Hepatocellular loss of mTOR aggravates tumor burden in nonalcoholic steatohepatitis-related HCC.

Obesity and associated nonalcoholic steatohepatitis (NASH) are on the rise globally. NASH became an important driver of hepatocellular carcinoma (HCC) in recent years. Activation of the central metabolic regulator mTOR (mechanistic target of rapamycin) is frequently observed in HCCs. However, mTOR inhibition failed to improve the outcome of HCC therapies, demonstrating the need for a better understanding of the molecular and functional consequences of mTOR blockade. We established a murine NASH-driven HCC model based on long-term western diet feeding combined with hepatocellular mTOR-inactivation. We evaluated tumor load and whole-body fat percentage via µCT-scans, analyzed metabolic blood parameters and tissue proteome profiles. Additionally, we used a bioinformatic model to access liver and HCC mitochondrial metabolic functions. The tumor burden was massively increased via mTOR-knockout. Several signs argue for extensive metabolic reprogramming of glucose, fatty acid, bile acid and cholesterol metabolism. Kinetic modeling revealed reduced oxygen consumption in KO-tumors. NASH-derived HCC pathogenesis is driven by metabolic disturbances and should be considered separately from those caused by other etiologies. We conclude that mTOR functions as tumor suppressor in hepatocytes especially under long-term western diet feeding. However, some of the detrimental consequences of this diet are attenuated by mTOR blockade.

Identifying radiomics signatures in body composition imaging for the prediction of outcome following pancreatic cancer resection.

Background: Computerized radiological image analysis (radiomics) enables the investigation of image-derived phenotypes by extracting large numbers of quantitative features. We hypothesized that radiomics features may contain prognostic information that enhances conventional body composition analysis. We aimed to investigate whether body composition-associated radiomics features hold additional value over conventional body composition analysis and clinical patient characteristics used to predict survival of pancreatic ductal adenocarcinoma (PDAC) patients. Methods: Computed tomography images of 304 patients undergoing elective pancreatic cancer resection were analysed. 2D radiomics features were extracted from skeletal muscle and subcutaneous and visceral adipose tissue (SAT and VAT) compartments from a single slice at the third lumbar vertebra. The study population was randomly split (80:20) into training and holdout subsets. Feature ranking with Least Absolute Shrinkage Selection Operator (LASSO) followed by multivariable stepwise Cox regression in 1000 bootstrapped re-samples of the training data was performed and tested on the holdout data. The fitted regression predictors were used as "scores" for a clinical (C-Score), body composition (B-Score), and radiomics (R-Score) model. To stratify patients into the highest 25% and lowest 25% risk of mortality compared to the middle 50%, the Harrell Concordance Index was used. Results: Based on LASSO and stepwise cox regression for overall survival, ASA ≥3 and age were the most important clinical variables and constituted the C-score, and VAT-index (VATI) was the most important body composition variable and constituted the B-score. Three radiomics features (SATI_original_shape2D_Perimeter, VATI_original_glszm_SmallAreaEmphasis, and VATI_original_firstorder_Maximum) emerged as the most frequent set of features and yielded an R-Score. Of the mean concordance indices of C-, B-, and R-scores, R-score performed best (0.61, 95% CI 0.56-0.65, p<0.001), followed by the C-score (0.59, 95% CI 0.55-0.63, p<0.001) and B-score (0.55, 95% CI 0.50-0.60, p=0.03). Kaplan-Meier projection revealed that C-, B, and R-scores showed a clear split in the survival curves in the training set, although none remained significant in the holdout set. Conclusion: It is feasible to implement a data-driven radiomics approach to body composition imaging. Radiomics features provided improved predictive performance compared to conventional body composition variables for the prediction of overall survival of PDAC patients undergoing primary resection.

Choice of Polymer, but Not Mesh Structure Variation, Reduces the Risk of Bacterial Infection with Staphylococcus aureus In Vivo.

