Publications by authors named "Gruenberger T"

Background: Major hepatectomy in perihilar cholangiocarcinoma (pCCA) patients with a small future liver remnant (FLR) risks posthepatectomy liver failure (PHLF). This study examines combined portal and hepatic vein embolisation (PVE/HVE) to increase preoperative FLR volume and potentially decrease PHLF rates.

Methods: In this retrospective, multicentre, observational study, data was collected from centres affiliated with the DRAGON Trials Collaborative and the EuroLVD registry.

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Liver resection (LR) is the primary treatment for hepatic tumors, yet posthepatectomy liver failure (PHLF) remains a significant concern. While the precise etiology of PHLF remains elusive, dysregulated inflammatory processes are pivotal. Therefore, we explored the theragnostic potential of extracellular high-mobility-group-box protein 1 (HMGB1), a key damage-associated molecular pattern (DAMP) released by hepatocytes, in liver recovery post LR in patients and animal models.

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Article Synopsis
  • The study investigates the use of von Willebrand factor antigen (vWF-Ag) as a non-invasive biomarker to assess complications related to portal hypertension and predict patient outcomes in hepatocellular carcinoma (HCC) after liver resection.
  • The research found that vWF-Ag levels were strongly linked to time to recurrence and overall survival, with specific cutoff values indicating significant risk for posthepatectomy liver failure (PHLF) and clinically significant portal hypertension (CSPH).
  • Results suggest that measuring vWF-Ag could enhance preoperative risk assessment for patients with resectable HCC, potentially guiding treatment decisions based on identified risk levels.
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The activation of the receptor tyrosine kinase Axl by Gas6 is a major driver of tumorigenesis. Despite recent insights, tumor cell-intrinsic and -extrinsic Axl functions are poorly understood in hepatocellular carcinoma (HCC). Thus, we analyzed the cell-specific aspects of Axl in liver cancer cells and in the tumor microenvironment.

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Due to the fact biliary tract cancer (BTC) is often diagnosed at an advanced stage, thus, not eligible for resection, and due to the aggressive tumor biology, it is considered as one of the cancer types with the worst prognosis. Advances in diagnosis, surgical techniques, and molecular characterization have led to an improvement of the prognosis of BTC patients, recently. Although neoadjuvant therapy is expected to improve surgical outcomes by reducing tumor size, its routine is not well established.

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In 2007, the ASSO-LM1 trial, a multicenter prospective study, was initiated to investigate the resectability (R0) rate following preoperative combination therapy with XELOX and bevacizumab in patients with potentially resectable colorectal liver metastases. Six cycles of systemic therapy were administered preoperatively, although the sixth cycle did not include bevacizumab, resulting in 5 weeks between the last bevacizumab dose and surgery. Treatment with bevacizumab plus XELOX was restarted for another six cycles postoperatively.

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  • Posthepatectomy liver failure (PHLF) is a major cause of short-term death after liver surgery, and this study evaluates the effectiveness of two liver function tests: APRI+ALBI and LiMAx.
  • The study analyzed 352 patients from four European centers, comparing the predictive potential of both tests for significant PHLF and 90-day mortality using statistical methods.
  • Results showed that APRI+ALBI was more effective than LiMAx in predicting PHLF grades B and C as well as 90-day mortality, and it was also less costly and less labor-intensive.
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Background: There is a lack of consensus on the definition of upfront resectability and use of perioperative systemic therapy for colorectal liver metastases (CRLM). This survey aimed to summarize the current treatment strategies for upfront resectable CRLM throughout Europe.

Methods: A survey was sent to all members of the European-African Hepato-Pancreato-Biliary Association to gain insight into the current views on resectability and the use of systemic therapy for upfront resectable CRLM.

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Background: Posthepatectomy liver failure (PHLF) represents a life-threatening complication with limited therapeutic options. Neutrophils play a critical and dynamic role during regeneratory processes, but their role in human liver regeneration is incompletely understood, especially as underlying liver disease, detectable in the majority of patients, critically affects hepatic regeneration. Here we explored intrahepatic neutrophil accumulation and neutrophil extracellular traps (NETs) in patients with PHLF and validated the functional relevance of NETs in a murine partial hepatectomy (PHx) model.

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Objective And Background: Clinically significant posthepatectomy liver failure (PHLF B+C) remains the main cause of mortality after major hepatic resection. This study aimed to establish an APRI+ALBI, aspartate aminotransferase to platelet ratio (APRI) combined with albumin-bilirubin grade (ALBI), based multivariable model (MVM) to predict PHLF and compare its performance to indocyanine green clearance (ICG-R15 or ICG-PDR) and albumin-ICG evaluation (ALICE).

Methods: 12,056 patients from the National Surgical Quality Improvement Program (NSQIP) database were used to generate a MVM to predict PHLF B+C.

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Aim: Multidisciplinary management of metastatic colorectal liver metastases (CRLM) is still challenging. To assess postoperative complications in initially unresectable or borderline resectable CRLM, the prospective EORTC-1409 ESSO 01-CLIMB trial capturing 'real-life data' of European centres specialized in liver surgery was initiated.

Material And Methods: A total of 219 patients were registered between May 2015 and January 2019 from 15 centres in nine countries.

