Metavert synergises with standard cytotoxics in human PDAC organoids and is associated with transcriptomic signatures of therapeutic response.

BACKGROUND: Despite some recent advances, pancreatic ductal adenocarcinoma (PDAC) remains a growing oncological challenge. New drugs capable of targeting more than one oncogenic pathway may be one way to improve patient outcomes. This study characterizes the effectiveness of Metavert a first-in-class dual inhibitor of GSK3-ß and histone deacetylase in treating PDAC as a single agent or in combination with standard cytotoxics. METHODS: Thirty-six Patient-Derived Organoids (hPDOs) characterised by RNASeq and whole exome sequencing were treated with Metavert alone or in combination with standard cytotoxics. Transcriptomic signatures (TS) representing sensitivity to Metavert alone or sensitivity to Metavert + irinotecan (IR) were evaluated in 47 patient samples, chemo-naïve in 26 and post-chemotherapy in 21 (gemcitabine=5; FOLFIRINOX=14, both=2) with companion multiplexed immunofluorescence and RNASeq data. RESULTS: Metavert combined with gemcitabine, irinotecan, 5FU, oxaliplatin, and paclitaxel was synergistic in the hPDOs. Basal-subtype hPDOs were more sensitive to Metavert alone whereas the Metavert+IR combination exhibited synergy in Classical-subtype hPDOs with increased apoptosis and autophagy. hPDO-derived TS evaluated in PDAC tissues demonstrated that Metavert-TSHi samples were enriched for mRNA splicing and DNA repair processes; they were associated with Basal-like tissues but also with GATA6+ve-chemo-naïve samples and were higher following gemcitabine but not FOLFIRINOX treatment. In contrast, Metavert+IR-TSHI samples were enriched for TP53 pathways; they were associated with Classical-like pretreatment samples and with GATA6+ve/KRT17+ve hybrid cell types following FOLFIRINOX, but not gemcitabine treatment, and were unrelated to transcriptional subtypes. CONCLUSIONS: Metavert as a single agent and in combination with irinotecan offers novel strategies for treating pancreatic cancer.

[Sex differences in pancreatic cancer]. / Geschlechtsunterschiede beim Pankreaskarzinom.

This review article discusses the currently available evidence on the importance of biological and social sex in pancreatic cancer in the context of the operative, perioperative and multimodal treatment. In pancreatic cancer there are gender differences with respect to the incidence, treatment response and prognosis. Sex significantly influences both innate and adaptive immune responses, thereby affecting treatment response and survival rates. Women are less likely to receive systemic treatment and tend to wait longer for surgery but have better perioperative outcomes after pancreatic resection. Overall, female pancreatic cancer patients seem to have longer survival under treatment; however, they report a subjectively lower quality of life and higher disease burden.

Preoperative Chemoradiotherapy vs Chemotherapy for Adenocarcinoma of the Esophagogastric Junction: A Network Meta-Analysis.

