Stapled versus hand-sewn anastomoses after bowel resection in patients with crohn disease.

BACKGROUND: Anastomosis configuration is an essential step in treatment to restore continuity of the gastrointestinal tract following bowel resection in patients with Crohn's disease (CD). However, the association between anastomotic type and surgical outcome remains controversial. This retrospective study aimed to compare early postoperative complications and surgical outcome between stapler and handsewn anastomosis after bowel resection in Crohn's disease. METHODS: Between 2001 and 2018, a total of 339 CD patients underwent bowel resection with anastomosis. Patient characteristics, intraoperative data, early postoperative complications, and outcomes were analyzed and compared between two groups of patients. Group 1 consisted of patients with stapler anastomosis and group 2 with handsewn anastomosis. RESULTS: No significant difference was found in the incidence of postoperative surgical complications between the stapler and handsewn anastomosis groups (25% versus 24.4%, p = 1.000). Reoperation for complications and postoperative hospital stay were similar between the two groups. CONCLUSION: Our analysis showed that there were no differences in anastomotic leak, nor postoperative complications, mortality, reoperation for operative complications, or postoperative hospital stay between the stapler anastomosis and handsewn anastomosis groups.

Danger Zones of the Gluteal Anatomy: Improving the Safety Profile of the Gluteal Fat Grafting.

INTRODUCTION: Knowledge of the vascular anatomy is critical to performing safe gluteal surgery. To date, only the course of the main blood vessels within the muscles has been outlined. These findings are based on MRI and CTA images that do not conform to a topographically standardized and normalized probability distribution. OBJECTIVES: The aim of this study was to develop a three-dimensional mapping of the gluteal zones of high vascular density in relation to anatomical landmarks. MATERIALS AND METHODS: This single-center retrospective cohort analysis comprised all consecutive patients who underwent cone-beam computed tomography (CBCT) scans between January 2016 and October 2021. The location of blood vessels in the gluteal region was allometrically normalized in relation to anatomical landmarks. Moreover, the caliber and area of the blood vessels were assessed. RESULTS: CBCT scans of 32 patients with an average age of 64 ± 12 years (range 34-87 years) were included. Fifty-three percent were female. The median [IQR] caliber of the intramuscular gluteal vessels was 1.47 [1.15-1.88] mm, significantly greater than that of the subcutaneous vessels 1.09 [0.72-1.44] mm (p < 0.001). Vascular density was higher intramuscularly, as 4.5% of the area of the muscle was occupied by blood vessels, as opposed to 0.3% in the adipose tissue. CONCLUSION: The analysis of the CBCT scans showed a higher vascular density and larger vessels intramuscularly. We, therefore, recommend the injection of autologous fat merely to the subcutaneous plane. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effect of immunosuppressive medication on postoperative complications following abdominal surgery in Crohn's disease patients.

BACKGROUND: Immunosuppressants represent an effective pharmacological treatment for the remission and management of Crohn's disease (CD); however, it has not been well-defined if these medications are associated with an increased incidence of postoperative complications after intestinal surgery. This retrospective study evaluated the association between immunosuppressive treatment and complications following bowel resection in patients with CD. METHODS: A total of 426 patients with CD who underwent abdominal surgery between 2001 and 2018 were included in the study. The participants were divided into two groups. In the first group, patients were under immunosuppressive treatment at the time of surgical resection, while in the second group, patients had never received pharmacological therapy for CD before surgery. RESULTS: No statistically significant difference was found in the incidence of postoperative complications between the two groups. Double or triple immunosuppressive therapy was not associated with increased complications compared to monotherapy or no pharmacological treatment. Preoperative risk factors such as hypoalbuminemia, abscess, fistula, intestinal perforation, long duration of symptoms, and the intraoperative performance of more than one anastomosis were related to increased rates of postoperative complications. Factors affecting the occurrence of postoperative complications in the univariate analysis were included in the multivariate analysis using a stepwise logistic regression model, and these factors were also related to increased rates of postoperative surgical complications. CONCLUSION: Immunosuppressive therapy was not associated with increased rates of postoperative complications following bowel resection in patients with CD.