BACKGROUND: Synthetic mesh material is of great importance for surgical incisional hernia repair. The physical and biochemical characteristics of the mesh influence mechanical stability and the foreign body tissue reaction. The influence on bacterial infections, however, remains ill-defined. The aim of the present study was to evaluate the influence of a modified mesh structure with variation in filament linking on the occurrence of bacterial infection that is indicated by the occurrence of CD68+, CD4+, and CD8+ cells in two different materials. METHODS: A total of 56 male Sprague Dawley rats received a surgical mesh implant in a subcutaneous abdominal position. The mesh of two different polymers (polypropylene (PP) and polyvinylidenfluoride (PVDF)) and two different structures (standard structure and bold structure with higher filament linking) were compared. During the implantation, the meshes were infected with Staphylococcus (S.) aureus. After 7 and 21 days, meshes were explanted, and the early and late tissue responses to infection were histologically evaluated. RESULTS: Overall, the inflammatory tissue response was higher at 7 days when compared to 21 days. At 7 days, PP meshes of the standard structure (PP-S) showed the strongest inflammatory tissue response in comparison to all the other groups. At 21 days, no statistically significant difference between different meshes was detected. CD8+ cytotoxic T cells showed a significant difference at 21 days but not at 7 days. PP meshes of both structures showed a higher infiltration of CD8+ T cells than PVDF meshes. CD4+ T helper cells differed at 7 days but not at 21 days, and PVDF meshes in a bold structure showed the highest CD4+ T cell count. The number of CD68+ macrophages was also significantly higher in PP meshes in a standard structure when compared to PVDF meshes at 21 days. CONCLUSION: The inflammatory tissue response to S. aureus infection appears to be highest during the early period after mesh implantation. PP meshes showed a higher inflammatory response than PVDF meshes. The mesh material appears to be more important for the risk of infection than the variation in filament linking.

No difference in outcomes between large- and small-pore meshes in a prospective, randomized, multicenter trial investigating open retromuscular meshplasty for incisional hernia repair.

STUDY DESIGN: A randomized, controlled, prospective multicenter clinical trial with a parallel group design was initiated in eight surgical centers to compare a large-pore polypropylene mesh (Ultrapro®) to a small-pore polypropylene mesh (Premilene®) within a standardized retromuscular meshplasty for incisional hernia repair. METHODS: Between 2004 and 2006, patients with a fascial defect with a minimum diameter of 4 cm after vertical midline laparotomy were recruited for the trial. Patients underwent retromuscular meshplasty with either a large-pore or a small-pore mesh to identify the superiority of the large-pore mesh. Follow-up visits were scheduled at 5 and 21 days and 4, 12, and 24 months after surgery. A clinical examination, a modified short form 36 (SF-36®), a daily activity questionnaire, and an ultrasound investigation of the abdominal wall were completed at every follow-up visit. The primary outcome criterion was foreign body sensation at the 12-month visit, and the secondary endpoint criteria were the occurrence of hematoma, seroma, and chronic pain within 24 months postoperatively. RESULTS: In 8 centers, 181 patients were included in the study. Neither foreign body sensation within the first year after surgery (27.5% Ultrapro®, 32.2% Premilene®) nor the time until the first occurrence of foreign body sensation within the first year was significantly different between the groups. Regarding the secondary endpoints, no significant differences could be observed. At the 2-year follow-up, recurrences occurred in 5 Ultrapro® patients (5.5%) and 4 Premilene® patients (4.4%). CONCLUSION: Despite considerable differences in theoretical and experimental works, we have not been able to identify differences in surgical or patient-reported outcomes between the use of large- and small-pore meshes for retromuscular incisional hernia repair. TRIAL REGISTRATION: Clinical Trials NCT04961346 (16.06.2021) retrospectively registered.

The impact of the COVID-19 outbreak on emergency general surgery in the first German "hotspot region" Aachen-Heinsberg-A multicentre retrospective cohort study.

