at two centres with no observed recurrence of a liver abscess. The median age of the patients was 57 years (range 42-78) with a median pre-operative size of a liver abscess of 78 mm (range 40-115). The median operation time was 47 min (range 23-75), and the median postoperative hospital stay was 9 days (range 7-69). One patient developed a subcutaneous abscess that required further surgery. No patient died, and there were no major complications related to the VAHD. CONCLUSIONS: Video-assisted hepatic abscess debridement is a feasible technique that shows promising results for the treatment of a recurrent right liver abscess.

Laser-induced drug release for local tumor control--a proof of concept.

BACKGROUND: The systemic palliative chemotherapy of locally extended gastrointestinal and hepatobiliary tumors is associated with a considerable burden for the patient. The aim of this project was to develop a new drug release system to improve the local stent therapy in these patients as a proof of concept study. For this purpose, polymer filaments were modified with drug-loaded polymer microgels that allow selective release of the active substance by photochemical triggering using laser radiation. Integrated into a stent system, the better local tumor control could thus contribute to a significant increase in the quality of life of patients. METHODS: A standard mammalian cell line and two carcinoma cell lines were established. By Fluorescence activated cell sorting (FACS), the cytotoxicity of the different materials was determined in vitro before and after drug loading with the chemotherapeutic agent 5-Fluorouracil (5-FU). For this purpose, the locally applied 5-FU concentration was previously determined by Bromdesoxyuridin assay. 5-FU dimer was synthesized by photo-induced dimerization of 5-FU in the presence of benzophenone in methanol. The chemical structure of 5-FU dimer was confirmed with Hydrogen-1 nuclear magnetic resonance and Fluorine-19 nuclear magnetic resonance. 5-FU dimer is nonsoluble in water and can be easily incorporated in polymer microgels modified with hydrophobic binding domains (cyclodextrin). After laser irradiation, 5-FU dimer decomposes and 5-FU can be released from microgels. Finally, the measurements were repeated after this laser-induced drug release. RESULTS: In FACS analysis, neither the microgels nor the microgel cumarin complexes showed a significant difference in comparison with the negative control with H2O and therefore no toxic effect on the cell lines. After loading with the 5-FU dimer, there was no significant cell death (contrary to the pure 5-FU monomer, which dose had been previously tested as highly toxic). After laser-induced dissociation back to monomer and the associated drug release, FACS analysis showed cytotoxicity. CONCLUSIONS: It was possible to develop 5-FU dimerloaded microgels, which show no cytotoxic effect on cell lines before laser irradiation. After dissociation back to 5-FU monomer by selective photochemical triggering using laser irradiation, the active substance was released. Thus, a new drug release system has been created and tested in vitro. For further development, integration into a stent system and for in vivo follow-up evaluation more studies need to be conducted.

Influence of CD68+ macrophages and neutrophils on anastomotic healing following laparoscopic sigmoid resection due to diverticulitis.

BACKGROUND: The aim of this prospective study was to evaluate the predictive value of a potential preexisting low-grade inflammation regarding the incidence of anastomotic leakage in elective laparoscopic sigmoid resection due to diverticulitis. METHODS: Patients with either chronically recurrent diverticulitis or sigmoid stenosis caused by chronic diverticulitis were included in this study. All patients with acute local or systemic inflammation were excluded. Detailed patient information (e.g. American Society of Anesthesiologists (ASA) grade, comorbidities, duration of hospital stay, and anastomotic leakage) was prospectively recorded. CD68(+) macrophages, neutrophils, CD3(+) T-lymphocytes, CD11c(+) dendritic cells, MHCII, TNFR1, and NF-κB were evaluated by immunohistochemistry within the acquired sample of colonic bowel wall tissue. Clinical and immunohistochemical data was compared between groups (leakage vs. no leakage). Additionally, a matched-pair analysis was performed due to the widely heterogeneous groups concerning the number of patients and to minimize the effect of extraneous variables. RESULTS: A total of 83 patients were included in the study, of which 7 patients suffered an anastomotic leakage. Neither the clinical nor the immunohistochemical parameters were significantly different between the groups. The matched-pair analysis revealed a nonsignificant increase in mean duration of hospital stay for the group with anastomotic leakage and a significantly higher percentage of CD68(+) macrophages and neutrophils in the colonic wall obtained at the index operation in both the mucosal and submucosal layers for the leakage group. CONCLUSIONS: A preexisting low-grade inflammation represented by infiltrates of macrophages and neutrophils is a predictor for increased risk of developing colon anastomotic leakage.