Importance: The prognosis of patients with adenocarcinoma of the esophagus and esophagogastric junction (AEG) is poor. From current evidence, it remains unclear to what extent preoperative chemoradiotherapy (CRT) or preoperative and/or perioperative chemotherapy achieve better outcomes than surgery alone. Objective: To assess the association of preoperative CRT and preoperative and/or perioperative chemotherapy in patients with AEG with overall survival and other outcomes. Data Sources: Literature search in PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and International Clinical Trials Registry Platform was performed from inception to April 21, 2023. Study Selection: Two blinded reviewers screened for randomized clinical trials comparing preoperative CRT plus surgery with preoperative and/or perioperative chemotherapy plus surgery, 1 intervention with surgery alone, or all 3 treatments. Only data from participants with AEG were included from trials that encompassed mixed histology or gastric cancer. Among 2768 initially identified studies, 17 (0.6%) met the selection criteria. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed for extracting data and assessing data quality by 2 independent extractors. A bayesian network meta-analysis was conducted using the 2-stage approach. Main Outcomes and Measures: Overall and disease-free survival, postoperative morbidity, and mortality. Results: The analyses included 2549 patients (2206 [86.5%] male; mean [SD] age, 61.0 [9.4] years) from 17 trials (conducted from 1989-2016). Both preoperative CRT plus surgery (hazard ratio [HR], 0.75 [95% credible interval (CrI), 0.62-0.90]; 3-year difference, 105 deaths per 1000 patients) and preoperative and/or perioperative chemotherapy plus surgery (HR, 0.78 [95% CrI, 0.64-0.91]; 3-year difference, 90 deaths per 1000 patients) showed longer overall survival than surgery alone. Comparing the 2 modalities yielded similar overall survival (HR, 1.04 [95% CrI], 0.83-1.28]; 3-year difference, 15 deaths per 1000 patients fewer for CRT). Similarly, disease-free survival was longer for both modalities compared with surgery alone. Postoperative morbidity was more frequent after CRT plus surgery (odds ratio [OR], 2.94 [95% CrI, 1.01-8.59]) than surgery alone. Postoperative mortality was not significantly more frequent after CRT plus surgery than surgery alone (OR, 2.50 [95% CrI, 0.66-10.56]) or after chemotherapy plus surgery than CRT plus surgery (OR, 0.44 [95% CrI, 0.08-2.00]). Conclusions and Relevance: In this meta-analysis of patients with AEG, both preoperative CRT and preoperative and/or perioperative chemotherapy were associated with longer survival without relevant differences between the 2 modalities. Thus, either of the 2 treatments may be recommended to patients.

Impact of Radiotherapy on Endotracheal Intubation Quality Metrics in Patients with Esophageal Cancer: A Challenge for Advanced Airway Management?

(1) Background: Currently, no data are available in the literature investigating the influence of radiotherapy (RT) on endotracheal intubation success in patients with esophageal cancer. This study aims to evaluate the impact of RT on endotracheal intubation quality metrics in patients with esophageal cancer. (2) Methods: Patients with esophageal cancer who underwent RT followed by surgery between 2012 and 2023 at the University Hospital Heidelberg, Germany, were retrospectively analyzed. (3) Results: Fifty-five patients, predominantly males 65.5% with a mean age of 64 years, were enrolled. Overall, 81.8% of the patients had an ASA class of III, followed by 27.2% ASA II. The mean prescribed cumulative total dose to the primary tumor and lymph node metastasis was 48.2 Gy with a mean single dose of 1.8 Gy. The mean laryngeal total dose was 40.0 Gy. Direct laryngoscopy was performed in 80.0% of cases, followed by 12.1% videolaryngoscopy, and 7.2% required fiberoptic intubation. Overall, 96.4% of patients were successfully intubated on the first attempt. (4) Conclusions: It has been demonstrated that post-RT effects can increase the risk of airway management difficulties and complications. The results of our study did not indicate any evidence of impaired advanced airway management in patients with esophageal cancer who had undergone RT.

Low intraoperative end-tidal carbon dioxide levels are associated with improved recurrence-free survival after elective colorectal cancer surgery.

