A novel clinical brain prognostic index for KRAS-mutated lung cancer and brain metastases (KRAS-BPI): Real-world evidence from two large European centers.

Introduction: Several prognostic scores were developed for non-small-cell lung cancer (NSCLC) patients with brain metastases (BM), though limited data reported for the KRAS-mutated subgroup. KRAS-targeted therapies have improved extracranial and intracranial response, highlighting the need for reliable prognostic biomarkers.

Methods: A retrospective cohort (2010-2020) comprising 220 patients with BM KRAS-mutated NSCLC from two large academic Thoracic Oncology centers (Karolinska and Heidelberg) was analyzed.

Treatment of metastatic ALK-positive non-small cell lung cancer: real-world outcomes in a single center study.

Background: Rearrangement in anaplastic lymphoma kinase () occurs in 4-7% of non-small cell lung cancer (NSCLC) cases. Despite improved survival with tyrosine kinase inhibitors (TKIs), treatment resistance remains challenging. This retrospective study analyzed advanced ALK-positive NSCLC patients, focusing on clinical aspects, treatments, resistance, and outcomes.

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.

From morbidity reduction to cost-effectiveness: Enhanced recovery after surgery (ERAS) society recommendations in minimal invasive liver surgery.

Purpose: Minimal-invasive liver surgery (MILS) reduces surgical trauma and is associated with fewer postoperative complications. To amplify these benefits, perioperative multimodal concepts like Enhanced Recovery after Surgery (ERAS), can play a crucial role. We aimed to evaluate the cost-effectiveness for MILS in an ERAS program, considering the necessary additional workforce and associated expenses.

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.

Impact of complexity in minimally invasive liver surgery on enhanced recovery measures: prospective study.

Background: Adherence to enhanced recovery after surgery (ERAS) protocols is crucial for successful liver surgery. The aim of this study was to assess the impact of minimally invasive liver surgery complexity on adherence after implementing an ERAS protocol.

Methods: Between July 2018 and August 2021, a prospective observational study involving minimally invasive liver surgery patients was conducted.

Patient with a novel syndrome with multiple benign hepatic lesions and extrahepatic neoplasms.

Simultaneous occurrence of benign hepatic lesions of different types is a sporadic phenomenon. To the best of our knowledge, we report the first clinical case of a syndrome with simultaneous manifestations of three different entities of benign liver tumors (hepatocellular adenoma, focal nodular hyperplasia and hemangioma) with a novel mutation detected in the liver adenoma and in the presence of a number of further extrahepatic organ neoplasms. Furthermore, we describe for the first time the presence of liver epithelial cells of hepatocytic phenotype expressing cytokeratin 7 (CK7) at the border of the adenoma.

Validation of the ALK-Brain Prognostic Index for patients with ALK-rearranged lung cancer and brain metastases.

Background: Brain metastases (BMs) are a key challenge in the management of anaplastic lymphoma kinase-rearranged non-small-cell lung cancer (ALK+ NSCLC), but prognostic scores are complicated or rely on data before the era of tyrosine kinase inhibitors (TKIs). This study aimed to validate the novel ALK-Brain Prognostic Index (ALK-BPI), which was originally proposed based on 44 TKI-treated ALK+ NSCLC patients from Karolinska University Hospital, using an external clinical cohort.

Patients And Methods: TKI-treated ALK+ NSCLC patients with BM from Heidelberg (n = 82, cohort 1) were retrospectively analyzed alone and together with the original Karolinska cohort (n = 126, cohort 2).

Concordance of a decision algorithm and multidisciplinary team meetings for patients with liver cancer-a study protocol for a randomized controlled trial.

Introduction: Multidisciplinary team meetings (MDMs), also known as tumor conferences, are a cornerstone of cancer treatments. However, barriers such as incomplete patient information or logistical challenges can postpone tumor board decisions and delay patient treatment, potentially affecting clinical outcomes. Therapeutic Assistance and Decision algorithms for hepatobiliary tumor Boards (ADBoard) aims to reduce this delay by providing automated data extraction and high-quality, evidence-based treatment recommendations.

Sensing Acute Cellular Rejection in Liver Transplant Patients Using Liver-Derived Extracellular Particles: A Prospective, Observational Study.

Acute cellular rejection (ACR) after liver transplantation (LT) goes along with allograft dysfunction, which is diagnosed by liver biopsy and concomitant histological analysis, representing the gold standard in clinical practice. Yet, liver biopsies are invasive, costly, time-intensive and require expert knowledge. Herein we present substantial evidence that blood plasma residing peripheral liver-derived extracellular particles (EP) could be employed to diagnose ACR non-invasively.

Multiplex immune protein profiling of fine-needle aspirates from patients with non-small-cell lung cancer reveals signatures associated with PD-L1 expression and tumor stage.