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.

Gentamicin supplemented polyvinylidenfluoride mesh materials enhance tissue integration due to a transcriptionally reduced MMP-2 protein expression.

BACKGROUND: A beneficial effect of gentamicin supplemented mesh material on tissue integration is known. To further elucidate the interaction of collagen and MMP-2 in chronic foreign body reaction and to determine the significance of the MMP-2-specific regulatory element (RE-1) that is known to mediate 80% of the MMP-2 promoter activity, the spatial and temporal transcriptional regulation of the MMP-2 gene was analyzed at the cellular level. METHODS: A PVDF mesh material was surface modified by plasma-induced graft polymerization of acrylic acid (PVDF+PAAc). Three different gentamicin concentrations were bound to the provided active sites of the grafted mesh surfaces (2, 5 and 8 µg/mg). 75 male transgenic MMP-2/LacZ mice harbouring the LacZ reporter gene under control of MMP-2 regulatory sequence -1241/+423, excluding the RE-1 were randomized to five groups. Bilateral of the abdominal midline one of the five different meshes was implanted subcutaneously in each animal. MMP-2 gene transcription (anti-ß-galactosidase staining) and MMP-2 protein expression (anti-MMP-2 staining) were analyzed semiquantitatively by immunohistochemistry 7, 21 and 90 days after mesh implantation. The collagen type I/III ratio was analyzed by cross polarization microscopy to determine the quality of mesh integration. RESULTS: The perifilamentary ß-galactosidase expression as well as the collagen type I/III ratio increased up to the 90th day for all mesh modifications, whereas no significant changes could be observed for MMP-2 protein expression between days 21 and 90. Both the 5 and 8 µg/mg gentamicin group showed significantly reduced levels of ß-galactosidase expression and MMP-2 positive stained cells when compared to the PVDF group on day 7, 21 and 90 respectively (5 µg/mg: p < 0.05 each; 8 µg/mg: p < 0.05 each). Though the type I/III collagen ratio increased over time for all mesh modifications significant differences to the PVDF mesh were only detected for the 8 µg/mg group at all 3 time points (p < 0.05 each). CONCLUSIONS: Our current data indicate that lack of RE-1 is correlated with increased mesh induced MMP-2-gene expression for coated as well as for non-coated mesh materials. Gentamicin coating reduced MMP-2 transcription and protein expression. For the 8 µg/mg group this effect is associated with an increased type I/III collagen ratio. These findings suggest that gentamicin is beneficial for tissue integration after mesh implantation, which possibly is mediated via RE-1.

Damage to the spermatic cord by the Lichtenstein and TAPP procedures in a pig model.