STUDY OBJECTIVE: Higher levels of carbon dioxide (CO2) increase the invasive abilities of colon cancer cells in vitro. Studies assessing target values for end-tidal CO2 concentrations (EtCO2) to improve surgical outcome after colorectal cancer surgery are lacking. Therefore, we evaluated whether intraoperative EtCO2 was associated with differences in recurrence-free survival after elective colorectal cancer (CRC) surgery. DESIGN: Single center, retrospective analysis. SETTING: Anesthesia records, surgical databases and hospital information system of a tertiary university hospital. PATIENTS: We analyzed 528 patients undergoing elective resection of colorectal cancer at Heidelberg University Hospital between 2009 and 2018. INTERVENTIONS: None. MEASUREMENTS: Intraoperative mean EtCO2 values were calculated. The study cohort was equally stratified into low-and high-EtCO2 groups. The primary endpoint measure was recurrence-free survival until last known follow-up. Groups were compared using Kaplan-Meier analysis. Cox-regression analysis was used to control for covariates. Sepsis, reoperations, surgical site infections and cardiovascular events during hospital stay, and overall survival were secondary outcomes. MAIN RESULTS: Mean EtCO2 was 33.8 mmHg ±1.2 in the low- EtCO2 group vs. 37.3 mmHg ±1.6 in the high-EtCO2 group. Median follow-up was 3.8 (Q1-Q3, 2.5-5.1) years. Recurrence-free survival was higher in the low-EtCO2 group (log-rank-test: p = .024). After correction for confounding factors, lower EtCO2 was associated with increased recurrence-free survival (HR = 1.138, 95%-CI:1.015-1.276, p = .027); the hazard for the primary outcome decreased by 12.1% per 1 mmHg decrease in mean EtCO2. 1-year and 5-year survival was also higher in the low-EtCO2 group. We did not find differences in the other secondary endpoints. CONCLUSIONS: Lower intraoperative EtCO2 target values in CRC surgery might benefit oncological outcome and should be evaluated in confirmative studies.

Multiscale and multimodal imaging for three-dimensional vascular and histomorphological organ structure analysis of the pancreas.

Exocrine and endocrine pancreas are interconnected anatomically and functionally, with vasculature facilitating bidirectional communication. Our understanding of this network remains limited, largely due to two-dimensional histology and missing combination with three-dimensional imaging. In this study, a multiscale 3D-imaging process was used to analyze a porcine pancreas. Clinical computed tomography, digital volume tomography, micro-computed tomography and Synchrotron-based propagation-based imaging were applied consecutively. Fields of view correlated inversely with attainable resolution from a whole organism level down to capillary structures with a voxel edge length of 2.0 µm. Segmented vascular networks from 3D-imaging data were correlated with tissue sections stained by immunohistochemistry and revealed highly vascularized regions to be intra-islet capillaries of islets of Langerhans. Generated 3D-datasets allowed for three-dimensional qualitative and quantitative organ and vessel structure analysis. Beyond this study, the method shows potential for application across a wide range of patho-morphology analyses and might possibly provide microstructural blueprints for biotissue engineering.

Cavitron ultrasonic surgical aspirator (CUSA) compared with conventional pancreatic transection in distal pancreatectomy: study protocol for the randomised controlled CUSA-1 pilot trial.

BACKGROUND: Postoperative pancreatic fistula (POPF) remains the most common and serious complication after distal pancreatectomy. Many attempts at lowering fistula rates have led to unrewarding insignificant results as still up to 30% of the patients suffer from clinically relevant POPF. Therefore, the development of new innovative methods and procedures is still a cornerstone of current surgical research.The cavitron ultrasonic surgical aspirator (CUSA) device is a well-known ultrasound-based parenchyma transection method, often used in liver and neurosurgery which has not yet been thoroughly investigated in pancreatic surgery, but the first results seem very promising. METHODS: The CUSA-1 trial is a randomised controlled pilot trial with two parallel study groups. This single-centre trial is assessor and patient blinded. A total of 60 patients with an indication for open distal pancreatectomy will be intraoperatively randomised after informed consent. The patients will be randomly assigned to either the control group with conventional pancreas transection (scalpel or stapler) or the experimental group, with transection using the CUSA device. The primary safety endpoint of this trial will be postoperative complications ≥grade 3 according to the Clavien-Dindo classification. The primary endpoint to investigate the effect will be the rate of POPF within 30 days postoperatively according to the ISGPS definition. Further perioperative outcomes, including postpancreatectomy haemorrhage, length of hospital stay and mortality will be analysed as secondary endpoints. DISCUSSION: Based on the available literature, CUSA may have a beneficial effect on POPF occurrence after distal pancreatectomy. The rationale of the CUSA-1 pilot trial is to investigate the safety and feasibility of the CUSA device in elective open distal pancreatectomy compared with conventional dissection methods and gather the first data on the effect on POPF occurrence. This data will lay the groundwork for a future confirmatory multicentre randomised controlled trial. ETHICS AND DISSEMINATION: The CUSA-1 trial protocol was approved by the ethics committee of the University of Heidelberg (No. S-098/2022). Results will be published in an international peer-reviewed journal and summaries will be provided in lay language to study participants and their relatives. TRIAL REGISTRATION NUMBER: DRKS00027474.

