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.

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.

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.

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.

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.

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.

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.

Influence of suture technique on anastomotic leakage rate-a retrospective analyses comparing interrupted-versus continuous-sutures.

PURPOSE: While many hospitals consider a continuous sutured colonic anastomosis with monofilamental fiber the current state of the art, others have advocated for interrupted sutures as the gold standard. The aim of the study was to evaluate the influence of suture technique on leakage rate (primary endpoint), wound infections, postoperative stay, and mortality. METHODS: Retrospective analyses of 347 patients (273 elective, 74 urgent) over 6 years with a handsewn colonic anastomosis (190 interrupted, 157 continuous), excluding sigma and rectum anastomosis. Demographic and surgical baseline characteristics were used as competing predictors. RESULTS: Overall leakage rate was 9% but strongly dependent on suture technique (interrupted: 16%; continuous: 2.5%; p = 0.001) yielding an odds ratio of 5.10 [95% CI: 2.55, 6.71] (relative risk of leakage). No other variable showed a significant influence on leakage rate. Postoperative stay was prolonged in the interrupted suture group (23 ± 15 vs. 16 ± 11 days; p = 0.000, attributable effect 7.5 days [4.7, 10.3]). CONCLUSIONS: Our results indicate a highly significant reduction of anastomotic leakage rate and postoperative stay that generalize to the underlying population by continuous sutures in handsewn colonic anastomosis. In the absence of randomized prospective studies, the current results provide the yet strongest evidence for the superiority of continuous sutures.

Impact of body composition on survival and morbidity after liver resection in hepatocellular carcinoma patients.

BACKGROUND: Hepatocellular carcinoma is the most common innate liver tumor. Due to improved surgical techniques, even extended resections are feasible, and more patients can be treated with curative intent. As the liver is the central metabolic organ, preoperative metabolic assessment is crucial for risk stratification. Sarcopenia, obesity and sarcopenic obesity characterize body composition and metabolic status. Here we present the impact of body composition on survival after liver resection in patients with hepatocellular carcinoma. METHODS: A retrospective database analysis of 70 patients who were assigned for liver resection due to hepatocellular carcinoma was conducted. For assessment of sarcopenia and obesity, skeletal muscle surface area was measured at lumbar vertebra 3 level (L3) in preoperative four-phase contrast enhanced abdominal CT scans, and L3 muscle index and body fat percentage were calculated. RESULTS: Univariate analysis comparing the survival curves using the score test demonstrated superior postoperative overall survival for sarcopenic (P = 0.035) and sarcopenic obese (P = 0.048) patients as well as a trend favoring obese (P = 0.130) subjects. Whereas multivariate analysis could not identify significant difference in postoperative survival regarding sarcopenia, obesity or sarcopenic obesity. Only large tumor size, multifocal disease and male gender were risk factors for long-term survival. CONCLUSIONS: Sarcopenia, obesity and sarcopenic obesity are indeed no risk factors for poor postoperative survival in this study. Our data do not support the evaluation of sarcopenia, obesity and sarcopenic obesity before liver resection in hepatocellular carcinoma patients.

A new device to prevent fascial retraction in the open abdomen - proof of concept in vivo.

BACKGROUND: An open abdomen is often necessary for survival of patients after peritonitis, compartment syndrome, or in damage control surgery. However, abdominal wall retraction relieves delays and complicates abdominal wall closure. The principle of the newly fascia preserving device (FPD) is the application of anteriorly directed traction on both fascial edges over an external support through a longitudinal beam to relieve increased abdominal pressure and prevent fascial retraction. METHODS: Twelve pigs were randomly divided into two groups. Both groups underwent midline laparotomy under general anesthesia. Group one was treated with the new device, group two served as controls. The tension for closing the abdominal fascia was measured immediately after laparotomy as well as at 24 and 48 h. Vital parameters and ventilation pressure were recorded. Post mortem, all fascial tissues were histologically examined. RESULTS: All pigs demonstrated increases in abdominal circumference. In both groups, forces for closing the abdomen increased over the observation period. Concerning the central closing force after 24 h we saw a significant lower force in the FPD group (14.4 ± 3 N) vs. control group (21.6 ± 5.7 N, p < 0.001). By testing the main effects using an ANOVA analysis we found a significant group related effect concerning closing force and abdominal circumference of the FDP-group vs. control group (p < 0.001; p < 0.001). The placement of the device on chest and pelvis did not influence vital parameters and ventilation pressure. Histologic exam detected no tissue damage. CONCLUSIONS: This trial shows the feasibility to prevent fascial retraction during the open abdomen by using the new device. Thus, it is expected that an earlier closure of the abdominal wall will be possible, and a higher rate of primary closure will be attained.