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Locally advanced or metastatic cholangiocarcinoma is an aggressive carcinoma with a dismal prognosis. For the first-line treatment of locally advanced or metastatic cholangiocarcinoma, cisplatin/gemcitabine has been the standard of care for more than 10 years. Its combination with the immune checkpoint inhibitor durvalumab resulted in an efficiency improvement in the phase III setting.

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Background: Twenty percent of colorectal cancer liver metastases (CLMs) are initially resectable with a 5-year survival rate of 25%-40%. Perioperative folinic acid, 5-fluorouracil, oxaliplatin (FOLFOX) increases progression-free survival (PFS). In advanced disease, the addition of targeting therapies results in an overall survival (OS) advantage.

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Background: Posthepatectomy liver failure (PHLF) contributes significantly to morbidity and mortality after liver surgery. Standardized assessment of preoperative liver function is crucial to identify patients at risk. These European consensus guidelines provide guidance for preoperative patient assessment.

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The expression of the receptor tyrosine kinase Axl and its cleavage product soluble Axl (sAxl) is increased in liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). In this multicenter study, we evaluated the diagnostic value of Gas6, the high-affinity ligand of Axl, in patients with chronic liver disease. Levels of sAxl and Gas6, and their albumin (alb) ratios were analyzed in serum samples of patients with biopsy-proven liver fibrosis, end-stage liver disease, HCC, and healthy controls, and were compared to Fibrosis-4 (FIB-4), enhanced liver fibrosis (ELF™) test, Child-Pugh score (CPS), model of end-stage liver disease (MELD) score, hepatic venous pressure gradient, and α-fetoprotein, respectively.

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Article Synopsis
  • This project developed a framework for managing patients with synchronous colorectal cancer and liver metastases, addressing terminology, diagnosis, and treatment strategies.* -
  • A multi-organizational consensus was reached through a Delphi process, resulting in twelve key statements with at least 70% agreement on issues like treatment pathways and tumor board composition.* -
  • Key findings include definitions for metastases timing, guidelines for clinical assessments, and recommendations for various treatment approaches, aimed at improving clinical practice for affected patients.*
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Background: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases, with a focus on terminology, diagnosis, and management.

Methods: This project was a multiorganizational, multidisciplinary consensus.

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(1) Background: The pathological tumor response of the primary tumor to induction chemotherapy in synchronously metastasized colorectal cancer (mCRC) patients has not been investigated. The aim of this study was to compare patients treated with induction chemotherapy combined with vascular endothelial growth factor (VEGF) or with epidermal growth factor receptor (EGFR) antibodies. (2) Methods: We present a retrospective analysis, where we included 60 consecutive patients with potentially resectable synchronous mCRC who received induction chemotherapy combined with either VEGF or EGFR antibodies.

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This article summarises expert discussion on the management of patients with hepatocellular carcinoma (HCC), which took place during the 24th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, July 2022. A multidisciplinary approach is mandatory to ensure an optimal diagnosis and staging of HCC, planning of curative and therapeutic options, including surgical, embolisation, ablative strategies, or systemic therapy. Furthermore, in many patients with HCC, underlying liver cirrhosis represents a challenge and influences the therapeutic options.

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  • The study investigates early transcriptional changes in human liver regeneration and how underlying liver diseases affect this process.
  • Researchers analyzed blood and tissue samples from patients undergoing liver surgery, focusing on those with dysfunctional liver regeneration.
  • Results showed that patients with dysfunctional regeneration exhibited heightened inflammatory responses and reduced expression of a critical gene (DUSP4) linked to adhesion molecule regulation, potentially hindering effective liver recovery.
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  • * It was found that YAP-1 levels increased shortly after the onset of LR and that specific deletion of YAP-1 in biliary epithelial cells (BECs) impaired LR in mice.
  • * The research indicates that serotonin promotes YAP-1 activation through tyrosine phosphorylation in BECs, leading to increased osteopontin (OPN) expression and supporting liver regeneration.
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  • Activin A plays a crucial role in liver regeneration, but its effects on humans after liver surgery are not well studied, prompting this research on its predictive value for posthepatectomy liver failure (PHLF).
  • The study tested levels of activin A and its antagonist FSTL-3 in 59 patients undergoing liver surgery and found significant changes in their individual levels post-surgery, but not in their ratio.
  • The activin A/FSTL-3 ratio was a strong predictor for PHLF and related complications, suggesting its use in preoperative evaluations, although further research is needed for confirmation.
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The colorectal cancer (CRC) screening program B-PREDICT is an invited two-stage screening project using a fecal immunochemical test (FIT) for initial screening followed by a colonoscopy for those with a positive FIT. Since the gut microbiome likely plays a role in the etiology of CRC, microbiome-based biomarkers in combination with FIT could be a promising tool for optimizing CRC screening. Therefore, we evaluated the usability of FIT cartridges for microbiome analysis and compared it to Stool Collection and Preservation Tubes.

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Background & Aims: Surgical resection of the cancerous tissue represents one of the few curative treatment options for neoplastic liver disease. Such partial hepatectomy (PHx) induces hepatocyte hyperplasia, which restores liver function. PHx is associated with bacterial translocation, leading to an immediate immune response involving neutrophils and macrophages, which are indispensable for the priming phase of liver regeneration.

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