Treatment with gemcitabine/cisplatin and durvalumab for advanced biliary tract cancer - real-world data from a multicenter German patient population.

Background: Biliary tract cancers (BTCs) are a heterogeneous group of malignant cancers with an overall poor prognosis. For more than a decade, the standard palliative first-line therapy was cytotoxic chemotherapy with gemcitabine/cisplatin. The results of the TOPAZ-1 and KEYNOTE-966 trials have now introduced immune checkpoint inhibitors (ICIs) into first-line therapy.

Soluble Urokinase Plasminogen Activator Receptor Predicts Survival and Hepatic Decompensation in Advanced Hepatocellular Carcinoma.

Background And Aims: The introduction of immune checkpoint inhibitor (ICI) based therapies has significantly improved the prognosis of patients with unresectable hepatocellular carcinoma (HCC). However, the variable treatment response and the uncertain benefit in patients with advanced liver cirrhosis emphasise the urgent need for prognostic and predictive biomarkers guiding patient selection. The soluble urokinase plasminogen activator receptor (suPAR) is strongly associated with inflammation, liver cirrhosis and various types of cancer.

Development of Liver-Heart Score for Early Detection of Myocardial Contractile Dysfunction in Cirrhosis by Strain Imaging.

Aim: Cirrhotic cardiomyopathy is characterised by myocardial dysfunction in patients with cirrhosis in the absence of other cardiac conditions. We aimed to develop and validate a scoring system to identify patients at high risk for reduced global longitudinal strain, a newly proposed marker of myocardial dysfunction in the updated diagnostic criteria for cirrhotic cardiomyopathy.

Methods: Prospectively recruited patients with cirrhosis in the training and validation groups underwent identical hepatological and cardiological evaluations, including strain echocardiography.

Evaluation of prognostic scores in patients with HCC undergoing first-line immunotherapy with atezolizumab and bevacizumab.

Background & Aims: Immunotherapy with atezolizumab and bevacizumab (a + b) has improved the prognosis of patients with unresectable hepatocellular carcinoma (HCC). However, the outcome for individual patients is highly variable. This study aimed to (i) develop and validate a prognostic prediction model to estimate individual prognosis and (ii) compare it with established models.

CT-guided high-dose-rate brachytherapy ablation of HCC patients with portal vein tumor thrombosis.

Background: We assessed the safety and efficacy of computed tomography (CT)-guided high-dose-rate (HDR) brachytherapy in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT).

Methods: From January 2010 to January 2022, 56 patients (median age 67.5 years) with HCC and PVTT underwent 64 procedures.

miR-223 and Chromogranin A Affect Inflammatory Immune Cell Activation in Liver Metastasis of Neuroendocrine Neoplasms.

Neuroendocrine neoplasms (NENs) are a diverse group originating from endocrine cells/their precursors in pancreas, small intestine, or lung. The key serum marker is chromogranin A (CgA). While commonly elevated in patients with NEN, its prognostic value is still under discussion.

Single-cell RNA sequencing-derived signatures define response patterns to atezolizumab + bevacizumab in advanced hepatocellular carcinoma.

Background & Aims: The combination of atezolizumab and bevacizumab (atezo+bev) is the current standard of care for advanced hepatocellular carcinoma (HCC), providing a median overall survival (OS) of 19.2 months. Here, we aim to uncover the underlying cellular processes driving clinical benefit vs.

Extracellular Vesicles May Predict Response to Atezolizumab Plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma.

Background And Aims: Treatment with atezolizumab and bevacizumab has been approved as one of the standards of care for patients with advanced hepatocellular carcinoma (HCC). The median overall survival (OS) upon available treatments still remains below 2 years, urgently suggesting better stratification tools to identify ideal candidates for this treatment and potentially allowing personalized approaches. In this study, we evaluated the potential role of extracellular vesicles (EVs) as a novel biomarker in patients receiving atezolizumab and bevacizumab for HCC.

Extracellular NAD response to post-hepatectomy liver failure: bridging preclinical and clinical findings.

Liver fibrosis progressing to cirrhosis is a major risk factor for liver cancer, impacting surgical treatment and survival. Our study focuses on the role of extracellular nicotinamide adenine dinucleotide (eNAD) in liver fibrosis, analyzing liver disease patients undergoing surgery. Additionally, we explore NAD's therapeutic potential in a mouse model of extended liver resection and in vitro using 3D hepatocyte spheroids.

Soluble urokinase plasminogen activator receptor levels predict survival in patients with portal hypertension undergoing TIPS.

Background & Aims: Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective therapy for complications of portal hypertension. However, clinical outcomes following TIPS placement vary widely between patients and identifying ideal candidates remains a challenge. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating marker of immune activation that has previously been associated with liver inflammation, but its prognostic value in patients receiving TIPS is unknown.

Optimized protocol for quantification of extracellular nicotinamide adenine dinucleotide: evaluating clinical parameters and pre-analytical factors for translational research.

Nicotinamide adenine dinucleotide (NAD), a coenzyme for more than 500 enzymes, plays a central role in energy production, metabolism, cellular signaling, and DNA repair. Until recently, NAD was primarily considered to be an intracellular molecule (iNAD), however, its extracellular species (eNAD) has recently been discovered and has since been associated with a multitude of pathological conditions. Therefore, accurate quantification of eNAD in bodily fluids such as plasma is paramount to answer important research questions.

Immune signatures of checkpoint inhibitor-induced autoimmunity-A focus on neurotoxicity.

Background: Neurologic immune-related adverse events (irAE-n) are rare but severe toxicities of immune checkpoint inhibitor (ICI) treatment. To overcome diagnostic and therapeutic challenges, a better mechanistic understanding of irAE-n is paramount.