Results of robotic liver surgery in association with IWATE criteria - the first 100 cases.

BACKGROUND: Aim of the current study was to present the results of the implementation phase of a robotic liver surgery program and to assess the validity of the IWATE difficulty score in predicting difficulty and postoperative complications in robotic liver surgery. METHODS: Based on the prospective database of the Interdisciplinary Robotic Center of Ulm University Hospital, the first 100 robotic liver surgeries were identified and analyzed. Perioperative parameters (duration of surgery and blood loss) and postoperative parameters including morbidity, mortality, and length of hospital stay were assessed and the results were compared between different IWATE difficulty categories. RESULTS: From November 2020 until January 2023, 100 robotic liver surgeries were performed (41 female, 59 male; median age 60.6 years, median BMI 25.9 kg/m2). Median duration of surgery was 180 min (IQR: 128.7), and median blood loss was 300 ml (IQR: 550). Ninety-day mortality was 2%, and overall morbidity was 21%, with major complications occurring in 13% of patients (≥ grade 3 according to Clavien/Dindo). A clinically relevant postoperative biliary leakage was observed in 3 patients. Posthepatectomy liver failure occurred in 7% (4 Grade A, 3 Grade B). Duration of surgery (p < 0.001), blood loss (p < 0.001), CCI (p = 0.004), overall morbidity (p = 0.004), and length of hospital stay (p < 0.001) were significantly increased in the IWATE 'expert' category compared to lower categories. DISCUSSION: Robotic surgery offers a minimally invasive approach for liver surgery with favorable clinical outcomes, even in the implementation phase. In the current study the IWATE difficulty score had the ability to predict both difficulty of surgery as well as postoperative outcomes when assessing the complexity of robotic liver surgery. Therefore, the role of the IWATE score in predicting these outcomes highlights its importance as a tool in surgical planning and decision-making.

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.

Tranexamic Acid Administration During Liver Transplantation Is Not Associated With Lower Blood Loss or With Reduced Utilization of Red Blood Cell Transfusion.

BACKGROUND: Current clinical guidelines recommend antifibrinolytic treatment for liver transplantation to reduce blood loss and transfusion utilization. However, the clinical relevance of fibrinolysis during liver transplantation is questionable, a benefit of tranexamic acid (TXA) in this context is not supported by sufficient evidence, and adverse effects are also conceivable. Therefore, we tested the hypothesis that use of TXA is associated with reduced blood loss. METHODS: We performed a retrospective cohort study on patients who underwent liver transplantation between 2004 and 2017 at Heidelberg University Hospital, Heidelberg, Germany. Univariable and multivariable linear regression analyses were used to determine the association between TXA administration and the primary end point intraoperative blood loss and the secondary end point intra- and postoperative red blood cell (RBC) transfusions. For further secondary outcome analyses, the time to the first occurrence of a composite end point of hepatic artery thrombosis, portal vein thrombosis, and thrombosis of the inferior vena cava were analyzed using a univariable and multivariable Cox proportional hazards model. RESULTS: Data from 779 transplantations were included in the final analysis. The median intraoperative blood loss was 3000 mL (1600-5500 mL). Intraoperative TXA administration occurred in 262 patients (33.6%) with an average dose of 1.4 ± 0.7 g and was not associated with intraoperative blood loss (regression coefficient B, -0.020 [-0.051 to 0.012], P = .226) or any of the secondary end points (intraoperative RBC transfusion; regression coefficient B, 0.023 [-0.006 to 0.053], P = .116), postoperative RBC transfusion (regression coefficient B, 0.007 [-0.032 to 0.046], P = .717), and occurrence of thrombosis (hazard ratio [HR], 1.110 [0.903-1.365], P = .321). CONCLUSIONS: Our data do not support the use of TXA during liver transplantation. Physicians should exercise caution and consider individual factors when deciding whether or not to administer TXA.