BACKGROUND: Mesh implantation is regarded as the standard treatment of inguinal hernias. Obstructive azoospermia induced by mesh implantation is a rare but serious complication. Whether different operative techniques or mesh materials used have an effect on the integrity of the testicle and spermatic cord remains unclear. MATERIALS: In 12 minipigs a bilateral inguinal hernia repair, either open or laparoscopic, was performed using a standard small-pore polypropylene (PP) or large-pore polyvinyliden fluoride (PVDF) mesh. Next to measurement of the testicular size, thermography of the groin and testicle as a parameter for perfusion was performed preoperatively and at a follow-up at 6 months. Obstructions of the vas deferens were estimated radiographically. Testicular function (Johnson score) and mesh integration (granuloma size, apoptotic cells) were analyzed histologically. RESULTS: Mean testicular size did not change significantly in follow-up compared to preoperative values. Technique and mesh material used failed to have a significant influence. Thermography of the groin following the Lichtenstein technique had significantly higher values at follow-up regardless of the mesh used. This could not been shown for laparoscopic treatment. Thermographic measurements at the testicle showed a significantly increased temperature in all groups compared to preoperative measurements. Only the Lichtenstein PP group showed significantly decreased values in testicular function. Quantity and quality of obstructions seen at vasography were most detectable in the Lichtenstein PP group. There was significantly decreased granuloma formation following PVDF mesh implantation compared to the PP mesh group regardless of the technique used. CONCLUSIONS: Both the technique and the mesh material have an impact on integrity of spermatic cord and testicular function. According to the results of this study, the laparoscopic TAPP procedure using a large-pore PVDF mesh has the least effect compared to preoperative values.

Influence of small intestinal serosal defect closure on leakage rate and adhesion formation: a pilot study using rabbit models.

BACKGROUND: The management of small intestinal serosal defects remains controversial. Non-closure of such defects is regarded as a risk factor of fistula formation or intestinal leakage, whereas defect closure with absorbable suture material is potentially associated with adhesion formation. The aim of our pilot study was to evaluate the influence of small intestinal serosal defect closure on peritoneal wound healing, leakage rate, and adhesion formation in a rabbit model. METHODS: Twenty-two male rabbits were randomized into two groups. Following median laparotomy, a standardized small intestinal serosal defect with a diameter of 1 cm was performed. Either the defect was closed by two seromuscular 4/0 polyglactin single sutures (n = 11) or the defect was left open (n = 11). On postoperative day 14, all animals were sacrificed for morphological investigations. Complications and the rate of intestinal leakage were measured. The degree of adhesion formation was measured by computer-assisted planimetry. RESULTS: No animal developed fistula formation or intestinal leakage. Eight (73%) animals of the closure group developed local peritoneal adhesions with a mean size of 39.7 ± 45 mm(2). No animal in the non-closure group revealed local peritoneal adhesions at the defect. However, two (18%) animals in the non-closure group developed peritoneal adhesions distant to the defect with a mean size of 3.5 ± 9 mm(2). Comparing both groups, the size of peritoneal adhesions was significantly higher in the closure group (p = 0.013). CONCLUSIONS: Closure of isolated serosal injuries with resorbable suture material was associated with an adhesion formation in distressing certainty, whereas no leakage or fistula formation could be observed at all. Further studies are needed to clarify the impact of serosal defect closure in particular on leakage rate and fistula formation, e.g., with pre-existing adhesions, in case of multiple serosal injuries or with a pre-existing peritonitis.

Chronological evaluation of inflammatory mediators during peritoneal adhesion formation using a rat model.

PURPOSE: The inflammatory response to peritoneal injury is considered to be of particular importance in adhesion formation. The aim of this study was to investigate the dynamics of inflammatory mediators in peritoneal adhesions. METHODS: In 60 male rats, a peritoneal defect was performed using a standardized cecal abrasion model. On days 3, 5, 14, 30, 60, and 90, ten animals were sacrificed. The expression of five integral mediators for the cellular immune response (macrophages, T lymphocytes), inflammation (COX-2), cell differentiation, and proliferation (ß-catenin, c-myc) in visceral and parietal adhesions were analyzed. RESULTS: A distinct infiltration of macrophages was observed in all animals up to the 90th postoperative day with a peak on day 3 for visceral adhesions (26.3 ± 5.6%) and on day 14 for parietal adhesions (5.1 ± 1.1%). Compared to parietal adhesions, macrophage levels were significantly higher on day 3 (p = 0.001) and 5 (p = 0.002) but significantly lower on days 30, 60, and 90 in visceral adhesions (p = 0.041; p = 0.001; p = 0.017). T lymphocytes were detected over time with the highest levels on day 3 (visceral 4.0 ± 0.7%; parietal 6.7 ± 2.9%). High levels of COX-2 expression could be detected for the whole observation period. Positive expression of both ß-catenin and c-myc was detected in persistent adhesions; however, no expression of c-myc was observed in parietal adhesions. CONCLUSIONS: The inflammatory reaction in adhesions is not limited to the early postoperative phase. Macrophages may be fundamental in triggering adhesions, and the presence of T cells indicates an additional role of the adoptive immune system. Identification of chemokines and chemokine receptors that trigger the cellular immune response might be a potential option to minimize adhesion formation.