This study aimed to observe the impact of the COVID-19 outbreak on acute general surgery in the first German "hotspot" regions of Heinsberg and Aachen, during the first months of the pandemic. The incidence and severity of acute appendicitis, acute cholecystitis and mechanical bowel obstruction, were compared between March and May 2020 and a control period (same months of the previous three years). Pre-, intra- and postoperative data was compared between three regional hospitals of Heinsberg and the closest maximum care, university hospital. A total of 592 operated patients were included, 141 belonging to the pandemic cohort and 451 to the historic cohort. The pandemic group showed higher rates of clinical peritonitis (38% vs. 27%, p = 0.015), higher rates of mean white blood cell count (13.2±4.4 /nl vs. 12.3±4.7 /nl, p = 0.044) and mean C-reactive protein (60.3±81.1 mg/l vs. 44.4±72.6 mg/l, p = 0.015) preoperatively. Specifically in patients with acute appendicitis, there were less patients with catarrhal appendicitis (23% vs. 35%, p = 0.021) and a tendency towards more advanced histological findings in the pandemic cohort. In the university hospital, a 42% reduction in acute operated cases was observed at the onset of the pandemic (n = 30 in 2020 vs. n = 52 in 2019), whereas in the peripheral hospitals of Heinsberg there was only a 10% reduction (n = 111 in 2020 vs. n = 123 in 2019). The onset of the COVID-19 pandemic in our region was accompanied by advanced preoperative and intraoperative findings in patients undergoing emergency general surgery. A greater reduction in acute operated surgical cases was observed at the university hospital, in contrast to the smaller hospitals of Heinsberg, suggesting a possible shift of emergency patients, requiring immediate operation, from maximum care hospital to the periphery.

Ultra-Fine Polyethylene Hernia Meshes Improve Biocompatibility and Reduce Intraperitoneal Adhesions in IPOM Position in Animal Models.

(1) Introduction: The intraperitoneal onlay mesh technique (IPOM) is widely used to repair incisional hernias. This method has advantages but suffers from complications due to intraperitoneal adhesion formation between the mesh and intestine. An ideal mesh minimizes adhesions and shows good biocompatibility. To address this, newly developed multifilamentous polyethylene (PET) meshes were constructed from sub-macrophage-sized monofilaments and studied regarding biocompatibility and adhesion formation. (2) Methods: We investigated fine (FPET, 72 filaments, 11 µm diameter each) and ultra-fine multifilament (UFPET, 700 filaments, 3 µm diameter each) polyethylene meshes for biocompatibility in subcutaneous implantation in rats. Adhesion formation was analyzed in the IPOM position in rabbits. Geometrically identical mono-filamentous polypropylene (PP) Bard Soft® PP meshes were used for comparison. Histologic and immune-histologic foreign body reactions were assessed in 48 rats after 7 or 21 days (four mesh types, with two different mesh types per rat; n = 6 per mesh type). Additionally, two different mesh types each were placed in the IPOM position in 24 rabbits to compile the Diamond peritoneal adhesion score after the same timeframes. The biocompatibility and adhesion score differences were analyzed with the Kruskal-Wallis nonparametric statistical test. (3) Results: Overall, FPET and, especially, UFPET showed significantly smaller foreign body granulomas compared to PP meshes. Longer observation periods enhanced the differences. Immunohistology showed no significant differences in the cellular immune response and proliferation. UFPET demonstrated significantly reduced peritoneal adhesion formation compared to all other tested meshes after 21 days. (4) Conclusions: Overall, FPET and, especially, UFPET demonstrated their suitability for IPOM hernia meshes in animal models by improving major aspects of the foreign body reaction and reducing adhesion formation.

Novel Elastic Threads for Intestinal Anastomoses: Feasibility and Mechanical Evaluation in a Porcine and Rabbit Model.

