Platelets and hepatocellular cancer: Bridging the bench to the clinics

Growing interest is recently being focused on the role played by the platelets in favoring hepatocellular cancer (HCC) growth and dissemination. The present review reports in detail both the experimental and clinical evidence published on this topic. Several growth factors and angiogenic molecules specifically secreted by platelets are directly connected with tumor progression and neo-angiogenesis. Among them, we can list the platelet-derived growth factor, the vascular endothelial growth factor, the endothelial growth factor, and serotonin. Platelets are also involved in tumor spread, favoring endothelium permeabilization and tumor cells\u2019 extravasation and survival in the bloodstream. From the bench to the clinics, all of these aspects were also investigated in clinical series, showing an evident correlation between platelet count and size of HCC, tumor biological behavior, metastatic spread, and overall survival rates. Moreover, a better understanding of the mechanisms involved in the platelet\u2013tumor axis represents a paramount aspect for optimizing both current tumor treatment and development of new therapeutic strategies against HCC

Management of adverse events with tailored sorafenib dosing prolongs survival of hepatocellular carcinoma patients

Background & Aims: Sorafenib is associated with multiple adverse events (AEs), potentially causing its permanent interruption. It is unknown how physicians\u2019 experience has impacted on the management of these AEs and consequently on clinical outcomes. We aimed to assess whether AE management changed over time and if these modifications impacted on treatment duration and overall survival (OS). Methods: We analysed the prospectively collected data of 338 consecutive patients who started sorafenib between January 2008 and December 2017 in 3 tertiary care centres in Italy. Patients were divided according to the starting date: Group A (2008\u20132012; n = 154), and Group B (2013\u20132017, n = 184). Baseline and follow-up data were compared. In the OS analysis, patients who received second-line treatments were censored when starting the new therapy. Results: Baseline characteristics, AEs, and radiological response were consistent across groups. Patients in Group B received a lower median daily dose (425 vs. 568 mg/day, p <0.001) due to more frequent dose modifications. However, treatment duration was longer (5.8 vs. 4.1 months, p = 0.021) with a trend toward a higher cumulative dose in Group B. Notably, the OS was also higher (12.0 vs. 11.0 months, p = 0.003) with a sharp increase in the 2-year survival rate (28.1 vs. 18.4%, p = 0.003) in Group B. Multivariate time-dependent Cox regression analysis confirmed later period of treatment (2013\u20132017) as an independent predictor of survival (HR 0.728; 95% CI 0.581\u20130.937; p = 0.013). Unconsidered confounders were unlikely to affect these results at the sensitivity analysis. Conclusions: Experience in the management of sorafenib-related AEs prolongs treatment duration and survival. This factor should be considered in the design of future randomised clinical trials including a sorafenib treatment arm, as an underestimate of sample size may derive. Lay summary: Sorafenib has been the standard frontline systemic treatment for hepatocellular carcinoma for over a decade. Its tolerability is limited by different adverse events, which might lead to its permanent discontinuation in a sizeable proportion of patients. After a careful analysis of potential confounders, we demonstrated that the physicians\u2019 experience in managing adverse events related to sorafenib has improved over time, with longer treatment periods and less permanent discontinuation for toxicities. More importantly, these improvements also translated into longer patient survival. Our results have relevant repercussions in clinical practice and in the design of future clinical trials

Real-time contrast-enhanced ultrasound--a new simple tool for detection of peritoneal-pleural communications in hepatic hydrothorax.

PURPOSE: Hepatic hydrothorax is defined as the accumulation of pleural effusion in a cirrhotic patient in the absence of pulmonary or cardiac disease. Peritoneal fluid can pass into the pleural space through diaphragmatic fenestrations. The demonstration of such passage is important to establish the diagnosis of hepatic hydrothorax and can be achieved by intraperitoneal injection of nuclear contrast agents. Our aim was to evaluate the ability of contrast enhanced ultrasound in the detection of peritoneal-pleural communications. MATERIALS AND METHODS: Seven patients with cirrhotic ascites and pleural effusion were studied in order to make a diagnosis of hepatic hydrothorax. SonoVue was injected into the peritoneal cavity (9.8 mL), and the peritoneal and pleural cavities were monitored by ultrasound. All patients were then studied using a nuclear scan. RESULTS: Passage of SonoVue from the peritoneal to the pleural cavities was seen in 5 patients. In 2 patients, no passage of contrast agent was detectable. Nuclear scan was consistent with contrast enhanced ultrasound in all patients. CONCLUSION: This study shows that the presence of peritoneal-pleural communications can be demonstrated by real time contrast enhanced ultrasound, whose results are comparable to those of nuclear scan. Contrast enhanced ultrasound is cheaper and could theoretically be performed wherever ultrasound facilities are available

CD133+ hematopoietic stem cells reinfusion in end-stage liver disease (ESLD): final results of a phase I clinical trial

none13nononeC. Margini, L. Brodosi, S. Lorenzini, L. Catani, V. Giudice, R. Giordano, A. Casadei, D. Sollazzo, F.G. Foschi, M. Baccarani, M. Bernardi, R. Lemoli, P. AndreoneC. Margini, L. Brodosi, S. Lorenzini, L. Catani, V. Giudice, R. Giordano, A. Casadei, D. Sollazzo, F.G. Foschi, M. Baccarani, M. Bernardi, R. Lemoli, P. Andreon