Pancreatic ductal adenocarcinoma (PDAC) is the third most common tumor of the gastrointestinal tract. At the time of diagnosis, the majority of PDACs shows already metastasis and does not qualify for curative surgery. Therefore, palliative chemotherapy has a very high priority, but recommendations after failure of first-line chemotherapies are quite limited. The aim of our analysis was to evaluate the efficacy of different second-line treatments after pretreatment with gemcitabine (57.5%), gemcitabine + erlotinib (25%), and platinum-based chemotherapy (17.5%). We included all patients with advanced PDAC treated with second-line chemotherapy in our department between 2005 and 2012. A total of 22 patients were treated with XELOX, 8 patients with FOLFOX, 6 patients with gemcitabine (+/- erlotinib) and 4 patients with FOLFIRI. On average, the patients received 4.2 cycles (standard deviation [SD] SD: 3.5) over a period of 2.5 months (SD: 2.6). The median overall survival (OS) for all patients was 5.4 months, progression-free survival was 3.5 months, and a tumor control was achieved in 21% of all cases. Toxicity profile was acceptable between the second-line chemotherapies and there was no significant difference in the other investigated end points. Interestingly, there was also no effect of the first-line treatment and their duration for the OS of the second-line therapy. According to our findings, second-line chemotherapies in advanced PDAC are beneficial and should be offered to patients, but we did not detect any superiority of a specific drug combination. More prospective, randomized and larger studies are necessary to evaluate new strategies for second-line chemotherapies.
Background and aimsLiver diseases are frequent causes of morbidity and mortality worldwide. Liver diseases can lead to cirrhosis, with the risk of acute-on-chronic liver failure (ACLF). For the detection of changes in hepatic hemodynamics, Doppler ultrasonography is a well-established method. We investigated hepatic hemodynamics via serial Doppler ultrasonography to determine the predictive value of changes in hepatic perfusion for the outcome in patients with severe liver diseases compared to established prognostic models such as the MELD (Model for End-Stage Liver Disease) or CLIF-C (Chronic Liver Failure-Consortium) ACLF score.MethodsIn this prospective cohort study, hepatic perfusion was quantified at baseline before the initiation of treatment and every third day by means of serial measurements of the hepatic artery resistance index (HARI) and the maximum portal vein velocity (PVv) using Doppler ultrasonography in 50 consecutive patients with severe liver diseases admitted to a medical intensive care unit (MICU). The recorded hemodynamic parameters were compared to the MELD score, and the CLIF-C ACLF score to analyze their utility for the prediction of the outcome of patients with severe liver diseases, liver cirrhosis, and ACLF.ResultsThe changes (delta) obtained by serial measurements of the MELD score, HARI, and PVv were analyzed through scatter plots. Bivariate correlation analysis yielded a new positive linear correlation between the delta-HARI and the delta-MELD score (r = 0.469; p < 0.001). In addition, our data revealed a new negative linear correlation between delta-PVv and the delta-MELD score (r = −0.279, p = 0.001). The leading cause of MICU mortality was acute-on-chronic liver failure (ACLF). A subgroup analysis of patients with liver cirrhosis revealed a positive linear correlation between the delta-HARI and the delta-CLIF-C-ACLF score (r = 0.252, p = 0.005). Of clinical relevance, non-survivors of ACLF exhibited a significantly higher mean value for the delta-HARI (0.010 vs. −0.005; p = 0.015) and a lower mean value for the delta-PVv (−0.7 vs. 1.9 cm/s; p = 0.037) in comparison to survivors of ACLF.ConclusionThis study shows the prognostic value of the assessment of hepatic perfusion in critical care patients with severe liver diseases by bedside Doppler ultrasound examination and its utility as an accurate predictor of the outcome in patients with ACLF. Increasing HARI and a decreasing PVv are predictors of an adverse outcome. Delta-HARI and delta-PVv are new biomarkers of prognosis and ACLF-related mortality in patients with liver diseases. Delta-HARI and delta-PVv may be helpful in guiding clinical decision-making, especially in catecholamine and fluid management.
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