Biocompatibility of PLGA/sP(EO-stat-PO)-coated mesh surfaces under constant shearing stress.

BACKGROUND: In order to allow inflammatory response modification and ultimately improvement in tissue remodeling, we developed a new surface modification for meshes that will serve as a carrier for other substances. Biocompatibility is tested in an animal model. METHODS: The animal model for diaphragmatic hernia repair was established in prior studies. Meshes were surface modified with star-configured PEO (polyethylene oxide)-based molecules [sP(EO-stat-PO)]. An electrospun nanoweb of short-term absorbable PLGA (polylactide-co-glycolide) with integrated sP(EO-stat-PO) molecules was applied onto the modified meshes. This coating also served as aerial sealing of the diaphragm. A final layer of hydrogel was applied to the product. Adhesive properties, defect size and mesh shrinkage were determined, and histological and immunohistochemical investigations performed after 4 months. RESULTS: The mean defect size decreased markedly in both modified mesh groups. Histologically and with regard to apoptosis and proliferation rate, smooth muscle cells, collagen I/III ratio and macrophage count, no statistically significant difference was seen between the 3 mesh groups. CONCLUSIONS: In this proof-of-principle investigation, we demonstrate good biocompatibility for this surface-modified mesh compared to a standard polypropylene-based mesh. This new coating represents a promising tool as a carrier for bioactive substances in the near future.

Effect of Aprotinin on Liver Injury after Transplantation of Extended Criteria Donor Grafts in Humans: A Retrospective Propensity Score Matched Cohort Analysis.

The number of patients awaiting liver transplantation still widely exceeds the number of donated organs available. Patients receiving extended criteria donor (ECD) organs are especially prone to an aggravated ischemia reperfusion syndrome during liver transplantation leading to massive hemodynamic stress and possible impairment in organ function. Previous studies have demonstrated aprotinin to ameliorate reperfusion injury and early graft survival. In this single center retrospective analysis of 84 propensity score matched patients out of 274 liver transplantation patients between 2010 and 2014 (OLT), we describe the association of aprotinin with postreperfusion syndrome (PRS), early allograft dysfunction (EAD: INR 1,6, AST/ALT > 2000 within 7-10 days) and recipient survival. The incidence of PRS (52.4% vs. 47.6%) and 30-day mortality did not differ (4.8 vs. 0%; p = 0.152) but patients treated with aprotinin suffered more often from EAD (64.3% vs. 40.5%, p = 0.029) compared to controls. Acceptable or poor (OR = 3.3, p = 0.035; OR = 9.5, p = 0.003) organ quality were independent predictors of EAD. Our data do not support the notion that aprotinin prevents nor attenuates PRS, EAD or mortality.

Zinc deficiency impairs wound healing of colon anastomosis in rats.

