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.

[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.

Bypass during Liver Transplantation: Anachronism or Revival? Liver Transplantation Using a Combined Venovenous/Portal Venous Bypass-Experiences with 163 Liver Transplants in a Newly Established Liver Transplantation Program.

Introduction. The venovenous/portal venous (VVP) bypass technique has generally become obsolete in liver transplantation (LT) today. We evaluated our experience with 163 consecutive LTs that used a VVP bypass. Patients and Methods. The liver transplant program was started in our center in 2010. LTs were performed using an extracorporal bypass device. Results. Mean operative time was 269 minutes and warm ischemic time 43 minutes. The median number of transfusion of packed cells and plasma was 7 and 14. There was no intraoperative death, and the 30-day mortality was 3%. Severe bypass-induced complications did not occur. Discussion. The introduction of a new LT program requires maximum safety measures for all of the parties involved. Both surgical and anaesthesiological management (reperfusion) can be controlled very reliably using a VVP bypass device. Particularly when using marginal grafts, this approach helps to minimise both surgical and anaesthesiological complications in terms of less volume overload, less use of vasopressive drugs, less myocardial injury, and better peripheral blood circulation. Conclusion. Based on our experiences while establishing a new liver transplantation program, we advocate the reappraisal of the extracorporeal VVP bypass.

Risk factors for coagulopathy after liver resection.

STUDY OBJECTIVE: To identify risk factors for coagulopathy in patients undergoing liver resection. DESIGN: A retrospective cohort study. SETTING: Patients who underwent liver resection at a university hospital between April 2010 and May 2011 were evaluated within seven days after surgery. PATIENTS: One hundred forty-seven patients were assessed for eligibility. Thirty needed to be excluded because of incomplete data (23) or a preexisting coagulopathy (7). MEASUREMENTS: Coagulopathy was defined as 1 or more of the following events: international normalized ratio ≥1.4, platelet count <80,000/µL, and partial thromboplastin time >38 seconds. Related to the time course and coagulation profile thresholds, 3 different groups could be distinguished: no coagulopathy, temporary coagulopathy, and persistent coagulopathy. MAIN RESULTS: Seventy-seven patients (65.8%) had no coagulopathy, whereas 33 (28.2%) developed temporary coagulopathy and 7 (6%) developed persistent coagulopathy until day 7. Preoperative international normalized ratio (P = .001), postoperative peak lactate levels (P = .012), and resected liver weight (P = .005) were identified as independent predictors. Preoperative liver transaminases and transfusion volumes of red blood cells and fresh frozen plasma were significantly higher in patients with persistent coagulopathy. CONCLUSIONS: Epidural anesthesia is feasible in patients scheduled for liver resection. Caution should be observed for patients with extended resection (≥3 segments) and increased postoperative lactate. In patients with preexisting liver disease, epidural catheters should be avoided.

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.

Fulminant Epstein-Barr virus - infectious mononucleosis in an adult with liver failure, splenic rupture, and spontaneous esophageal bleeding with ensuing esophageal necrosis: a case report.

INTRODUCTION: Infectious mononucleosis is a clinical syndrome most commonly associated with primary Epstein-Barr virus infection. The majority of patients with infectious mononucleosis recovers without apparent sequelae. However, infectious mononucleosis may be associated with several acute complications. In this report we present a rare case of esophageal rupture that has never been described in the literature before. CASE PRESENTATION: We present the case of an 18-year-old Caucasian man affected by severe infectious mononucleosis complicated by fulminant hepatic failure, splenic rupture and esophageal necrosis. CONCLUSIONS: Although primary Epstein-Barr virus infection is rarely fatal, fulminant infection may occur - in this case leading to hepatic failure, splenic rupture and esophageal necrosis, subsequently making several surgical interventions necessary. We show here that infectious mononucleosis is not only a strictly medical condition, but can also lead to severe surgical complications.

Initial diagnosis of Wegener's granulomatosis mimicking severe ulcerative colitis: a case report.