Methods: In this observational cohort study, we collected serum and peripheral blood samples from 34 consecutive cancer patients with irAE-n (during acute illness) and 49 cancer control patients without irAE-n (pre- and on-ICI treatment, n = 44 without high-grade irAEs, n = 5 with high-grade nonneurologic irAEs).

The Role of Alternative Lymph Node Classification Systems in Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NEN): Superiority of a LODDS Scheme Over N Category in Pancreatic NEN (pNEN).

Lymph node (LN) involvement in gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) has been reported to have prognostic and therapeutic implications. Numerous novel LN classifications exist; however, no comparison of their prognostic performance for GEP-NEN has been done yet. Using a nationwide cohort from the German Neuroendocrine Tumor (NET) Registry, the prognostic and discriminatory power of different LN ratio (LNR) and log odds of metastatic LN (LODDS) classifications were investigated using multivariate Cox regression and C-statistics in 671 patients with resected GEP-NEN.

Prevalence of and factors associated with a treatment delay due to the COVID-19 pandemic in patients with gastrointestinal cancer in Europe.

Background: Recent studies have raised the issue of delayed cancer care during the COVID-19 pandemic, but the extent of delays and cancellations in cancer treatment, screening and diagnosis varied widely by geographic region and study design, highlighting the need for further research.

Methods: We used the Oncology Dynamics (OD) database featuring data from a cross-sectional, partially retrospective survey to analyze treatment delays in 30,171 GI cancer patients from five European countries (Germany, France, UK, Spain, and Italy). Risk factors for treatment delays were identified using multivariable logistic regression models.

Non-Alcoholic Fatty Liver Disease (NAFLD) and risk of new-onset heart failure: a retrospective analysis of 173,966 patients.

Background: Non-alcoholic fatty liver disease (NAFLD) represents the leading cause of chronic liver disease. Its high mortality and morbidity are mainly caused by non-hepatic comorbidities and their clinical complications. Accumulating evidence suggests an association between NAFLD and heart failure (HF), but large-scale data analyses from Germany are scarce.

Prediction of regional lymph node metastasis in intrahepatic cholangiocarcinoma: it's not all about size.

Objectives: Lymph node metastases (LNM) are frequent in patients with intrahepatic cholangiocarcinoma (iCC) and worsen their prognosis even after surgery. Our aim was to investigate the predictive value of lymph node (LN) short axis, the most common discriminator for identifying LNM in tumor-imaging and to develop a predictive model for regional LNM in iCC taking computed tomography (CT) features of extranodal disease into account.

Materials And Methods: We enrolled 102 patients with pathologically proven iCC who underwent CT prior to hepatic resection and hilar lymph node dissection (LND) from 2005 to 2021.

Study protocol of an open-label, single arm phase II trial investigating the efficacy and safety of Trifluridine/Tipiracil combined with irinotecan as a second line therapy in patients with cholangiocarcinoma (TRITICC).

Background: The prognosis of patients with advanced biliary tract cancer (BTC) who have progressed on gemcitabine plus cisplatin is dismal. Trifluridine/tipiracil (FTD/TPI) and irinotecan have proven efficacy in different gastrointestinal malignancies. We therefore hypothesized that this combination might improve the therapeutic outcome in patients with BTC after failure of first line treatment.

Interventional Treatment Strategies in Intrahepatic Cholangiocarcinoma and Perspectives for Combined Hepatocellular-Cholangiocarcinoma.

cHCC-CCA is an uncommon type of liver cancer that exhibits clinical and pathological characteristics of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), which are the two main forms of primary liver cancer. The similarity to HCC and CCA makes therapeutical strategies challenging. The poor prognosis of CCA in general, as well as for cHCC-CCA, is mainly attributable to the fact that diagnosis is often at an advanced stage of disease.

Systemic treatment in patients with Child-Pugh B liver dysfunction and advanced hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of death among patients with liver cirrhosis. The rise of immuno-oncology has revolutionized treatment for advanced HCC. However, most pivotal randomized controlled trials have excluded patients with moderate liver dysfunction (Child-Pugh-Turcotte B), despite the high incidence of liver disease in patients with HCC at the time of diagnosis.

Gd-EOB MRI for HCC subtype differentiation in a western population according to the 5 edition of the World Health Organization classification.

Objectives: To investigate the value of gadoxetic acid (Gd-EOB)-enhanced magnetic resonance imaging (MRI) for noninvasive subtype differentiation of HCCs according to the 5 edition of the WHO Classification of Digestive System Tumors in a western population.

Methods: This retrospective study included 262 resected lesions in 240 patients with preoperative Gd-EOB-enhanced MRI. Subtypes were assigned by two pathologists.

Serum CXCL5 Detects Early Hepatocellular Carcinoma and Indicates Tumor Progression.

Chemokines or chemotactic cytokines play a pivotal role in the immune pathogenesis of liver cirrhosis and hepatocellular carcinoma (HCC). Nevertheless, comprehensive cytokine profiling data across different etiologies of liver diseases are lacking. Chemokines might serve as diagnostic and prognostic biomarkers.

Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma: Results from a German real-world cohort.

Background And Aims: Phase III trials have established atezolizumab plus bevacizumab as the novel standard of care for patients with unresectable hepatocellular carcinoma (HCC). However, these trials raised concerns regarding treatment efficacy in non-viral HCC, and it remains unclear whether combination immunotherapy is safe and effective in patients with advanced cirrhosis.

Methods: One hundred patients with unresectable HCC initiated therapy with atezolizumab plus bevacizumab at our centre between January 2020 and March 2022.