BACKGROUND: Anastomotic leakage is a relevant surgical complication. The aim of the study was to investigate the influence of a controlled preoperative zinc deficiency on the extracellular matrix composition of colon anastomosis. MATERIALS AND METHODS: Forty male Wistar rats were randomized to either a zinc deficiency group (n = 20) or a control group (n = 20). In each animal, a transverse colonic end-to-end anastomosis was performed. On postoperative day 7, the surface of the mucosal villi, expression of matrix metalloproteinases (MMP) 2, 8, 9, and 13, and both the number of proliferating cells (Ki67) and apoptotic cells, as well as the collagen types I/III ratio were analyzed. Within the anastomotic area the mesenterial region and the antimesenterial region were analyzed separately. RESULTS: In each group, one anastomotic leakage was detected. Expression of both MMP 2, 9, and 13 was significantly higher, and expression of Ki67 was significantly reduced in the zinc deficient group both mesenterial and antimesenterial. The collagen types I/III ratio was reduced in the zinc deficiency group by trend, without statistical significance neither mesenterial nor antimesenterial. Likewise, zinc deficiency affected neither the expression of MMP 8 nor the rate of apoptotic cells, respectively. Analyses of the surface of the mucosal villi revealed no significant differences comparing the groups with neither mesenterial nor antimesenterial. CONCLUSIONS: Our study constitutes the known negative effect of zinc deficiency on wound healing. Zinc deficiency significantly increased the activity of MMPs (2, 9, and 13), caused a reduced collagen type I/III ratio, and delayed cell proliferation and quality of intestinal wound healing.

Impact of gentamicin-supplemented polyvinylidenfluoride mesh materials on MMP-2 expression and tissue integration in a transgenic mice model.

PURPOSE: Reinforcement of the abdominal wall by alloplastic mesh material results in a chronic foreign body reaction which is characterized by a transcriptionally induced overexpression of the matrix metalloproteinases-2 (MMP-2). Mesh modification represents a new approach to normalize the MMP-2 expression and thereby to reduce the foreign body reaction. Because of its proven beneficial effect on tissue integration, the influence of gentamicin-supplemented polyvinylidenfluoride (PVDF) mesh materials on MMP-2 transcription and protein expression was investigated in transgenic reporter mice harboring MMP-2 regulatory sequence-1686/+423. METHODS: A PVDF mesh material was surface-modified by plasma-induced graft polymerization of acrylic acid (PVDF + PAAc). Three different gentamicin concentrations were bound to the provided active sites of the grafted mesh surfaces (2, 5, and 8 microg/mg). Seventy-five male transgenic MMP-2/LacZ CD1-tg mice harboring MMP-2 regulatory sequences -1686/+423 were randomized to five groups. Bilateral of the abdominal midline, one of the five different meshes was implanted subcutaneously in each animal. MMP-2 gene transcription and protein expression were analyzed semiquantitatively 7, 21, and 90 days after mesh implantation. The collagen type I/III ratio was analyzed by cross-polarization microscopy to determine the quality of mesh integration. RESULTS: The perifilamentary MMP-2 protein expression as well as the MMP-2 promoter activity decreased over time, whereas the collagen type I/III ratio increased up to the 90th day for all mesh modifications. The 8-microg/mg mesh material showed significantly reduced levels of MMP-2-positive stained cells when compared with the PVDF group on days 7, 21, and 90 (p = 0.008; p = 0.016; p = 0.016). In accordance, the 8-microg/mg group revealed a significant reduction of beta-galactosidase-positive stained cells at each time point in comparison with the PVDF group (p = 0.008; p = 0.047; p = 0.016). Though the type I/III collagen ratio increased over time for all mesh modifications significant differences to the PVDF mesh could only detected for 8-microg/mg group (p = 0.008; p = 0.032; p = 0.016). CONCLUSIONS: Our results show a dose-dependent effect of gentamicin. The reduced MMP-2 protein expression and transcription after mesh coating with 8 microg/mg gentamicin together with the improved collagen type I/III hint on an advanced tissue integration even in the long-term. Subsequent studies are needed to elucidate interaction of collagen and MMP-2 in chronic foreign body reaction.

Intraperitoneally applied gentamicin increases collagen content and mechanical stability of colon anastomosis in rats.