Gastrointestinal anastomoses are an important source of postoperative complications. In particular, the ideal suturing material is still the subject of investigation. Therefore, this study aimed to evaluate a newly developed suturing material with elastic properties made from thermoplastic polyurethane (TPU); Polyvinylidene fluoride (PVDF) and TPU were tested in two different textures (round and a modified, "snowflake" structure) in 32 minipigs, with two anastomoses of the small intestine sutured 2 m apart. After 90 days, the anastomoses were evaluated for inflammation, the healing process, and foreign body reactions. A computer-assisted immunohistological analysis of staining for Ki67, CD68, smooth muscle actin (SMA), and Sirius red was performed using TissueFAXS. Additionally, the in vivo elastic properties of the material were assessed by measuring the suture tension in a rabbit model. Each suture was tested twice in three rabbits; No major surgical complications were observed and all anastomoses showed adequate wound healing. The Ki67+ count and SMA area differed between the groups (F (3, 66) = 5.884, p = 0.0013 and F (3, 56) = 6.880, p = 0.0005, respectively). In the TPU-snowflake material, the Ki67+ count was the lowest, while the SMA area provided the highest values. The CD68+ count and collagen I/III ratio did not differ between the groups (F (3, 69) = 2.646, p = 0.0558 and F (3, 54) = 0.496, p = 0.686, respectively). The suture tension measurements showed a significant reduction in suture tension loss for both the TPU threads; Suturing material made from TPU with elastic properties proved applicable for intestinal anastomoses in a porcine model. In addition, our results suggest a successful reduction in tissue incision and an overall suture tension homogenization.

Machine learning prediction model for postoperative outcome after perforated appendicitis.

PURPOSE: Appendectomy for acute appendicitis is one of the most common operative procedures worldwide in both children and adults. In particular, complicated (perforated) cases show high variability in individual outcomes. Here, we developed and validated a machine learning prediction model for postoperative outcome of perforated appendicitis. METHODS: Retrospective analyses of patients with clinically and histologically verified perforated appendicitis over 10 years were performed. Demographic and surgical baseline characteristics were used as competing predictors of single-patient outcomes along multiple dimensions via a random forest classifier with stratified subsampling. To assess whether complications could be predicted in new, individual cases, the ensuing models were evaluated using a replicated 10-fold cross-validation. RESULTS: A total of 163 patients were included in the study. Sixty-four patients underwent laparoscopic surgery, whereas ninety-nine patients got a primary open procedure. Interval from admission to appendectomy was 9 ± 12 h and duration of the surgery was 74 ± 38 min. Forty-three patients needed intensive care treatment. Overall mortality was 0.6 % and morbidity rate was 15%. Severe complications as assessed by Clavien-Dindo > 3 were predictable in new cases with an accuracy of 68%. Need for ICU stay (> 24 h) could be predicted with an accuracy of 88%, whereas prolonged hospitalization (greater than 7-15 days) was predicted by the model with an accuracy of 76%. CONCLUSION: We demonstrate that complications following surgery, and in particular, health care system-related outcomes like intensive care treatment and extended hospitalization, may be well predicted at the individual level from demographic and surgical baseline characteristics through machine learning approaches.

Two Polyurethane Adhesives for PVDF Fixation Show Superior Biocompatibility in a Rat Model.

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

Safety of laparoscopic hepatectomy in patients with severe comorbidities - A propensity score matched analysis.

BACKGROUND: Laparoscopic hepatectomy (LH) is nowadays considered as the standard of care for various liver malignancies. However, studies focusing on perioperative outcome after LH in patients with severe comorbidities are still sparse. METHODS: 247 patients, who underwent LH between January 2016 and March 2020 at European surgical center Aachen Maastricht (ESCAM) were retrospectively analyzed regarding surgical outcome. All patients were categorized according to the ASA guidelines and a propensity score matched (PSM) analysis was performed to compare patients with severe comorbidities with patients with minor or no comorbidities. RESULTS: After PSM, no statistically significant differences regarding clinical characteristics were observed. We performed major resections in 26.4% of h-ASA (ASA > 2) patients and 19.4% of l-ASA (ASA≤2) patients, respectively (P = .322). Overall morbidity (Clavien-Dindo≥1) was observed more frequently in the h-ASA group (h-ASA: 25.0% vs. l-ASA: 8.3%; P = .007) while analysis of major morbidity (Clavien-Dindo≥3b) showed a non-significant tendency for more complications in h-ASA patients (h-ASA: 8.3% vs. l-ASA: 1.4%; P = .053). A subgroup analysis identified major resection (HR = 5.05; P = .006) as an independent risk factor for the occurrence of any postoperative complication and chronic kidney disease (HR = 22.59; P = .030) and liver fibrosis (HR = 30.16; P = .031) as risk factors for the occurrence of major complications in h-ASA patients. CONCLUSION: LH in patients with severe systemic comorbidities shows a strong tendency towards an increased rate of major complications. Careful patient selection with respect to the planned extent of resection and the presence of chronic kidney disease and liver fibrosis should be performed to improve perioperative results.

