Extracellular vesicles as potential biomarkers for diagnosis and recurrence detection of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and a leading cause of cancer-related deaths worldwide. However, current diagnostic tools are often invasive and technically limited. In the last decade, non-invasive liquid biopsies have transformed the field of clinical oncology, showcasing the potential of various liquid-biopsy derived analytes, including extracellular vesicles (EVs), to diagnose and monitor HCC progression and metastatic spreading, serving as promising novel biomarkers. A prospective single-center cohort study including 37 HCC patients and 20 patients with non-malignant liver disease (NMLD), as a control group, was conducted. Serum EVs of both groups were analyzed before and after liver surgery. The study utilized microbead-based magnetic particle sorting and flow cytometry to detect 37 characteristic surface proteins of EVs. Furthermore, HCC patients who experienced tumor recurrence (R-HCC) within 12 months after surgery were compared to HCC patients without recurrence (NR-HCC). EVs of R-HCC patients (n = 12/20) showed significantly lower levels of CD31 compared to EVs of NR-HCC patients (p = 0.0033). EVs of NMLD-group showed significantly higher expressions of CD41b than EVs of HCC group (p = 0.0286). The study determined significant short-term changes in CD19 dynamics in EVs of the NMLD-group, with preoperative values being significantly higher than postoperative values (p = 0.0065). This finding of our pilot study suggests EVs could play a role as potential targets for the development of diagnostic and therapeutic approaches for the early and non-invasive detection of HCC recurrence. Further, more in-depth analysis of the specific EV markers are needed to corroborate their potential role as diagnostic and therapeutic targets for HCC.

Liver failure after treatment with inotuzumab and polychemotherapy including PEG-asparaginase in a patient with relapsed Philadelphia chromosome-negative acute lymphoblastic leukemia.

We present the case of a 58-year-old female patient who presented with an extramedullary B-ALL relapse after prior allogenic HSCT and blinatumomab therapy. The patient died from complications of a drug-induced acute liver failure after a salvage therapy combining inotuzumab ozogamicin (InO)-based induction followed by consolidation with high dose MTX and pegaspargase based on the GMALL protocol for older ALL patients. After a diagnosis of the extramedullary relapse in the form of a retro vesical chloroma, the patient received an individualized multi-agent chemotherapy based on induction chemotherapy for older patients in combination with InO. After four administrations of InO, in combination with vincristine, dexamethasone, cytarabine, and cyclophosphamide, CT-imaging showed a reduction in volume of the chloroma and response to therapy. Consolidation with high-dose methotrexate and pegaspargase was administered. The patient developed toxic liver damage manifested by hyperbilirubinemia and progressive hepatic encephalopathy. The diagnostic criteria for VOD were met, and therapy with defibrotide was initiated. Liver biopsy revealed no histological signs of VOD but instead steatohepatitis indicative of drug-induced toxicity. The patient ultimately died of hemorrhagic shock through postinterventional hemorrhage after liver biopsy. In conclusion, although InO shows promising results in the therapy of r/r ALL with and without additional chemotherapy, the combination with MTX and pegaspargase in an intensively pretreated patient with relapse after HCST may impart an increased risk for liver-related toxicity. Special caution is required when assessing fitness for further liver toxic regimens. A key takeaway is also the reminder that InO can cause liver damage not only in the form of VOD but also through direct hepatocellular toxicity.

[Small hepatocellular carcinoma : Diagnostics according to guidelines and established in the clinical setting]. / Das kleine hepatozelluläre Karzinom : Leitliniengerechte und klinisch etablierte Diagnostik.

CLINICAL/METHODICAL ISSUE: The diagnosis of hepatocellular carcinoma (HCC)-especially the characterization of small lesions <2 cm-continues to be a radiological challenge. STANDARD RADIOLOGICAL METHODS: In the current S3 guideline on diagnosis and therapy of HCC, contrast-enhanced imaging examinations, such as contrast-enhanced ultrasonography (CEUS), computed tomography (CT), and magnetic resonance imaging (MRI), are still the diagnostic standard. METHODOLOGICAL INNOVATIONS: HCC in the cirrhotic liver should be diagnosed by its typical contrast-enhanced pattern in the MRI. In addition, the use of quality assurance instruments such as LI-RADS (Liver Imaging Reporting and Data System) contributes to the desired consistency of findings, even with small ambiguous findings. PERFORMANCE: Many studies have shown that the LI-RADS classification reflects the likelihood of HCC and other malignant liver lesions. ACHIEVEMENTS: Guidelines and quality assurance instruments contribute to a more precise diagnosis in patients with suspected HCC. PRACTICAL RECOMMENDATIONS: A guideline-compliant diagnostic algorithm and the LI-RADS should be used across the board for accurate HCC diagnostics.