Biomarker signatures identified through minimally invasive procedures already at diagnosis of non-small-cell lung cancer (NSCLC) could help to guide treatment with immune checkpoint inhibitors (ICI). Here, we performed multiplex profiling of immune-related proteins in fine-needle aspirate (FNA) samples of thoracic lesions from patients with NSCLC to assess PD-L1 expression and identify related protein signatures. Transthoracic FNA samples from 14 patients were subjected to multiplex antibody-based profiling by proximity extension assay (PEA).

Detection of Tumor-Associated Membrane Receptors on Extracellular Vesicles from Non-Small Cell Lung Cancer Patients via Immuno-PCR.

Precision cancer medicine for non-small-cell lung cancer (NSCLC) has increased patient survival. Nevertheless, targeted agents towards tumor-associated membrane receptors only result in partial remission for a limited time, calling for approaches which allow longitudinal treatment monitoring. Rebiopsy of tumors in the lung is challenging, and metastatic lesions may have heterogeneous signaling.

Extended liver resection in mice: state of the art and pitfalls-a systematic review.

Background: Rodent models of liver resection have been used to investigate and evaluate the liver's complex physiology and pathology since 1931. First documented by Higgins and Anderson, such models were created to understand liver regeneration mechanisms to improve outcomes in patients undergoing extensive liver resection for liver cancer or other underlying liver diseases.

Methods: A systematic search was conducted using Pubmed, gathering publications up to January 2019, which engaged with the mouse model of extended liver resection as a method itself.

ALK-Brain Prognostic Index-Preliminary Study of a Prognostic Tool for Patients with ALK-Rearranged, Non-small Cell Lung Cancer and Brain Metastases.

Background: Disease-specific Graded Prognostic Assessment (DS-GPA) is the most validated prognostic tool for patients with brain metastasized lung cancer. The Lung-molGPA scoring system was recently introduced for oncogenic-driven brain metastasized lung cancer, but has not yet been validated in cohorts including only ALK-translocated tumors.

Methods: We designed a retrospective cohort study consisting of 44 patients with brain metastasized ALK-positive, non-small cell lung cancer (NSCLC) who were treated between January 2009 and November 2019 at Karolinska University Hospital in Stockholm, Sweden.

Increased Cell-Free DNA Plasma Concentration Following Liver Transplantation Is Linked to Portal Hepatitis and Inferior Survival.

Donor organ quality is crucial for transplant survival and long-term survival of patients after liver transplantation. Besides bacterial and viral infections, endogenous damage-associated molecular patterns (DAMPs) can stimulate immune responses. Cell-free DNA (cfDNA) is one such DAMP that exhibits highly proinflammatory effects via DNA sensors.

Laparoscopic Versus Open Liver Resection for Benign Tumors and Lesions: A Case Matched Study with Propensity Score Matching.

In recent years, minimally invasive surgical approaches have gained an increasingly important role in hepatobiliary surgery. The aim of this study was to investigate the safety and potential benefits of laparoscopic liver resection (LLR) compared with open liver resection (OLR) for benign liver tumors and lesions. Between January 2009 and December 2017, 182 patients underwent liver resection for benign liver tumors and lesions at our center.

Human Stem Cells Promote Liver Regeneration After Partial Hepatectomy in BALB/C Nude Mice.

Background: Mesenchymal stem cells (MSCs) have been suggested to augment liver regeneration after surgically and pharmacologically induced liver failure. To further investigate this we processed human bone marrow-derived MSC according to good manufacturing practice (GMP) and tested those cells for their modulatory capacities of metabolic alterations and liver regeneration after partial hepatectomy in BALB/c nude mice.

Methods: Human MSCs were obtained by bone marrow aspiration of healthy donors as in a previously described GMP process.

The nanomolar sensing of nicotinamide adenine dinucleotide in human plasma using a cycling assay in albumin modified simulated body fluids.

Nicotinamide adenine dinucleotide (NAD), a prominent member of the pyridine nucleotide family, plays a pivotal role in cell-oxidation protection, DNA repair, cell signalling and central metabolic pathways, such as beta oxidation, glycolysis and the citric acid cycle. In particular, extracellular NAD has recently been demonstrated to moderate pathogenesis of multiple systemic diseases as well as aging. Herein we present an assaying method, that serves to quantify extracellular NAD in human heparinised plasma and exhibits a sensitivity ranging from the low micromolar into the low nanomolar domain.

Validity of the Iwate criteria for patients with hepatocellular carcinoma undergoing minimally invasive liver resection.

Background: Recently proposed by the International Consensus Conference on Laparoscopic Liver Resection, the Iwate criteria (IC) can be used by surgeons to predict the operative difficulty of laparoscopic liver resection (LLR) and were validated in patients with hepatocellular carcinoma (HCC), the most common indication for LLR.

Methods: The IC comprise six preoperative factors that allow the grading of operative difficulty as low, intermediate, advanced, or expert. IC scores were validated in patients with HCC who underwent LLR (n = 77).