Clinical Research in Renal Transplantation: A Bibliometric Perspective on a Half-century of Innovation and Progress.

BACKGROUND: Groundbreaking biomedical research has transformed renal transplantation (RT) into a widespread clinical procedure that represents the mainstay of treatment for end-stage kidney failure today. Here, we aimed to provide a comprehensive bibliometric perspective on the last half-century of innovation in clinical RT. METHODS: The Web of Science Core Collection was used for a comprehensive screening yielding 123 303 research items during a 50-y period (January 1973-October 2022). The final data set of the 200 most-cited articles was selected on the basis of a citation-based strategy aiming to minimize bias. RESULTS: Studies on clinical and immunological outcomes (n = 63 and 48), registry-based epi research (n = 38), and randomized controlled trials (n = 35) dominated the data set. Lead US authors have signed 110 of 200 articles. The overall level of evidence was high, with 84% of level1 and -2 reports. Highest numbers of these articles were published in New England Journal of Medicine , Transplantation , and American Journal of Transplantation. Increasing trend was observed in the number of female authors in the postmillennial era (26% versus 7%). CONCLUSIONS: This study highlights important trends in RT research of the past half-century. This bibliometric perspective identifies the most intensively researched areas and shift of research interests over time; however, it also describes important imbalances in distribution of academic prolificacy based on topic, geographical aspects, and gender.

Diagnosis and management of pancreatic insufficiency in patients with gastrectomy due to cancer or gastric ulcers: a virtual roundtable expert discussion.

INTRODUCTION: Pancreatic exocrine insufficiency (PEI) is common after gastric resection for cancer or ulcers but is under-recognized and undertreated. Although pancreatic enzyme replacement therapy (PERT) is the mainstay of PEI management, robust evidence supporting its use after gastric surgery is limited. AREAS COVERED: In the absence of guideline recommendations specific for patients with pancreatic insufficiency after gastrectomy, a panel of experts from different geographical regions convened in a virtual meeting to discuss their approach to patient management. EXPERT OPINION: Pancreatic insufficiency after gastrointestinal surgery is not a simple post-surgical complication as several factors contribute to its development. Although the pancreas is unimpaired after gastrectomy, it cannot function normally in the altered environment. Pancreatic insufficiency can be challenging to diagnose in gastrectomy patients due to nonspecific symptoms and the absence of a simple diagnostic test. Fecal elastase appears to be the default test, although it is not sufficiently sensitive nor reliable for diagnosing or monitoring PEI. Patients with maldigestion symptoms after gastrectomy are treated pragmatically: those with clinical suspicion of pancreatic insufficiency receive a trial of PERT and are monitored for symptom improvement. There is a clear need for high-quality evidence from clinical trials to guide the management of this patient population.

Use of virtual reality in port implantation to reduce perioperative anxiety and pain: protocol for a randomised controlled pilot trial at a single German university hospital (VIP-trial; DRKS00028508).