INTRODUCTION: We describe the case of a woman with an unusual presentation of Wegener's granulomatosis. CASE PRESENTATION: A 20-year old Caucasian woman presented with the principal feature of a pancolonic, superficial microulceration mimicking severe ulcerative colitis. Our patient was refractory to therapy and had persisting signs of septic shock as well as being at risk of perforation, so we performed a subtotal colectomy and a cholecystectomy due to the incipient necrosis of her gallbladder. Histologic analysis of her colon showed multiple superficial microulcera of the mucosa, lamina propria mucosae and, to a lesser extent, the lamina submucosa. The medium-sized arteries and arterioles of her entire colon, appendix and gallbladder showed acute vasculitic changes with fibrinoid necrosis of the walls and diffuse infiltration with neutrophil granulocytes, accompanied by a strong perivascular histiocyte-rich and partially granulomatous reaction. These findings strongly suggested an autoimmune multisystem disease like Wegener's granulomatosis or microscopic polyangiitis. A diagnosis of Wegener's granulomatosis was confirmed by the results of serologic antibody tests: her cytoplasmic antineutrophil cytoplasmic antibody titer was considerably elevated at 1:2560 specific for subclass proteinase 3 (>200kU/L). After the histopathological diagnosis and serological tests, immunosuppression with high doses of corticosteroids and plasmapheresis was started. CONCLUSION: In critically ill patients with severe, therapy-refractory ulcerative colitis, Wegener´s granulomatosis should be considered and serologic antibody testing should be performed.

Extended distal pancreatectomy with en bloc resection of the celiac axis for locally advanced pancreatic cancer: a case report and review of the literature.

Due to a lack of early symptoms, pancreatic cancers of the body and tail are discovered mostly at advanced stages. These locally advanced cancers often involve the celiac axis or the common hepatic artery and are therefore declared unresectable. The extended distal pancreatectomy with en bloc resection of the celiac artery may offer a chance of complete resection. We present the case of a 48-year-old female with pancreatic body cancer invading the celiac axis. The patient underwent laparoscopy to exclude hepatic and peritoneal metastasis. Subsequently, a selective embolization of the common hepatic artery was performed to enlarge arterial flow to the hepatobiliary system and the stomach via the pancreatoduodenal arcades from the superior mesenteric artery. Fifteen days after embolization, the extended distal pancreatectomy with splenectomy and en bloc resection of the celiac axis was carried out. The postoperative course was uneventful, and complete tumor resection was achieved. This case report and a review of the literature show the feasibility and safety of the extended distal pancreatectomy with en bloc resection of the celiac axis. A preoperative embolization of the celiac axis may avoid ischemia-related complications of the stomach or the liver.

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.

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.

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.

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 prosthetic meshes in abdominal surgery.

Surgical meshes today represent a group of implants mainly used for hernia repair. Modern hernia surgery is no longer imaginable without the application of these special biomaterials leading to millions of implantations each year worldwide. Because clinical trials are insufficient to evaluate the distinct effects of modified mesh materials in regard to tissue biocompatibility and functionality, a basic understanding of the physicochemical properties of mesh materials, as well as the underlying cause for hernia formation, is essential for a rational selection of the most appropriate device. The most important properties of meshes were found to be the type of filament, tensile strength, and experimental data, which indicate that particularly the mesh's porosity is of outstanding importance.

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.

Surgical technique for gastroesophageal reflux disease.

AIMS: Laparoscopic fundoplication is the standard surgical therapy for managing gastroesophageal reflux disease. According to the pre-existing esophageal motility of the patient, tailoring antireflux surgery has been proposed in order to avoid postoperative dysphagia. Thus, the aim of this study is to evaluate the long-term results following this tailored concept. METHODS: One-hundred sixty patients were included in this prospective study. A 360° Nissen fundoplication (NF) was performed on n = 127 patients with a normal esophageal peristalsis, whereas a 270° Toupet fundoplication (TF) was conducted on n = 33 patients having an esophageal motility disorder. Before surgery, all the patients were subjected to pH-metry, manometry, gastroscopy, and they had to respond to a standardized questionnaire. Postoperatively, pH-metry, and manometry were performed. In addition to the questionnaire, side effects and complications were evaluated. RESULTS: The NF cohort and the TF cohort were each followed up for an average of 39 ± 13 months and 43 ± 12 months, respectively. Dysphagia was significantly reduced after NF (p = .033). The TF, however, decreased the intensity but not the incidence of dysphagia (p = .884). Heartburn was significantly diminished in both cohorts. The DeMeester score was significantly reduced after NF, whereas it was not significantly reduced following TF with a still evident, pathological acid reflux occurring postoperatively. CONCLUSION: Our data indicate that tailoring antireflux surgery to the esophageal motility of the patient seems unnecessary. In summary, technical surgical aspects appear to be more important for clinical outcome.

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.