BACKGROUND: Anastomotic leakage remains a serious complication in colorectal surgery, and is being caused by a multitude of factors. Recent reports reveal changes of the extracellular matrix as risk factors as well as gentamicin as a potential agent to influence wound healing. This experimental study was initiated to investigate the influence of intraperitoneally applied gentamicin on colonic anastomotic wound healing and in particular on mechanical stability, overall collagen content and collagen type I/III ratio. MATERIALS AND METHODS: Sixty Sprague Dawley rats were randomized to one of two groups. In each animal, a standard transverse colonic end-to-end anastomosis was performed. Immediately postoperative, either 5 ml gentamicin (1 ml/kg bodyweight) or NaCl 0.9% was applied intraperitoneally. On postoperative days 3, 5, and 14, ten of the animals in each group were sacrificed. Measurements of the anastomosis bursting pressure were performed on postoperative days 3 and 5. At each explantation time, the collagen per protein ratio, the collagen types I/III ratio, and both the expression of MMP-2, -9, and Ki67 were analyzed. RESULTS: None of the animals died. None of the rats exhibited clinical evidence of anastomotic leakage. The bursting strength in the gentamicin group was significantly elevated on postoperative day 5. Both the overall collagen content and the collagen type I/III ratio in the gentamicin group were significantly increased 3, 5, and 14 days postoperatively compared to the control group. The expression of MMP-9 was significantly elevated in the gentamicin group both 3 and 5 days postoperatively. In contrast, there were no significant differences in the expression of MMP-9 14 days postoperatively. All investigated samples demonstrated positive staining for MMP-2 and Ki67 without statistically significant differences at any term, respectively. CONCLUSIONS: The present data confirm that intraperitoneally applied gentamicin is able to enhance healing and stability of colonic anastomosis due to an increase of both the overall collagen content and collagen type I/III ratio.

Adhesion formation of a polyvinylidenfluoride/polypropylene mesh for intra-abdominal placement in a rodent animal model.

BACKGROUND: Effective laparoscopic ventral herniorrhaphy mandates the use of an intraperitoneal mesh. Visceral adhesions and shrinkage of prosthetics may complicate repairs. The aim of this study was to compare adhesion formation, mesh shrinkage and tissue ingrowth after intra-abdominal placement of a novel two-component monofilament mesh structure made of polypropylene (PP) and polyvinylidenfluoride (PVDF) with current alternatives. MATERIALS AND METHODS: Forty Sprague-Dawley rats were used in this study. Mesh samples were fixed as intra-abdominal only mesh at the right lateral abdominal wall. The study groups were: PVDF+PP (polypropylene parietally and polyvinylidenfluoride viscerally), PP+Col (polypropylene with a collagenoxidized film), ePTFE (smooth surface viscerally and a textured surface parietally), and PP (a pure polypropylene mesh serving as control). The meshes were explanted after 30 days. Adhesions were scored as a percentage of explanted biomaterials' affected surface area; prosthetic shrinkage was calculated. Foreign-body reaction to mesh materials was measured by investigating the amount of inflammatory infiltrate and fibrotic tissue formation. RESULTS: In terms of adhesion score, the pure PP mesh showed the highest values followed by the ePTFE, PVDF+PP, and PP+Col meshes. Quantitative assessment of adhesion area revealed a significantly higher value of the pure PP mesh sample (62.0 +/- 22.1%) compared with the PP+Col (26.8 +/- 12.1%) and the PVDF+PP mesh (34.6 +/- 8.2%). Percentage of shrinkage showed a significantly higher value of the ePTFE mesh (52.4 +/- 13.9%) compared with all other mesh modifications (PP+Col 19.8 +/- 13.9%, PVDF+PP 19.9 +/- 7.0%, and PP 26.8 +/- 9.5%). Inflammatory infiltrate was significantly reduced in the PVDF+PP mesh group compared with all other mesh samples. CONCLUSION: The use of the novel two-component monofilament mesh structure made of polypropylene and polyvinylidenfluoride was found to be favorable regarding adhesion formation and mesh shrinkage compared to conventional mesh materials used for intra-abdominal placement.

