The aberrant expression of miR-221 is a hallmark of human cancers, including hepatocellular carcinoma (HCC), and its involvement in drug resistance, together with a proved
efficacy of anti-miR-221 ...molecules, strengthen its role as an attractive target candidate in the oncologic field. The discovery of biomarkers predicting the response to treatments represents a clinical challenge in the personalized treatment era. This study aimed to investigate the possible role of miR-221 as a circulating biomarker in HCC patients undergoing sorafenib treatment as well as to evaluate its contribution to sorafenib resistance in advanced HCC.
A chemically induced HCC rat model and a xenograft mouse model, together with HCC-derived cell lines were employed to analyze miR-221 modulation by Sorafenib treatment. Data from the functional analysis were validated in tissue samples from surgically resected HCCs. The variation of circulating miR-221 levels in relation to Sorafenib treatment were assayed in the animal models and in two independent cohorts of patients with advanced HCC.
MiR-221 over-expression was associated with Sorafenib resistance in two HCC animal models and caspase-3 was identified as its target gene, driving miR-221 anti-apoptotic activity following Sorafenib administration. Lower pre-treatment miR-221 serum levels were found in patients subsequently experiencing response to Sorafenib and an increase of circulating miR-221 at the two months assessment was observed in responder patients.
MiR-221 might represent a candidate biomarker of likelihood of response to Sorafenib in HCC patients to be tested in future studies. Caspase-3 modulation by miR-221 participates to Sorafenib resistance.
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Abstract This review illustrates the state of the art clinical applications and the future perspectives of ultrasound elastographic methods for the evaluation of chronic liver diseases, including the ...most widely used and validated technique, transient elastography, followed by shear wave elastography and strain imaging elastography. Liver ultrasound elastography allows the non-invasive evaluation of liver stiffness, providing information regarding the stage of fibrosis, comparable to liver biopsy which is still considered the gold standard; in this way, it can help physicians in managing patients, including the decision as to when to start antiviral treatment. The characterization of focal liver lesions and the prognostic role of the elastographic technique in the prediction of complications of cirrhosis are still under investigation.
Contrast-enhanced ultrasonography (CEUS), providing relevant informations not available with non-enhanced ultrasonography, greatly impacted the practice of liver imaging. The characterization of ...focal liver lesions (FLLs), is obtained in a rapid, accurate and safe way and is considered the main hepatic indication; however CEUS offers other established or emergent relevant applications. Metastases detection and assessment of response to locoregional tumor treatment are accepted applications with specific indications. Needle guidance in case of poorly or non visible target lesions at conventional ultrasound is also accepted. The early assessment of response to systemic treatment, and in particular to antiangiogenic ones, by quantification software is an emergent application. The manageability of CEUS determined also its use in the operating theatre, improving the accuracy of intraoperatory US with a significant impact on final surgical strategy. In cirrhotic patients, the role of CEUS was proven highly accurate and sensitive in the characterization of portal vein thrombosis, by identification of contrast arterial enhancement inside the thrombus, that occurs only in case of neoplastic origin. In recent years microbubbles taken up by Kupffer cells, thus possessing a "postvascular" phase, were registered as ultrasound contrast agent in Japan (Sonazoid). During the post-vascular phase tumoral tissue tend to appear as a contrast defect image due to the lack of Kupffer cells, strongly contributing to tumor staging beside characterization. Newly developed techniques, such as fusion imaging or real-time three dimensional US, in addition to other applications of CEUS, in terms of post-transplantation or cholecystitis-related complications, have been recently proposed and will be discussed.
During the first outbreak of Coronavirus disease 2019 (COVID-19) Emergency Departments (EDs) were overcrowded. Hence, the need for a rapid and simple tool to support clinical decisions, such as the ...ROX index (Respiratory rate – OXygenation), defined as the ratio of peripheral oxygen saturation and fraction of inspired oxygen, to respiratory rate. The aim of the study was to evaluate the accuracy of the ROX index in predicting hospitalization and mortality in patients with a diagnosis of COVID-19 in the ED. The secondary outcomes were to assess the number of readmissions and the variations in the ROX index between the first and the second admission. This was an observational prospective monocentric study, carried out in the ED of Sant’Orsola-Malpighi Hospital in Bologna, Italy. Five hundred and fifty-four consecutive patients with COVID-19 were enrolled and the ROX index was calculated. Patients were followed until hospital discharge or death. A ROX index value < 25.7 was associated with hospitalization (area under the curve AUC = 0.737, 95% CI 0.696–0.779,
p
< 0.001). The ROX index < 22.3 was statistically related to higher 30-day mortality (AUC = 0.764, 95% CI 0.708–0.820,
p
< 0.001). Eight patients were discharged and returned to the ED within the subsequent 7 days, their mean ROX index was 30.3 (6.2; range 21.9–39.4) at the first assessment and 24.6 (5.5; 14.5–29.5) at the second assessment, (
p
= 0.012). The ROX index, together with laboratory, imaging and clinical findings, correlated with the need for hospital admission, mechanical ventilation and mortality risk in COVID-19 patients.