Incisional hernia repair by synthetic mesh prosthesis in patients with inflammatory bowel disease: a comparative analysis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have a high-life time risk undergoing abdominal surgery and are prone to develop incisional hernias (IH) in the postoperative course. Therefore, we investigated the role of IBD as perioperative risk factor in open ventral hernia repair (OVHR) as well as the impact of IBD on hernia recurrence during postoperative follow-up. METHODS: The postoperative course of 223 patients (Non-IBD (n = 199) and IBD (n = 34)) who underwent OVHR were compared by means of extensive group comparisons and binary logistic regressions. Hernia recurrence was investigated in the IBD group according to the Kaplan-Meier method and risk factors for recurrence determined by Cox regressions. RESULTS: General complications (≥ Clavien-Dindo I) occurred in 30.9% (72/233) and major complications (≥ Clavien-Dindo IIIb) in 7.7% (18/233) of the overall cohort with IBD being the single independent risk-factor for major complications (OR = 4.2, p = 0.007). Further, IBD patients displayed a recurrence rate of 26.5% (9/34) after a median follow-up of 36 months. Multivariable analysis revealed higher rates of recurrence in patients with ulcerative colitis (UC, 8/15, HR = 11.7) compared to patients with Crohn's disease (CD, 1/19, HR = 1.0, p = 0.021). CONCLUSION: IBD is a significant risk factor for major postoperative morbidity after OVHR. In addition, individuals with IBD show high rates of hernia recurrence over time with UC patients being more prone to recurrence than patients with CD.

Deletion of mTOR in liver epithelial cells enhances hepatic metastasis of colon cancer.

Activation of the mechanistic target of rapamycin (mTOR) pathway is frequently found in cancer, but mTOR inhibitors have thus far failed to demonstrate significant antiproliferative efficacy in the majority of cancer types. Besides cancer cell-intrinsic resistance mechanisms, it is conceivable that mTOR inhibitors impact on non-malignant host cells in a manner that ultimately supports resistance of cancer cells. Against this background, we sought to analyze the functional consequences of mTOR inhibition in hepatocytes for the growth of metastatic colon cancer. To this end, we established liver epithelial cell (LEC)-specific knockout (KO) of mTOR (mTORLEC ) mice. We used these mice to characterize the growth of colorectal liver metastases with or without partial hepatectomy to model different clinical settings. Although the LEC-specific loss of mTOR remained without effect on metastasis growth in intact liver, partial liver resection resulted in the formation of larger metastases in mTORLEC mice compared with wildtype controls. This was accompanied by significantly enhanced inflammatory activity in LEC-specific mTOR KO livers after partial liver resection. Analysis of NF-ĸB target gene expression and immunohistochemistry of p65 displayed a significant activation of NF-ĸB in mTORLEC mice, suggesting a functional importance of this pathway for the observed inflammatory phenotype. Taken together, we show an unexpected acceleration of liver metastases upon deletion of mTOR in LECs. Our results support the notion that non-malignant host cells can contribute to resistance against mTOR inhibitors and encourage testing whether anti-inflammatory drugs are able to improve the efficacy of mTOR inhibitors for cancer therapy. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

CT-Based Prediction of Liver Function and Post-PVE Hypertrophy Using an Artificial Neural Network.