Risk factors for early recurrence after inguinal hernia repair.

BACKGROUND: Family history, male gender and age are significant risk factors for inguinal hernia disease. Family history provides evidence for a genetic trait and could explain early recurrence after inguinal hernia repair despite technical advance at least in a subgroup of patients. This study evaluates if age and family history can be identified as risk factors for early recurrence after primary hernia repair. METHODS: We performed an observational cohort study for 75 patients having at least two recurrent hernias. The impact of age, gender and family history on the onset of primary hernias, age at first recurrence and recurrence rates was investigated. RESULTS: 44% (33/75) of recurrent hernia patients had a family history and primary as well as recurrent hernias occurred significantly earlier in this group (p = 0.04). The older the patients were at onset the earlier they got a recurrent hernia. Smoking could be identified as on additional risk factor for early onset of hernia disease but not for hernia recurrence. CONCLUSION: Our data reveal an increased incidence of family history for recurrent hernia patients when compared with primary hernia patients. Patients with a family history have their primary hernias as well as their recurrence at younger age then patients without a family history. Though recurrent hernia has to be regarded as a disease caused by multiple factors, a family history may be considered as a criterion to identify the risk for recurrence before the primary operation.

Morphology, quality, and composition in mature human peritoneal adhesions.

BACKGROUND AND AIM: Peritoneal adhesions are caused by intra-abdominal surgery and can lead to relevant complications. Adhesions are supposed to consist of avascular scar tissue. The aim of the present study was to analyze whether mature postsurgical adhesions even after years still reveal a dynamic remodeling process. MATERIALS AND METHODS: In a prospective analysis, we investigated tissue specimen of peritoneal adhesions in 40 patients after abdominal surgery. Expression of five parameters representing wound healing and remodeling were examined (MMP-2, Ki-67, apoptosis, collagen/protein ratio, and collagen type I/III ratio). RESULTS: Gender, age, and the number of previous operations had no impact on the parameters measured. Adhesion specimens were cell rich, containing mononuclear round cells, fibroblasts, adipose cells, and vascular endothelial cells. There was a positive expression of MMP-2 and apoptosis, whereas Ki-67 was marginal irrespective of adhesion maturity or quality. Adhesions classified as dense showed a significant increase in total collagen (118.2 +/- 4.9 microg/mg) and collagen type I/III ratios (3.9 +/- 0.2), whereas there were no significant differences regarding the adhesion maturity. CONCLUSION: The distinct composition of cellular components as well as of extracellular matrix proteins may reflect an interactive cross-talk between adhesion- and stroma-derived cells even in mature adhesions. Our findings support the hypothesis that the disabilities of appropriate repair of the peritoneal surface leading to persistent adhesions are a consequence of a permanent process of disturbed remodeling.

Biomechanical analyses of overlap and mesh dislocation in an incisional hernia model in vitro.

BACKGROUND: Incisional hernia repair is one of the most common surgical complications. Despite the introduction of mesh techniques of repair, recurrences are still prevalent. The aim of the current study was to evaluate the dependence of mesh dislocation on defect size, facial overlap, mesh-position, and orientation of the mesh in cases of anisotropic stretchability. METHODS: An in vitro incisional hernia model was used, which consisted of a pressure chamber, an elastic silicone pad representing the peritoneal sac, and a silicone mat with bovine muscle tissue representing the abdominal wall. Intrinsic pressure (up to 200 mm Hg) was generated within the pressure chamber by continuous inflation with CO(2). A slit-like or flap-like defect was created in the silicone mat to simulate small or large hernia defects, respectively. The implanted mesh was arranged in both onlay and sublay configurations. A large pore polypropylene mesh with significant anisotropic stretchability was investigated, whereas overlaps of 2, 3, and 4 cm were applied. RESULTS: Despite the application of pressures up to 200 mm Hg, no mesh ruptures occurred. In the slit-like defect model, the minimal overlap required to prevent dislocation at 200 mm Hg was 3 cm using the sublay technique provided that the mesh was positioned with its most stretchable axis parallel to the largest slit dehiscence. Perpendicular rotation of the mesh resulted in dislocation at 160 mm Hg, despite using an overlap of 3 cm. Mesh reinforcement showed less stability in both the onlay position and the flap-like defect. CONCLUSION: An overlap of 3 cm is sufficient to prevent early mesh dislocation. Meshes with anisotropic stretchability should be orientated with the most stretchable axis in the direction of least overlap.