Introduction and aim: As first receivers of suspected coronavirus disease 2019 (COVID-19) patients, clinicians of the Emergency Department (ED) have to rapidly perform the first clinical assessment ...evaluating the intensity of care needed. So far, clear management guidelines still lack. We identified variables associated with hospitalization in order to give a quick tool to assist clinicians in stratifying cases based on the severity at their arrival at the ED and in predicting the need for hospital care. Methods: This is a monocentric observational prospective study enrolling COVID-19 patients. A score for hospitalization prediction (CovHos Score) was created using variables associated with hospitalization at multivariate analysis and then validated on an internal subsequent cohort. Results: A total of 667 patients were included; 465 (69.7%) were hospitalized and 108 (16.2%) died at 30-days follow-up. In a multivariate analysis, male sex, age>65, alveolar-to-arterial oxygen gradient percentage increase compared to that expected for age, neutrophils/lymphocytes ratio and C-reactive protein levels were significantly associated with a higher rate of hospital admission. A CovHos score cut-off of 12 points predicted hospitalization with 85% sensitivity and 82.4 % specificity (area under a receiver operating characteristic curve AUROC = 0.909, 95% CI 0.884 - 0.935). Similar results were obtained in the validation court. A cut-off of 22 has 79% sensitivity and 77% specificity in predicting mortality (AUROC = 0.824; 95% CI 0.782-0.866); sensitivity and specificity were respectively 71.4% and 71.3% in the validation group. Conclusions: Although medical judgment still remains crucial, the CovHos score is an effective tool to assist emergency clinicians in predicting the need for hospitalization or to optimize allocation in a shortage of hospital resources.
Abstract Aim We tested the relationship between hepatic haemodynamics assessed by Doppler ultrasonography and liver stiffness assessed by Transient Elastography in hepatitis C related chronic liver ...disease. Methods Three liver Doppler ultrasound parameters (hepatic artery resistance index, splenic artery resistance index and waveform pattern in hepatic veins) and liver stiffness measured by Transient Elastography were analysed in one hundred consecutive patients affected by hepatitis C related chronic liver disease. Results Hepatic and splenic arteries resistance indexes correlate significantly ( p < 0.0001 for both) with liver stiffness. A hepatic artery resistance index cut-off value of 0.64 provided sensitivity and specificity respectively of 84.4% and 69.1% for predicting liver stiffness ≤or >13 kPa, whereas a splenic artery resistance index cut-off value of 0.56 provided sensitivity and specificity respectively of 81.3% and 48.5%. The coincidental finding of both resistance indexes above the respective cut-off values showed a good accuracy in identifying patients with liver stiffness values >13 kPa (accuracy = 78%, +LR = 2.90, −LR = 0.31). A significant difference in liver stiffness values was evident between patients with triphasic and bi- or monophasic waveform pattern ( p = 0.005). Conclusions Hepatic and splenic arteries resistance indexes and the hepatic veins waveform pattern assessed by Doppler ultrasound may provide information similar to that of Transient Elastography in hepatitis C related chronic liver disease.
Since its introduction in clinical practice, ultrasound technology has greatly impacted patient management, particularly in the case of liver diseases, where hepatologists usually perform ultrasound ...examinations. Clinicians are increasingly aware of the great potential of ultrasound waves and of the recent innovations that exploit the mechanical properties of ultrasound waves. Thus, at present, not only B-mode ultrasound but also contrast-enhanced ultrasound and, more recently, elastosonography are used worldwide in various settings. This review aims to describe why clinicians should be aware of ultrasound-based techniques, how they should use these techniques for assessing focal liver lesions, and how these techniques impact patient management. We will review the clinical potential of ultrasound-related techniques, starting from lesion detection, moving to characterization, and concluding with their utility in guiding treatments and analyzing their effects.
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•The LR-5 CEUS class is an optimal diagnostic tool for HCC.•The other LR classes (LR-3, LR-4 and LR-M) require histological confirmation.•These data could change the diagnostic ...algorithm of HCC.
The use of contrast enhanced ultrasound (CEUS) for the diagnosis of hepatocellular carcinoma (HCC) in cirrhosis was questioned because of the risk of a false positive diagnosis in cases of cholangiocarcinoma. The American College of Radiology has recently released a scheme (CEUS Liver Imaging Reporting and Data System LI-RADS®) to classify lesions at risk of HCC investigated by CEUS. The aim of the present study was to validate this LI-RADS scheme for the diagnosis of HCC.
A total of 1,006 nodules from 848 patients with chronic liver disease at risk of HCC were collected in five Italian centers and retrospectively analyzed. Nodules were classified as LR-5, (HCC) if ≥1 cm with arterial phase hyperenhancement, and late washout (onset ≥60 s after contrast injection) of mild degree. Rim enhancement and/or early and/or marked washout qualified lesions as LR-M (malignant, but not specific for HCC). Other combinations qualified lesions at intermediate risk for HCC (LR-3) or probable HCC (LR-4). Diagnostic reference standard was CT/MRI diagnosis of HCC (n = 506) or histology (n = 500).
The median nodule size was 2 cm. Of 1,006 nodules, 820 (81%) were HCC, 40 (4%) were cholangiocarcinoma, 116 (11%) regenerative nodules (±dysplastic). The LR-5 category (52% of all nodules) was 98.5% predictive of HCC, with no risk of misdiagnosis for pure cholangiocarcinoma. Sensitivity for HCC was 62%. All LR-M nodules were malignant and the majority of non-hepatocellular origin. Over 75% of cholangiocarcinomas were LR-M. The LR-3 category included 203 lesions (HCC 96 47%) and the LR-4 202 (HCC 173 87%).
The CEUS LI-RADS class LR-5 is highly specific for HCC, enabling its use for a confident non-invasive diagnosis.
This is a retrospective study of approximately 1,000 focal lesions at risk for hepatocellular carcinoma (HCC). Herein, we demonstrate that the refined definition of the typical contrast enhanced ultrasound pattern of HCC introduced by the Liver Imaging Reporting and Data System (LI-RADS®) practically abolishes the risk of misdiagnosis of other malignant entities (e.g. cholangiocarcinoma) for HCC with negligible reduction in sensitivity. These data support the use of contrast enhanced ultrasound to diagnose HCC in cirrhosis.
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