BACKGROUND: This study aimed to evaluate whether hypertrophy after portal vein embolization (PVE) and maximum liver function capacity (LiMAx) are predictable by an artificial neural network (ANN) model based on computed tomography (CT) texture features. METHODS: We report a retrospective analysis on 118 patients undergoing preoperative assessment by CT before and after PVE for subsequent extended liver resection due to a malignant tumor at RWTH Aachen University Hospital. The LiMAx test was carried out in a subgroup of 55 patients prior to PVE. Associations between CT texture features and hypertrophy as well as liver function were assessed by a multilayer perceptron ANN model. RESULTS: Liver volumetry showed a median hypertrophy degree of 33.9% (16.5-60.4%) after PVE. Non-response, defined as a hypertrophy grade lower than 25%, was found in 36.5% (43/118) of the cases. The ANN prediction of the hypertrophy response showed a sensitivity of 95.8%, specificity of 44.4% and overall prediction accuracy of 74.6% (p < 0.001). The observed median LiMAx was 327 (248-433) µg/kg/h and was strongly correlated with the predicted LiMAx (R2 = 0.89). CONCLUSION: Our study shows that an ANN model based on CT texture features is able to predict the maximum liver function capacity and may be useful to assess potential hypertrophy after performing PVE.

Laparoscopic hepatectomy reduces postoperative complications and hospital stay in overweight and obese patients.

BACKGROUND: Laparoscopic liver surgery is currently considered the standard of care for various liver malignancies. However, studies focusing on perioperative outcome after laparoscopic hepatectomy (LH) in overweight patients are still sparse and its benefit compared to open hepatectomy (OH) is a matter of debate. AIM: To analyze postoperative outcomes in overweight [body mass index (BMI) over 25 kg/m²] and obese (BMI over 30 kg/m²) patients undergoing LH and compare postoperative outcome with patients undergoing OH. METHODS: Perioperative data of 68 overweight (BMI over 25 kg/m²) including a subcohort of obese (BMI over 30 kg/m²) patients (n = 27) who underwent LH at our institution between 2015 and 2019 were retrospectively analyzed regarding surgical outcome and compared to an equal number of patients undergoing OH. RESULTS: The mean BMI was 29.8 ± 4.9 kg/m2 in the LH group and 29.7 ± 3.6 kg/m2 in the OH group with major resections performed in 20.6% (LH) and 26.5% (OH) of cases, respectively. Operative time (194 ± 88 min vs 275 ± 131 min; P < 0.001) as well as intensive care (0.8 ± 0.7 d vs 1.1 ± 0.8 d; P = 0.031) and hospital stay (7.3 ± 3.6 d vs 15.7 ± 13.5 d; P < 0.001) were significant shorter in the LH group. Also, overall complications (20.6% vs 45.6%; P = 0.005) and major complications (1.5% vs 14.7%, P = 0.002) were observed less frequently after LH. An additional investigation analyzing the subgroup of obese patients who underwent LH (n = 27) and OH (n = 29) showed a shorter operative time (194 ± 81 min vs 260 ± 137 min; P = 0.009) and a reduced length of hospitalization (7.7 ± 4.3 d vs 17.2 ± 17 d; P < 0.001) but no difference in postoperative complications or overall cost. CONCLUSION: LH is safe and cost-effective in overweight and obese patients. Furthermore, LH is significantly associated with fewer postoperative complications and reduced hospital stay compared to OH in these patients.

Operative Time, Age, and Serum Albumin Predict Surgical Morbidity After Laparoscopic Liver Surgery.

Background. Laparoscopic liver resection (LLR) has emerged as a considerable alternative to conventional liver surgery. However, the increasing complexity of liver resection raises the incidence of postoperative complications. The aim of this study was to identify risk factors for postoperative morbidity in a monocentric cohort of patients undergoing LLR. Methods. All consecutive patients who underwent LLR between 2015 and 2019 at our institution were analyzed for associations between complications with demographics and clinical and operative characteristics by multivariable logistic regression analyses. Results. Our cohort comprised 156 patients who underwent LLR with a mean age of 60.0 ± 14.4 years. General complications and major perioperative morbidity were observed in 19.9% and 9.6% of the patients, respectively. Multivariable analysis identified age>65 years (HR = 2.56; P = .028) and operation time>180 minutes (HR = 4.44; P = .001) as significant predictors of general complications (Clavien ≥1), while albumin<4.3 g/dl (HR = 3.66; P = .033) and also operative time (HR = 23.72; P = .003) were identified as predictors of major postoperative morbidity (Clavien ≥3). Conclusion. Surgical morbidity is based on patient- (age and preoperative albumin) and procedure-related (operative time) characteristics. Careful patient selection is key to improve postoperative outcomes after LLR.

