Beyond the border: the use of lenvatinib in advanced hepatocellular carcinoma after different treatment lines: a retrospective analysis.

The systemic treatment of unresectable hepatocellular carcinoma (HCC) has been improved throughout the past years. Different tyrosine kinase inhibitors (TKI) and checkpoint inhibitors have approval for first- and second-line treatment. Still, data are missing about the choice for the right agent and senseful therapy sequences. Between 2017 and 2019 we treated 149 HCC patients. From those, we identified the patients, who received lenvatinib either as a first-line treatment or in a later treatment line. We investigated seven patients retrospectively, who received lenvatinib in second, third, or fourth treatment line regarding efficacy and safety. Besides that, we compared those patients with 13 patients, who received lenvatinib as a first-line treatment regarding duration of therapy, overall survivial (OS), side effects and best response to treatment. We discovered remission (PR) showed 4/7, stable disease (SD) 2/7 and 1/7 mixed response with an overall tolerable safety profile in patients with a later line lenvatinib treatment. The duration and overall survival for therapy is similar in first- and later treatment lines with comparable results. Most side effects are moderate in each treatment line. Remarkably, on patient diagnoses with HCC (the Barcelona Clinic Liver Cancer C algorithm), who received lenvatinib in fourth line reached 67 months OD since diagnosis. We conclude, that lenvatinib could be considered as a treatment option of HCC for later treatment lines.

Diagnostic accuracy and interobserver variability of Dynamic Vascular Pattern (DVP) in primary liver malignancies - A simple semiquantitative tool for the analysis of contrast enhancement patterns.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is a valuable tool in the diagnostic approach of focal liver lesions, but occasionally subjective and observer-dependent. Semiquantitative evaluation of dynamic CEUS (DCEUS) with standardised software programmes such as Dynamic Vascular Pattern (DVP) could help to improve diagnostic accuracy and objectivity in liver tumour assessment. OBJECTIVES: The present study aimed at evaluation of diagnostic accuracy of DVP in a clinical setting. MATERIALS AND METHODS: DVP images of 52 focal liver lesions [30 hepatocellular carcinomas (HCCs), 15 intrahepatic cholangiocellular carcinomas (ICCs), 7 focal nodular hyperplasias (FNHs)] were analysed by four blinded observers with different levels of CEUS-experience. Diagnostic accuracies for the assessment of dignity and entity were evaluated. RESULTS: Mean sensitivity, specificity, positive and negative predictive value for detection of malignancy with DVP were 48.4% /67.8% /92.7% and 29.3%, respectively. Total diagnostic accuracies for dignity/entity were 63.9% /38.5% (HCC: 58.3% /25.8%; ICC: 73.3% /50%; FNH: 67.9% /67.9%). Interreader-agreement was moderate (κ= 0.42-0.58). Differential diagnosis between ICC and HCC was most challenging. CONCLUSION: Although developed to improve diagnostic accuracy and objectivity in the assessment of focal liver lesions, DVP alone seems insufficient for differential diagnosis of HCC, ICC and FNH and cannot replace the skills of an experienced observer.

[Influence of therapy on risk of cancer in rheumatoid arthritis. Pathophysiological principles]. / Einfluss der Therapie auf das Krebsrisiko bei rheumatoider Arthritis. Pathophysiologische Grundlagen.

The increased incidence of certain tumor entities in chronic inflammation and infections as well as the increased tumor risk under immunosuppression, illustrate the multiple and complex influences of the immune system on tumor pathogenesis. It is therefore conceivable that immunomodulatory therapy for rheumatoid arthritis (RA) could also influence the risk of malignancies, apart from treating the underlying disease. Basic scientific research studies have identified various signal transduction pathways that are relevant for tumorigenesis and tumor defense mechanisms. This review presents the current knowledge on the effects of the immune system on the occurrence of cancer and tries, where possible, to relate it to specific treatment options.

Early response to anti-tumoral treatment in hepatocellular carcinoma--can quantitative contrast-enhanced ultrasound predict outcome?

PURPOSE: In order to detect an early response to anti-angiogenic therapy, this study aims at analyzing specific effects of a sorafenib-based regime on intra-tumoral D-CEUS flow parameters of patients with HCC. MATERIALS AND METHODS: Videos of the arterial phase were captured before initiation of a therapy with sorafenib and 1 and 3 months after (n = 9). Patients receiving a non-anti-angiogenic therapy (TACE, n = 10) served as a comparison group. Cross-sectional imaging was performed at the same time points and patients were followed up for 1 year. RESULTS: In the responder group (RE), the absolute (percentage) TTP was 11.28 s ± 2.03 s (1.00) before treatment, 13.60 s ± 1.52 s (1.53 ± 0.08) after one month (p = 0.0405), and 16.17 s ± 2.35 s (1.46 ± 0.07) after three months of treatment (p = 0.0071). The TTP increased significantly in the RE group as early as 1 month after initiation of sorafenib compared to the non-responder group. There were no significant differences in the non-responder group or between the NR and the TACE group at any time point. D-CEUS values from all sorafenib-treated patients showed good accordance with RECICL (response evaluation criteria in cancer of the liver) criteria (R2 = 0.7154, p = 0.0001). CONCLUSIONS: Quantitative CEUS reveals variations of dynamic parameters of blood flow during anti-tumoral therapy in liver cancer patients. Further investigations and clinical trails have to confirm that the TTP is a promising parameter in the prediction of early response to sorafenib-based therapy.

Mesenteric transit time using contrast-enhanced ultrasound (CEUS) does not correlate with disease activity in Crohn's disease.

PURPOSE: Evaluation of mesenteric transit time (MTT) - measured by contrast-enhanced ultrasound - as a marker for inflammatory activity in Crohn's disease. MATERIALS AND METHODS: The time of maximum enhancement of the contrast agent in the superior mesenteric artery and vein was determined visually and by software analysis. The MTT was calculated as the difference between these two time points. Findings were correlated with the Harvey-Bradshaw Index (HBI) using the Pearson correlation coefficient (r). In addition, a healthy control group was evaluated both in the fasting state and 1, 2, 3 and 4 hours postprandially. RESULTS: In 20 healthy controls the mean visual MTT during fasting was 9.76 ± 2.83 sec and decreased to a minimum 1 hour after the meal (6.6 ± 2.27 sec). 45 patients with Crohn's disease (9 males, 36 females, mean age 35 years) had a mean HBI of 5.9 ± 4.7 points. The mean software-based MTT of 9.76 ± 3.7 sec was significantly higher (p = 0.034) than the mean visual MTT of 8.22 ± 3.05 sec. The two figures correlated well (r = 0.72, p < 0.001). The HBI correlated neither with the visual (r = 0.14, p = 0.371) nor with the software-based (r = 0.16, p = 0.293) MTT. CONCLUSION: The MTT decreases in the first two hours after eating. The visually assessed and the software-based MTT correlate well, however MTT does not correlate with disease activity in patients with Crohn's disease.