INTRODUCTION: Intravenous access port implantation is commonly performed under local anaesthesia, which offers advantages such as increased patient satisfaction and resource savings compared with general anaesthesia. However, patients may experience increased perioperative stress and anxiety in the operating room setting without general anaesthesia. Virtual reality (VR) distraction or hypnosis during surgery under local anaesthesia may help patients to auditorily and visually separate from their real environment and engage with a virtual environment through hypnorelaxing guidance. Previous studies suggested that VR hypnosedation may reduce the use of sedatives or general anaesthesia, and may offer additional benefits such as reducing postoperative pain and nausea, and promoting faster patient discharge. METHODS AND ANALYSIS: The VIP trial is a randomised controlled pilot trial comparing the usage of VR during port implantation with the current standard of care (local anaesthesia and analgosedation if needed). A total of 120 adult patients are included after screening for eligibility and obtaining informed consent. Patients are randomised preoperatively in a 1:1 ratio to the trial groups. The main outcomes are change of perioperative anxiety and pain. Further outcomes include patient satisfaction and tolerability, perioperative analgesia and sedation, occurrence of postoperative nausea, vomiting and VR sickness symptoms, surgeon's satisfaction, procedure duration, postoperative complications until postoperative day 30 and patient willingness to hypothetically undergo port implantation again under the same conditions. ETHICS AND DISSEMINATION: The VIP trial has been approved by the Ethics Committee of the Medical Faculty of Ulm University (reference number 03/22). If the intervention demonstrates that VR can effectively reduce perioperative anxiety and pain, it may become a novel standard of care to minimise the need for analgosedation or general anaesthesia in port implantation procedures and improve patient outcomes. The results will be submitted to a peer-reviewed journal in the field and will be presented at applicable conferences to ensure rigorous evaluation and access for the academic community. TRIAL REGISTRATION NUMBER: German Clinical Trials Register: DRKS00028508; registration date 15 March 2022; Universal Trial Number: U1111-1275-4995.

Supporting SURgery with GEriatric Co-Management and AI (SURGE-Ahead): A study protocol for the development of a digital geriatrician.

INTRODUCTION: Geriatric co-management is known to improve treatment of older adults in various clinical settings, however, widespread application of the concept is limited due to restricted resources. Digitalization may offer options to overcome these shortages by providing structured, relevant information and decision support tools for medical professionals. We present the SURGE-Ahead project (Supporting SURgery with GEriatric co-management and Artificial Intelligence) addressing this challenge. METHODS: A digital application with a dashboard-style user interface will be developed, displaying 1) evidence-based recommendations for geriatric co-management and 2) artificial intelligence-enhanced suggestions for continuity of care (COC) decisions. The development and implementation of the SURGE-Ahead application (SAA) will follow the Medical research council framework for complex medical interventions. In the development phase a minimum geriatric data set (MGDS) will be defined that combines parametrized information from the hospital information system with a concise assessment battery and sensor data. Two literature reviews will be conducted to create an evidence base for co-management and COC suggestions that will be used to display guideline-compliant recommendations. Principles of machine learning will be used for further data processing and COC proposals for the postoperative course. In an observational and AI-development study, data will be collected in three surgical departments of a University Hospital (trauma surgery, general and visceral surgery, urology) for AI-training, feasibility testing of the MGDS and identification of co-management needs. Usability will be tested in a workshop with potential users. During a subsequent project phase, the SAA will be tested and evaluated in clinical routine, allowing its further improvement through an iterative process. DISCUSSION: The outline offers insights into a novel and comprehensive project that combines geriatric co-management with digital support tools to improve inpatient surgical care and continuity of care of older adults. TRIAL REGISTRATION: German clinical trials registry (Deutsches Register für klinische Studien, DRKS00030684), registered on 21st November 2022.

Carbapenem Antibiotics Versus Other Antibiotics for Complicated Intra-abdominal Infections: a Systematic Review and Patient-Level Meta-analysis of Randomized Controlled Trials (PROSPERO CRD42018108854).