Volume-Function Analysis (LiMAx Test) in Patients with HCC and Cirrhosis Undergoing TACE-A Feasibility Study.

BACKGROUND: Transarterial chemoembolization (TACE) is an important therapy for hepatocellular carcinoma (HCC) in cirrhosis. In particular in advanced cirrhosis, post-TACE hepatic failure liver (PTHF) failure may develop. Currently, there is no standardization for the periinterventional risk assessment. The liver maximum capacity (LiMAx) test assesses the functional liver capacity, but has not been investigated in this setting. AIMS: The aim of this study was to prospectively evaluate periinterventional LiMAx and CT volumetry measurements in patients with cirrhosis and HCC undergoing repetitive TACE. METHODS: From 06/2016 to 11/2017, eleven patients with HCC and cirrhosis undergoing TACE were included. LiMAx measurements (n = 42) were conducted before and after each TACE. Laboratory parameters were correlated with the volume-function data. RESULTS: The median LiMAx levels before (276 ± 166 µg/kg/h) were slightly reduced after TACE (251 ± 122 µg/kg/h; p = 0.08). This corresponded to a median drop of 7.1%. Notably, there was a significant correlation between LiMAx levels before TACE and bilirubin (but not albumin nor albumin-bilirubin [ALBI] score) increase after TACE (p = 0.02, k = 0.56). Furthermore, a significantly higher increase in bilirubin in patients with LiMAx ≤ 150 µg/kg/h was observed (p = 0.011). LiMAx levels at different time points in single patients were similar (p = 0.2). CONCLUSION: In our prospective pilot study in patients with HCC and cirrhosis undergoing multiple TACE, robust and reliable LiMAx measurements were demonstrated. Lower LiMAx levels before TACE were associated with surrogate markers (bilirubin) of liver failure after TACE. Specific subgroups at high risk of PTHF should be investigated. This might facilitate the future development of strategies to prevent occurrence of PTHF.

Predictive Power of Liver Maximum Function Capacity Test in Transjugular Intrahepatic Portosystemic Shunt Patients: A Pilot Study.

BACKGROUND: Transjugular intrahepatic shunt (TIPSS) is placed in patients with variceal bleeding, refractory ascites, and for other indications. Postprocedural liver function-associated complications (LFAC), including hepatic encephalopathy (HE) and liver failure, represent a major setback. Current methods to predict complications are insufficient. OBJECTIVES: We investigated in a pilot study of patients prior TIPSS placement whether the risk of LFAC correlates with the functional reserve of the liver, as assessed by liver maximum function capacity (LiMAx) test. METHODS: Prospectively we included patients prior TIPSS placement between June 2016 and November 2017 at Saarland University Medical Center. LiMAx was conducted before and after TIPSS placement. Patients with HE prior TIPSS, as well as other factors predisposing to HE, including concomitant sedative drugs, current bacterial infections and sepsis, were excluded. Overt HE (OHE), LiMAx, and laboratory values were assessed before and after TIPSS placement. Data were analyzed in multivariate regression and AUROC models. RESULTS: Mean age was 60 ± 8 years. Patients (n = 20) were mainly men (65%), and presented predominantly with Child-Pugh class B (90%). Indications for TIPSS were most commonly refractory ascites or recurrent variceal bleeding. In total, 40% of the patients developed LFAC after TIPSS placement. Expectedly, LiMAx decreased and serum bilirubin increased after TIPSS. LiMAx drop ≥20% was the only parameter predicting the development of LFAC after TIPSS in multivariate regression and AUROC analysis. CONCLUSIONS: In multivariate regression models and AUROC analysis, a drop in LiMAx predicted the development of LFAC after TIPSS placement. Additional larger studies assessing OHE and early liver failure separately are warranted.

Intra-arterial EmboCept S® and DC Bead® effectively inhibit tumor growth of colorectal rat liver metastases.