Hernia fibroblasts lack beta-estradiol-induced alterations of collagen gene expression.

BACKGROUND: Estrogens are reported to increase type I and type III collagen deposition and to regulate Metalloproteinase 2 (MMP-2) expression. These proteins are reported to be dysregulated in incisional hernia formation resulting in a significantly decreased type I to III ratio. We aimed to evaluate the beta-estradiol mediated regulation of type I and type III collagen genes as well as MMP-2 gene expression in fibroblasts derived from patients with or without history of recurrent incisional hernia disease. We compared primary fibroblast cultures from male/female subjects without/without incisional hernia disease. RESULTS: Incisional hernia fibroblasts (IHFs) revealed a decreased type I/III collagen mRNA ratio. Whereas fibroblasts from healthy female donors responded to beta-estradiol, type I and type III gene transcription is not affected in fibroblasts from males or affected females. Furthermore beta-estradiol had no influence on the impaired type I to III collagen ratio in fibroblasts from recurrent hernia patients. CONCLUSION: Our results suggest that beta-estradiol does not restore the imbaired balance of type I/III collagen in incisional hernia fibroblasts. Furthermore, the individual was identified as an independent factor for the beta-estradiol induced alterations of collagen gene expression. The observation of gender specific beta-estradiol-dependent changes of collagen gene expression in vitro is of significance for future studies of cellular response.

Is there a risk of infertility after inguinal mesh repair? Experimental studies in the pig and the rabbit.

The implantation of a non-absorbable polypropylene mesh during hernia repair causes chronic foreign body reaction involving the surrounding tissue. In case of inguinal hernia repair using mesh techniques, the spermatic cord is potentially affected by this chronic inflammatory tissue remodeling. This effect has been investigated using standardized animal models (pig and rabbit). Fifteen adult male pigs underwent transinguinal preperitoneal implantation of a polypropylene mesh. The contralateral side with a Shouldice repair served as control. After 7, 14, 21, 28, and 35 days, three animals were sacrificed. The spermatic cords were resected and analyzed histologically. In a second experiment Lichtenstein repair using the same polypropylene mesh and Shouldice repair on the contralateral side was done in eight chinchilla rabbits. Three animals served as controls. Three months after operation, the analysis included testicular size, testicular temperature, and testicular and spermatic cord perfusion. We added histological evaluation of the foreign body reaction and the spermatogenesis using the Johnsen score. In the pig, we observed a certain foreign body reaction with diffuse infiltrating inflammatory cells after mesh implantation. Venous thrombosis of the spermatic veins occurred in five of 15 cases. One animal presented focal fibrinoid necrosis of the deferent duct wall. The side of Shouldice repair showed only minor postoperative changes. In the rabbit, we also observed a typical foreign body reaction at the interface between mesh and surrounding tissue, which was not detectable after Shouldice repair. The mesh repair led to a decrease of arterial perfusion, testicular temperature, and the rate of seminiferus tubules with regular spermatogenesis classified as Johnsen 10 (Lichtenstein: 48.1%, Shouldice: 63.8%, controls: 65.8%). Testicular volume increased about 10% after each operation. The implantation of a polypropylene mesh in the inguinal region induces major response of the structures of the spermatic cord. This may have an influence also on spermatogenesis. Due to this a strict indication for implantation of a prosthetic mesh during inguinal hernia repair is recommended.