A Newly Established Murine Cell Line as a Model for Hepatocellular Cancer in Non-Alcoholic Steatohepatitis.

Non-alcoholic steatohepatitis (NASH) has become a major risk factor for hepatocellular cancer (HCC) due to the worldwide increasing prevalence of obesity. However, the pathophysiology of NASH and its progression to HCC is incompletely understood. Thus, the aim of this study was to generate a model specific NASH-derived HCC cell line. A murine NASH-HCC model was conducted and the obtained cancer cells (N-HCC25) were investigated towards chromosomal aberrations, the expression of cell type-specific markers, dependency on nutrients, and functional importance of mTOR. N-HCC25 exhibited several chromosomal aberrations as compared to healthy hepatocytes. Hepatocytic (HNF4), EMT (Twist, Snail), and cancer stem cell markers (CD44, EpCAM, CK19, Sox9) were simultaneously expressed in these cells. Proliferation highly depended on the supply of glucose and FBS, but not glutamine. Treatment with a second generation mTOR inhibitor (KU-0063794) resulted in a strong decrease of cell growth in a dose-dependent manner. In contrast, a first generation mTOR inhibitor (Everolimus) only slightly reduced cell proliferation. Cell cycle analyses revealed that the observed growth reduction was most likely due to G1/G0 cell cycle arrest. These results indicate that N-HCC25 is a highly proliferative HCC cell line from a NASH background, which might serve as a suitable in vitro model for future investigations of NASH-derived HCC.

AK03, a new recombinant fibrinogenase prevents abdominal adhesions in a rat model without systemic side effects.

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

A New Physiologic Mouse Model of One Anastomosis Gastric Bypass.

BACKGROUND: One anastomosis gastric bypass (OAGB) is a modern metabolic operation that has been demonstrated to be a rapid, safe, and effective procedure. As for other bariatric operations, the mechanisms and long-term effects of this procedure remain largely unknown and are difficult to address in human studies. Here, we present a new physiologic mouse model for mechanistic and long-term investigations. METHODS: Six-week-old C57Bl/6 mice were fed a high-fat diet for 12 weeks and scheduled for OAGB or sham operation. Mice were observed for 2 weeks after the operation, and weight and metabolic condition were monitored. RESULTS: Six mice were used to adapt the surgical technique. Afterwards, another 7 mice were scheduled for OAGB without further complications. The newly established OAGB procedure resulted in significant weight loss and improvement of glucose metabolism 2 weeks after the operation. CONCLUSIONS: The operation presented here is an easy-to-learn and physiologic mouse model of OAGB that can be used for further studies in mice.

Influence of gentamicin-coded PVDF suture material on the healing of intestinal anastomosis in a rat model.

PURPOSE: Intestinal anastomosis is a fundamental procedure in general surgery and required to restore intestinal continuity following resection. The aim of this study was to evaluate whether a gentamicin-coated polyvinylidene fluoride (PVDF) suture material has beneficial effect on anastomotic healing. METHODS: Ninety Sprague-Dawley rats were divided into three groups: a PVDF-suture group, a gentamicin-coated PVDF (GPVDF)-suture group and a control group using Maxon® (polyglycolid-co-trimethylene carbonate). For each animal, a colonic anastomosis was performed. Ten animals from each group were sacrificed on postoperative days 3, 5, and 14. Measurements of anastomotic bursting pressure were performed on days 3 and 5. At each time, collagen type I/III ratio, MMP 2 and MMP-9 expression and the proliferation index (Ki67) were analyzed. RESULTS: In total, 90 animals underwent surgery without postoperative complications. Bursting strength in the GPVDF group was significantly elevated on day 5. Immunohistochemistry showed significant increase of the collagen type I/III ratio for PVDF and GPVDF on days 3 and 5. MMP2 was significantly increased for PVDF on days 3 and 5 and for GPVDF on day 5. The analysis of MMP9 revealed significant increase compared to control on day 3 and 5 (GPVDF) as well as on day 5 (PVDF). Staining for Ki67 revealed a significant elevation on postoperative day 3 for the PVDF and the GPVDF group. CONCLUSIONS: The present data shows the feasibility of PVDF as suture material for colonic anastomosis and confirms the ability of gentamicin to increase the stability of colonic anastomosis when used as coating material.

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.

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.

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.

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.

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.