BACKGROUND: Intra-arterial therapy with embolics is established for the treatment of malignancies of the liver. However, there are no studies comparing the different effects of various embolics used in clinical practice. Herein, we analyzed the effect of 3 different embolics on tumor growth in a rat model of colorectal liver metastases. METHODS: Eight days after subcapsular implantation of 5 × 105 colorectal cancer cells (CC531) in the left liver lobe of WAG/Rij rats were randomized into 4 groups (n = 8) and underwent intra-arterial hepatic therapy. Animals received either EmboCept S®, DC Bead® or Lipiodol® Ultra-Fluid. Animals of the control group received a comparable amount of saline. Tumor growth was measured on day 8 and 11 using a three-dimensional 40 MHz ultrasound device. On day 11 tumor and liver tissue were removed for histological and immunohistochemical analyses. RESULTS: On day 11 animals of the control group showed a tumor growth of ~ 60% compared to day 8. Application of Lipiodol Ultra-Fluid® did not significantly influence tumor growth (~ 40%). In contrast, treatment with EmboCept S® or DC Bead® completely inhibited tumor growth. Of interest, application of EmboCept S® did not only completely inhibit tumor growth but even decreased tumor size. Immunohistochemical analysis showed a significant increase of necrotic areas within the tumors after application of EmboCept S® and DC Bead® compared to Lipiodol® Ultra-Fluid. CONCLUSION: The present study demonstrates that an intra-arterial therapy with EmboCept S® and DC Bead®, but not Lipiodol® Ultra-Fluid, results in a complete inhibition of rat colorectal liver metastatic growth.

MicroRNA-496 and Mechanistic Target of Rapamycin Expression are Associated with Type 2 Diabetes Mellitus and Obesity in Elderly People.

BACKGROUND: Mechanistic target of rapamycin (mTOR) regulates lipid and glucose metabolism thus playing a key role in metabolic diseases like type 2 diabetes mellitus (T2DM). Recently, we demonstrated a functional interaction of microRNA-496 (miR-496) with mTOR and its impact on the regulation of human ageing. OBJECTIVES: As T2DM is most prevalent in older adults, we hypothesized that miR-496 may also have an impact on mTOR regulation in T2DM. METHODS: Based on real-time PCR and enzyme-linked immunosorbent assay, mTOR gene and protein expression as well as miR-496 expression were monitored in peripheral blood mononuclear cells (PBMC) from T2DM patients (median age: 71) and healthy age- and BMI matched controls (median age: 69). -Results: We demonstrated significant upregulation of phospho-mTOR and P70S6 Kinase (P70S6K) levels and significant downregulation of miR-496 in PBMC from elderly T2DM patients in comparison to a BMI and age-matched control cohort. Moreover, significant upregulation of phospho-mTOR protein and significant downregulation of miR-496 were observed in advanced stages of obesity. CONCLUSIONS: BMI-dependent upregulation of mTOR and the inverse expression profile of miR-496 observed in elderly T2DM patients suggest a correlation with T2DM. Hence, our results indicate a potential association of miR-496 with mTOR expression in elderly T2DM patients and obesity. Since phosphorylation of P70S6K was also elevated in T2DM patients, we conclude that mTOR signaling through TORC1 may be affected in the regulation of T2DM.

Benefits of Robotic Camera Assistance in Minimally Invasive Bariatric Procedures: Prospective Clinical Trial Using a Joystick-Guided Camera-Holder.