A peritoneal defect covered by intraperitoneal mesh prosthesis effects an increased and distinctive foreign body reaction in a minipig model.

BACKGROUND: The incidence of incisional hernia is with up to 30% one of the frequent long-term complication after laparotomy. After establishing minimal invasive operations, the laparoscopic intraperitoneal onlay mesh technique (lap. IPOM) was first described in 1993. Little is known about the foreign body reaction of IPOM-meshes, which covered a defect of the parietal peritoneum. This is becoming more important, since IPOM procedure with peritoneal-sac resection and hernia port closing (IPOM plus) is more frequently used. METHODS: In 18 female minipigs, two out of three Polyvinylidene-fluoride (PVDF) -meshes (I: standard IPOM; II: IPOM with modified structure [bigger pores]; III: IPOM with the same structure as IPOM II + degradable hydrogel-coating) were placed in a laparoscopic IPOM procedure. Before mesh placement, a 2x2cm peritoneal defect was created. After 30 days, animals were euthanized, adhesions were evaluated by re-laparoscopy and mesh samples were explanted for histological and immunohistochemichal investigations. RESULTS: All animals recovered after implantation and had no complications during the follow-up period. Analysing foreign body reaction, the IPOM II mesh had a significant smaller inner granuloma, compared to the other meshes (IPOM II: 8.4 µm ± 1.3 vs. IPOM I 9.1 µm ± 1.3, p < 0.001). The degradable hydrogel coating does not prevent adhesions measured by Diamond score (p = 0.46). A peritoneal defect covered by a standard or modified IPOM mesh was a significant factor for increasing foreign body granuloma, the amount of CD3+ lymphocytes, CD68+ macrophages and decrease of pore size. CONCLUSION: A peritoneal defect covered by IPOM prostheses leads to an increased foreign body reaction compared to intact peritoneum. Whenever feasible, a peritoneal defect should be closed accurately before placing an IPOM-mesh to avoid an excessive foreign body reaction and therefore inferior biomaterial properties of the prosthesis.

First Result of a Tailored Progressive Multistep Approach for the Treatment of Aorto-esophageal Fistulae.

BACKGROUND: Aorto-esophageal fistulae (AEFs) are a rare but serious and life-threatening disease of the mediastinum. Especially, AEF in the presence of infected stent grafts, for example, after thoracic endovascular aortic repair (TEVAR) is only curable by a multistage interdisciplinary surgical approach. This study presents the results of our four-stage approach consisting of bridging TEVAR, esophagectomy, complete stent removal followed by total bovine tube aortic replacement (TBTAR), and finally esophageal reconstruction. METHODS: A case series of four patients from our department receiving a four-stage treatment of AEF is presented in this study. Retrospective database analysis focusing on overall survival, duration of intensive care unit and total hospital stay until discharge, complications, surgical time frame, and completion of chosen surgical treatment course was performed. RESULTS: Overall, four patients surgically treated for AEF since May 2015 were included. A 30-day mortality was 0%, and overall survival at 1 year was 75%. All patients survived more than 5 months and could be discharged after TEVAR and esophagectomy. TBTAR could be performed in two of four patients (50%). Esophageal reconstruction was completed in all patients. Average follow-up was 20.3 ± 1.7 months or until death. CONCLUSION: The acute management of AEF using this approach seems satisfactory, especially for reducing acute short-term mortality. Complete restoration of the circulatory system and digestive tract remains challenging and is associated with high morbidity. We support the application of bridging TEVAR with a staggered approach to further surgical treatment individually tailored to the patient.