BACKGROUND: The treatment of complicated intra-abdominal infections remains a challenge. Both optimal medical and surgical therapy (i.e., source control) are needed to achieve low mortality and morbidity. The objective of this systematic review and meta-analysis is to determine the impact of carbapenem antibiotic therapy compared to other antibiotics in complicated intra-abdominal infections (secondary peritonitis) with an emphasis on mortality and postoperative complications. METHODS: A systematic literature search from PubMed/Medline and Web of Science databases was carried out. The last search was conducted in August 2022. PRISMA guidelines were followed. Pre-defined outcomes were mortality, treatment success, treatment failure, and adverse events. RESULTS: Ten randomized controlled trials, published from 1983 to 2013 with a total of 2377 patients (1255 patients in the carbapenem antibiotics group and 1122 in the control group), were identified. A meta-analysis comparing patients undergoing carbapenem antibiotic therapy and patients receiving other antibiotics was performed. No significant difference regarding mortality (OR 1.19, 95% CI [0.79; 1.82], p = 0.40), treatment success (OR 1.17, 95% CI [0.72; 1.91], p = 0.53), and treatment failure (OR 0.84, 95% CI [0.48; 1.45], p = 0.52) was observed. Carbapenem therapy was associated with fewer adverse events compared to therapy with other antibiotics (OR 0.79, 95% CI [0.65; 0.97], p = 0.022). CONCLUSION: There is currently no evidence that carbapenem antibiotics are superior in terms of mortality, and success or failure for the treatment of complicated intra-abdominal infections (secondary peritonitis). The rate of adverse events is lower under carbapenem therapy compared to control antibiotics. TRIAL REGISTRATION: PROSPERO 2018 CRD42018108854.

[Treatment concepts for hepatic echinococcosis]. / Therapiekonzepte bei hepatischer Echinokokkose.

The incidence of both cystic (CE) and alveolar echinococcosis (AE) is increasing in Germany. The CE can often be managed with drug treatment and interventional strategies. In contrast, AE shows characteristics of a malignant disease with a high morbidity and mortality. Benzimidazoles are potent drugs for both entities but with the necessity for a lifelong follow-up and the risk of side effects as well as progression under treatment. Therefore, the indications for surgical resection have to be carefully considered; however, the combination of drug treatment and surgery is the only curative approach. Recently, the use of minimally invasive surgery with reduced morbidity and mortality has justified surgical resection for a broader set of patients; however, minimally invasive surgery requires a high level of expertise and optimal perioperative planning. Therefore, treatment strategies, especially for AE require an individual stratified risk-benefit assessment in an interdisciplinary consensus.

Impact of perioperative steroid administration in patients undergoing elective liver resection: meta-analysis.

BACKGROUND: Perioperative steroid administration may improve postoperative outcomes in major abdominal surgery by reducing the systemic inflammatory response. The aim of this systematic review was to evaluate the impact of perioperative steroid administration on outcomes after elective liver resection. METHODS: PubMed, Cochrane Library, and Web of Science were systematically searched for randomized clinical trials (RCTs) comparing perioperative steroid administration with placebo, standard of care, or no steroids with respect to postoperative outcomes, particularly postoperative complications. Two independent reviewers critically appraised the studies and extracted data. Meta-analyses were performed using a random-effects model with ORs calculated for dichotomous outcomes and mean differences (MDs) for continuous outcomes. RESULTS: Ten RCTs comprising 930 patients were included. Perioperative steroid administration significantly reduced the overall postoperative complication rate (OR 0.61, 95 per cent c.i. 0.43 to 0.87; P = 0.006; I2 = 26 per cent). No significant differences were shown for individual complications. Several postoperative laboratory parameters were positively affected, like total serum bilirubin (MD -0.46; 95 per cent c.i. -0.74 to -0.18; P = 0.001; I2 = 80 per cent), interleukin 6 (MD -48.99; 95 per cent c.i. -60.72 to -37.27; P < 0.001; I2 = 0 per cent) and C-reactive protein (MD -5.20; 95 per cent c.i. -7.62 to -2.77; P < 0.001; I2 = 71 per cent). There were no signs of an increase in potential steroid-induced adverse events, namely infectious complications, thromboembolic events, or bleeding. CONCLUSIONS: Perioperative steroid administration significantly reduces the overall complication rate after elective liver resection without an increased risk of adverse effects.