BACKGROUND: While minimally invasive surgery is a growing sector in medicine, camera assistance remains a problem. Especially in bariatric surgery, the assistant holding the camera faces certain challenges. Furthermore, unless the surgeon controls the camera movement themselves, they will be challenged by an unstable image. The aim of this study was to investigate the benefits of a robotic camera assistant (SoloAssist®, AKTORmed™ GmbH, Barbing, Germany) in bariatric surgery. PATIENTS AND METHODS: Three hundred thirty one consecutive laparoscopic bariatric procedures were performed with the assistance of a camera robot, including Roux-en-Y gastric bypass, laparoscopic gastric banding, sleeve gastrectomy, and gastroplication. Failures and aborts were documented and 6 surgeons were interviewed regarding their experiences using a questionnaire. RESULTS: In 18 of 331 procedures, robotic assistance was aborted and the procedure was continued manually, mostly because of a need for frequent changes of position in narrow spaces and adverse angles. Two short circuits, 4 joystick faliures and one malfunction of the control unit were reported. All of the surgeons preferred robotic to human assistance, mostly because of a steady image and the capacity for self-control. DISCUSSION: The SoloAssist® is a reliable system for minimal invasive procedures, especially in bariatric surgery. It provides more comfortable conditions for the surgeon and their assistant by freeing one hand for other purposes. Even in narrow spaces (e.g., between a voluminous stomach and adipose liver), the robot guarantees a steady image. Slight movements of the camera can be precisely controlled, which leads to increased comfort for the surgeon.

Partial pancreatoduodenectomy versus duodenum-preserving pancreatic head resection in chronic pancreatitis: the multicentre, randomised, controlled, double-blind ChroPac trial.

BACKGROUND: There is substantial uncertainty regarding the optimal surgical treatment for chronic pancreatitis. Short-term outcomes have been found to be better after duodenum-preserving pancreatic head resection (DPPHR) than after partial pancreatoduodenectomy. Therefore, we designed the multicentre ChroPac trial to investigate the long-term outcomes of patients with chronic pancreatitis within 24 months after surgery. METHODS: This randomised, controlled, double-blind, parallel-group, superiority trial was done in 18 hospitals across Europe. Patients with chronic pancreatitis who were planned for elective surgical treatment were randomly assigned to DPPHR or partial pancreatoduodenectomy with a central web-based randomisation tool. The primary endpoint was mean quality of life within 24 months after surgery, measured with the physical functioning scale of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. Primary analysis included all patients who underwent one of the assigned procedures; safety analysis included all patients who underwent surgical intervention (categorised into groups as treated). Patients and outcome assessors were masked to group assignment. The trial was registered, ISRCTN38973832. Recruitment was completed on Sept 3, 2013. FINDINGS: Between Sept 10, 2009, and Sept 3, 2013, 250 patients were randomly assigned to DPPHR (n=125) or partial pancreatoduodenectomy (n=125), of whom 226 patients (115 in the DPPHR group and 111 in the partial pancreatoduodenectomy group) were analysed. No difference in quality of life was seen between the groups within 24 months after surgery (75·3 [SD 16·4] for partial pancreatoduodenectomy vs 73·0 [16·4] for DPPHR; mean difference -2·3, 95% CI -6·6 to 2·0; p=0·284). The incidence and severity of serious adverse events did not differ between the groups. 70 (64%) of 109 patients in the DPPHR group and 61 (52%) of 117 patients in the partial pancreatoduodenectomy group had at least one serious adverse event, with the most common being reoperations (for reasons other than chronic pancreatitis), gastrointestinal problems, and other surgical morbidity. INTERPRETATION: No differences in quality of life after surgery for chronic pancreatitis were seen between the interventions. Results from single-centre trials showing superiority for DPPHR were not confirmed in the multicentre setting. FUNDING: German Research Foundation (DFG).

A Variant of COL3A1 (rs3134646) Is Associated With Risk of Developing Diverticulosis in White Men.