Minimally Invasive Thoracoabdominal Esophagectomy Is Superior to Minimally Invasive Gastrectomy in Terms of Health-Related Quality of Life.

Background and Objectives: There are two operative approaches for adenocarcinomas of the esophagogastric junction: thoracoabdominal esophagectomy or transhiatal extended gastrectomy. Both procedures can be performed minimally invasively. Dependent on the exact localization of the tumor, both approaches are feasible. Aim of this study was to compare the health-related quality of life (HRQOL) of patients after minimally invasive esophagectomy (MIE) with patients who underwent minimally invasive gastrectomy (MIG). Methods: All patients who underwent MIE or gastrectomy for malignoma since 2014 were identified from our clinical database. The identified patients were contacted and asked to fill out a quality of life questionnaire (QLQ) for general and gastrointestinal QOL (European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-OG25). Results: Global HRQOL scores were higher in patients after MIE than after MIG. After MIE, global HRQOL scores were close to the control population. In cancer-specific syndromes, patients after MIE reported lower symptom scores for financial problems, eating, reflux, and eating with others than patients after MIG. Conclusion: In terms of HRQOL, MIE proved superior to MIG in long-term follow-up in this study. Patients after MIE reported a HRQOL close to that of a healthy reference population.

Cross-section modified and highly elastic sutures reduce tissue incision and show comparable biocompatibility: in-vitro and in-vivo evaluation of novel thermoplastic urethane surgical threads.

Surgical sutures are indispensable for a vast majority of operative procedures. An ideal suture is characterized by high tissue compliance without cutting into the mended tissue and optimal biocompatibility. Therefore, we assessed these mechanical and biological properties for novel elastic thermoplastic polyurethane (TPU) and cross-sectional modified "snowflake" sutures. Circular and "snowflake"-shaped TPU threads were manufactured and compared to similar surface modified polyvinylidene fluoride (PVDF) sutures. Regular PVDF sutures were used as the control group. Single-axis tensile test with and without gelatinous tissue surrogates were performed to evaluate the suture incision into the specimens. Biocompatibility was evaluated by subcutaneous implantation (n = 18) in rats for 7 and 21 days. Histology and immunohistology was conducted for assessment of the foreign body reaction. Regular and modified TPU threads showed a significant reduction of incision into the tissue surrogates compared to the control. Both TPU sutures and the modified PVDF sutures achieved comparable biocompatibility versus regular PVDF threads. Detailed histology revealed novel tissue integration into the notches of the surface modified sutures, we termed this newly shaped granuloma "intrafilamentous" granuloma. Elastic TPU threads showed a significant reduction of tissue surrogate incision and suture tension loss. Biocompatibility did not significantly differ from standard PVDF. Histology demonstrated tissue ingrowth following the surface modification of the suture referred to as "intrafilamentous" granuloma. Further in vivo studies are required to illuminate the exact potential of the new sutures to optimize intestinal anastomosis.

Mouse Models of Nonalcoholic Steatohepatitis: Head-to-Head Comparison of Dietary Models and Impact on Inflammation and Animal Welfare.

A variety of dietary nonalcoholic steatohepatitis (NASH) mouse models are available, and choosing the appropriate mouse model is one of the most important steps in the design of NASH studies. In addition to the histopathological and metabolic findings of NASH, a sufficient mouse model should guarantee a robust clinical status and good animal welfare. Three different NASH diets, a high-fat diet (HFD60), a western diet (WD), and a cafeteria diet (CAFD), were fed for 12 or 16 weeks. Metabolic assessment was conducted at baseline and before scheduled sacrifice, and liver inflammation was analyzed via fluorescence-associated cell sorting and histopathological examination. Clinical health conditions were scored weekly to assess the impact on animal welfare. The HFD60 and WD were identified as suitable NASH mouse models without a significant strain on animal welfare. Furthermore, the progression of inflammation and liver fibrosis was associated with a decreased proportion of CD3+ NK1.1+ cells. The WD represents a model of advanced-stage NASH, and the HFD60 is a strong model of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. However, the CAFD should not be considered a NASH model.