Quantification of COVID-19 Opacities on Chest CT - Evaluation of a Fully Automatic AI-approach to Noninvasively Differentiate Critical Versus Noncritical Patients.

OBJECTIVES: To evaluate the potential of a fully automatic artificial intelligence (AI)-driven computed tomography (CT) software prototype to quantify severity of COVID-19 infection on chest CT in relationship with clinical and laboratory data. METHODS: We retrospectively analyzed 50 patients with laboratory confirmed COVID-19 infection who had received chest CT between March and July 2020. Pulmonary opacifications were automatically evaluated by an AI-driven software and correlated with clinical and laboratory parameters using Spearman-Rho and linear regression analysis. We divided the patients into sub cohorts with or without necessity of intensive care unit (ICU) treatment. Sub cohort differences were evaluated employing Wilcoxon-Mann-Whitney-Test. RESULTS: We included 50 CT examinations (mean age, 57.24 years), of whom 24 (48%) had an ICU stay. Extent of COVID-19 like opacities on chest CT showed correlations (all p < 0.001 if not otherwise stated) with occurrence of ICU stay (R = 0.74), length of ICU stay (R = 0.81), lethal outcome (R = 0.56) and length of hospital stay (R = 0.33, p < 0.05). The opacities extent was correlated with laboratory parameters: neutrophil count (NEU) (R = 0.60), lactate dehydrogenase (LDH) (R = 0.60), troponin (TNTHS) (R = 0.55) and c-reactive protein (CRP) (R = 0.51). Differences (p < 0.001) between ICU group and non-ICU group concerned longer length of hospital stay (24.04 vs. 10.92 days), higher opacity score (12.50 vs. 4.96) and severity of laboratory data changes such as c-reactive protein (11.64 vs. 5.07 mg/dl, p < 0.01). CONCLUSIONS: Automatically AI-driven quantification of opacities on chest CT correlates with laboratory and clinical data in patients with confirmed COVID-19 infection and may serve as non-invasive predictive marker for clinical course of COVID-19.

Characterization of Severe Arterial Phase Respiratory Motion Artifact on Gadoxetate Disodium-Enhanced MRI - Assessment of Interrater Agreement and Reliability.

PURPOSE: To assess the interrater agreement and reliability of experienced abdominal radiologists in the characterization and grading of arterial phase gadoxetate disodium-related respiratory motion artifact on liver MRI. MATERIALS AND METHODS: This prospective multicenter study was initiated by the working group for abdominal imaging within the German Roentgen Society (DRG), and approved by the local IRB of each participating center. 11 board-certified radiologists independently reviewed 40 gadoxetate disodium-enhanced liver MRI datasets. Motion artifacts in the arterial phase were assessed on a 5-point scale. Interrater agreement and reliability were calculated using the intraclass correlation coefficient (ICC) and Kendall coefficient of concordance (W), with p < 0.05 deemed significant. RESULTS: The ICC for interrater agreement and reliability were 0.983 (CI 0.973 - 0.990) and 0.985 (CI 0.978 - 0.991), respectively (both p < 0.0001), indicating excellent agreement and reliability. Kendall's W for interrater agreement was 0.865. A severe motion artifact, defined as a mean motion score ≥ 4 in the arterial phase was observed in 12 patients. In these specific cases, a motion score ≥ 4 was assigned by all readers in 75 % (n = 9/12 cases). CONCLUSION: Differentiation and grading of arterial phase respiratory motion artifact is possible with a high level of inter-/intrarater agreement and interrater reliability, which is crucial for assessing the incidence of this phenomenon in larger multicenter studies. KEY POINTS: · Inter- and intrarater agreement for motion artifact scoring is excellent among experienced readers.. · Interrater reliability for motion artifact scoring is excellent among experienced readers.. · Characterization of severe motion artifacts proved feasible in this multicenter study.. CITATION FORMAT: · Ringe KI, Luetkens JA, Fimmers R et al. Characterization of Severe Arterial Phase Respiratory Motion Artifact on Gadoxetate Disodium-Enhanced MRI - Assessment of Interrater Agreement and Reliability. Fortschr Röntgenstr 2017; 190: 341 - 347.