BACKGROUND: Colonic diverticulosis is one of the most common gastroenterological disorders. Although diverticulosis is typically benign, many individuals develop diverticulitis or other aspects of diverticular disease. Diverticulosis is thought to stem from a complex interaction of environmental, dietary, and genetic factors; however, the contributing genetic factors remain unknown. OBJECTIVE: The aim of our present study was to determine the role of genetic variants within genes encoding for collagens of the connective tissue in diverticulosis. DESIGN: This was a transsectional genetic association study. SETTINGS: This study was conducted at three tertiary referral centers in Germany and Lithuania. PATIENTS: Single-nucleotide polymorphisms in COL3A1 (rs3134646, rs1800255) and COL1A1 (rs1800012) were genotyped in 422 patients with diverticulosis and 285 controls of white descent by using TaqMan assays. MAIN OUTCOME MEASURES: The association of colonoscopy-proven diverticulosis with genetic polymorphisms with herniations was assessed in multivariate models. RESULTS: The rs3134646, rs1800255, and rs1800012 variants were significantly associated with the risk of developing diverticulosis in the univariate model; however, these associations were not significant in the multivariate logistic regression analysis including additional nongenetic variables. When selectively analyzing sexes, the genotype AA (AA) in rs3134646 remained significantly associated with diverticulosis in men (OR, 1.82; 95% CI, 1.04-3.20; p = 0.04). LIMITATIONS: Because a candidate approach was used, additional relevant variants could be missed. Within our cohort of patients with diverticulosis, only a small proportion had diverticular disease and thus, we could not examine the variants in these subgroups. Functional studies, including the analysis of the involved collagens, are also warranted. CONCLUSIONS: Our study shows that a variant of COL3A1 (rs3134646) is associated with the risk of developing colonic diverticulosis in white men, whereas rs1800255 (COL3A1) and rs1800012 (COL1A1) were not associated with this condition after adjusting for confounding factors. Our data provide novel valuable insights in the genetic susceptibility to diverticulosis. See Video Abstract at http://links.lww.com/DCR/A504.

Acute appendicitis in children: can surgery be postponed? Short-term results in a cohort of 225 children.

PURPOSE: To our knowledge, there is no German study, which has examined the relationship between a postponement of surgery (from emergency service to standard working time) and the corresponding risk of postoperative complications in children and adolescents with acute appendicitis. The aim of this study is to examine if surgery of acute appendicitis in childhood can be postponed from night shift to the next working day without negative effects for the patient. METHODS: In a retrospective analysis (September 2001 to June 2007), the files of 225 paediatric surgical patients with acute appendicitis have been analysed concerning history, histology, course of treatment and development of complications. The cohort was divided into groups by their histology (common, "A", complicated appendicitis, "B") and by the median time (10 h) from admission to surgery (immediate, "C", delayed surgery, "D"). These groups have been analysed and compared. RESULTS: Groups A and B did not differ concerning time to admittance (p = 0.922). Seven patients developed complications (n = 7/225, 3.1%). Six complications were seen in group C (n = 6/113, 5.3%) compared to 1 in group D (n = 1/112, 0.9%), the difference was not significant (p = 0.119). None of the patients of group B developed complications after delayed surgery. Median follow-up was 10 days (IQR 7-15). CONCLUSIONS: In view of the development of complications, there was no evidence that the time between inpatient admission and surgery had any impact on the postoperative result. Thus, there is usually no need to perform surgery in common appendicitis during night shift.

A novel human gastric primary cell culture system for modelling Helicobacter pylori infection in vitro.

BACKGROUND AND AIMS: Helicobacter pylori is the causative agent of gastric diseases and the main risk factor in the development of gastric adenocarcinoma. In vitro studies with this bacterial pathogen largely rely on the use of transformed cell lines as infection model. However, this approach is intrinsically artificial and especially inappropriate when it comes to investigating the mechanisms of cancerogenesis. Moreover, common cell lines are often defective in crucial signalling pathways relevant to infection and cancer. A long-lived primary cell system would be preferable in order to better approximate the human in vivo situation. METHODS: Gastric glands were isolated from healthy human stomach tissue and grown in Matrigel containing media supplemented with various growth factors, developmental regulators and apoptosis inhibitors to generate long-lasting normal epithelial cell cultures. RESULTS: Culture conditions were developed which support the formation and quasi-indefinite growth of three dimensional (3D) spheroids derived from various sites of the human stomach. Spheroids could be differentiated to gastric organoids after withdrawal of Wnt3A and R-spondin1 from the medium. The 3D cultures exhibit typical morphological features of human stomach tissue. Transfer of sheared spheroids into 2D culture led to the formation of dense planar cultures of polarised epithelial cells serving as a suitable in vitro model of H. pylori infection. CONCLUSIONS: A robust and quasi-immortal 3D organoid model has been established, which is considered instrumental for future research aimed to understand the underlying mechanisms of infection, mucosal immunity and cancer of the human stomach.

Perigraft vascularization and incorporation of implanted Dacron prostheses are affected by rifampicin coating.

BACKGROUND: Prosthetic vascular grafts are increasingly implanted to replace damaged arteries. However, their microbial contamination is highly problematic and often results in devastating clinical complications. To reduce the risk of infection, Dacron grafts may be coated with rifampicin. In this experimental study we analyzed whether this coating affects the early tissue incorporation of the grafts. METHODS: Saline- and rifampicin-coated Dacron (Dacron-Rifamp) grafts were implanted into dorsal skinfold chambers of C57BL/6 mice (n = 8 per group) to study vascularization, inflammation, cell proliferation, and apoptosis at the implantation site using repetitive intravital fluorescence microscopy and immunohistochemistry over an observation period of 14 days. RESULTS: Implanted Dacron-Rifamp grafts exhibited a impaired vascularization, indicated by a significantly lower functional capillary density (85 ± 1 cm/cm2) compared with controls (113 ± 1 cm/cm2; P < .05). This was associated with a reduced number of Ki-67-positive proliferating cells (9.4% ± 1.1% vs 13.5 ± 0.4%; P < .05) and an increased number of cleaved caspase-3-positive apoptotic cells (2.7% ± 0.3% vs 1.3% ± 0.3%; P < .05) in the newly developing granulation tissue surrounding the implants. In addition, the neutrophilic (652 ± 84 mm2 vs 934 ± 117 mm2; P = .06), lymphatic (26 ± 6 mm2 vs 39 ± 9 mm2; P = .24) and macrophage response (177 ± 42 mm2 vs 233 ± 86 mm2; P = .57) was decreased by trend in the group with Dacron-Rifamp grafts. CONCLUSIONS: Our novel findings show that early perigraft vascularization and incorporation of implanted Dacron prostheses are affected by the rifampicin coating. Because rapid graft vascularization and incorporation are thought to reduce the risk of infection, the use of Dacron-Rifamp Dacron grafts for antibacterial prophylaxis should be reconsidered particularly in cases of elective arterial reconstruction in a noninfected environment.

Short-term postoperative outcomes of lymphadenectomy for cholangiocarcinoma, hepatocellular carcinoma and colorectal liver metastases in the modern era of liver surgery: Insights from the StuDoQ|Liver registry.

INTRODUCTION: The clinical role of lymphadenectomy (LAD) as part of hepatic resection for malignancies of the liver remains unclear. In this study, we aimed to report on the use cases and postoperative outcomes of liver resection and simultaneous LAD for hepatic malignancies (HM). MATERIALS AND METHODS: Clinicopathological data from patients who underwent surgery at 13 German centers from 2017 to 2022 (n = 3456) was extracted from the StuDoQ|Liver registry of the German Society of General and Visceral Surgery. Propensity-score matching (PSM) was performed to account for the extent of liver resection and patient demographics. RESULTS: LAD was performed in 545 (16%) cases. The most common indication for LAD was cholangiocarcinoma (CCA), followed by colorectal liver metastases (CRLM) and hepatocellular carcinoma (HCC). N+ status was found in 7 (8%), 59 (35%), and 56 cases (35%) for HCC, CCA, and CRLM, respectively (p < 0.001). The LAD rate was highest for robotic-assisted resections (28%) followed by open (26%) and laparoscopic resections (13%), whereas the number of resected lymph nodes was equivalent between the techniques (p = 0.303). LAD was associated with an increased risk of liver-specific postoperative complications, especially for patients with HCC. CONCLUSION: In this multicenter registry study, LAD was found to be associated with an increased risk of liver-specific complications. The highest rate of LAD was observed among robotic liver resections.

The Interplay of TGF-ß1 and Cholesterol Orchestrating Hepatocyte Cell Fate, EMT, and Signals for HSC Activation.

BACKGROUND & AIMS: Transforming growth factor-ß1 (TGF-ß1) plays important roles in chronic liver diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD involves various biological processes including dysfunctional cholesterol metabolism and contributes to progression to metabolic dysfunction-associated steatohepatitis and hepatocellular carcinoma. However, the reciprocal regulation of TGF-ß1 signaling and cholesterol metabolism in MASLD is yet unknown. METHODS: Changes in transcription of genes associated with cholesterol metabolism were assessed by RNA sequencing of murine hepatocyte cell line (alpha mouse liver 12/AML12) and mouse primary hepatocytes treated with TGF-ß1. Functional assays were performed on AML12 cells (untreated, TGF-ß1 treated, or subjected to cholesterol enrichment [CE] or cholesterol depletion [CD]), and on mice injected with adenovirus-associated virus 8-control/TGF-ß1. RESULTS: TGF-ß1 inhibited messenger RNA expression of several cholesterol metabolism regulatory genes, including rate-limiting enzymes of cholesterol biosynthesis in AML12 cells, mouse primary hepatocytes, and adenovirus-associated virus-TGF-ß1-treated mice. Total cholesterol levels and lipid droplet accumulation in AML12 cells and liver tissue also were reduced upon TGF-ß1 treatment. Smad2/3 phosphorylation after 2 hours of TGF-ß1 treatment persisted after CE or CD and was mildly increased after CD, whereas TGF-ß1-mediated AKT phosphorylation (30 min) was inhibited by CE. Furthermore, CE protected AML12 cells from several effects mediated by 72 hours of incubation with TGF-ß1, including epithelial-mesenchymal transition, actin polymerization, and apoptosis. CD mimicked the outcome of long-term TGF-ß1 administration, an effect that was blocked by an inhibitor of the type I TGF-ß receptor. In addition, the supernatant of CE- or CD-treated AML12 cells inhibited or promoted, respectively, the activation of LX-2 hepatic stellate cells. CONCLUSIONS: TGF-ß1 inhibits cholesterol metabolism whereas cholesterol attenuates TGF-ß1 downstream effects in hepatocytes.

Silver acetate coating promotes early vascularization of Dacron vascular grafts without inducing host tissue inflammation.

BACKGROUND: Silver acetate is frequently used as an antimicrobial coating of prosthetic vascular grafts. However, the effects of this coating on the early inflammatory and angiogenic host tissue response still remain elusive. Therefore, the aim of the present in vivo study was to analyze the biocompatibility and vascularization of silver acetate-coated and uncoated vascular grafts during the initial phase after implantation. METHODS: Two different prosthetic vascular grafts (ie, uncoated Dacron and silver acetate-coated Dacron Silver) were implanted into the dorsal skinfold chamber of C57BL/6 mice (n = 8 per group) to study angiogenesis and leukocytic inflammation at the implantation site by means of repetitive intravital fluorescence microscopy over a 14-day period. At the end of the in vivo experiments, collagen formation, apoptosis, and cell proliferation were analyzed in the newly developed granulation tissue surrounding the implants by histology and immunohistochemistry. RESULTS: During the initial 14 days after implantation, Dacron Silver exhibited an improved vascularization, as indicated by a significantly increased functional capillary density compared with Dacron. This was not associated with a stronger leukocytic inflammatory host tissue response to the implants. Moreover, silver acetate coating did not affect collagen formation, apoptosis, and cell proliferation at the implantation site. CONCLUSIONS: Silver acetate coating of prosthetic vascular grafts improves their early vascularization without inducing severe inflammatory side effects. Accordingly, this material modification crucially contributes to an improved incorporation of the implants into the host tissue, which may decrease the risk of vascular graft infection.

Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME.

This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4α, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4α), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell-derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.

Successful management of postoperative necrotizing pancreatitis after infrarenal abdominal aortic aneurysm repair.

We present a case of severe necrotizing pancreatitis that developed after elective repair of an abdominal aortic aneurysm. Surgeons are confronted in cases of postoperative acute pancreatitis with the dilemma of potential intraabdominal infection and the high risk of a subsequent infection of the retroperitoneal synthetic material. The therapeutic options range from a restrictive regime to radical necrosectomy and multivisceral resection.