Immunotherapy has remarkably revolutionized the management of advanced HCC and prompted clinical trials, with therapeutic agents being used to selectively target immune cells rather than cancer ...cells. Currently, there is great interest in the possibility of combining locoregional treatments with immunotherapy for HCC, as this combination is emerging as an effective and synergistic tool for enhancing immunity. On the one hand, immunotherapy could amplify and prolong the antitumoral immune response of locoregional treatments, improving patients' outcomes and reducing recurrence rates. On the other hand, locoregional therapies have been shown to positively alter the tumor immune microenvironment and could therefore enhance the efficacy of immunotherapy. Despite the encouraging results, many unanswered questions still remain, including which immunotherapy and locoregional treatment can guarantee the best survival and clinical outcomes; the most effective timing and sequence to obtain the most effective therapeutic response; and which biological and/or genetic biomarkers can be used to identify patients likely to benefit from this combined approach. Based on the current reported evidence and ongoing trials, the present review summarizes the current application of immunotherapy in combination with locoregional therapies for the treatment of HCC, and provides a critical evaluation of the current status and future directions.
Regorafenib is a diphenylurea oral multikinase inhibitor, structurally comparable to sorafenib, which targets a variety of kinases implicated in angiogenic and tumor growth-promoting pathways. ...Regorafenib was the first agent to positively show significant survival advantage as a second-line therapy in patients with unresectable hepatocellular carcinoma (HCC) who had previously failed first-line treatment with sorafenib. Recent evidence has shown that its antitumor efficacy is due to a comprehensive spectrum of tumor neo-angiogenesis and proliferation inhibition and immunomodulatory effects on the tumor microenvironment, which plays a crucial role in tumor development. This review addresses the rationale and supporting evidence for regorafenib’s efficacy in HCC that led to regorafenib’s approval as a second-line therapy. In addition, we review proof from clinical practice studies that validate the RESORCE trial results. We discuss regorafenib’s potential role in the newly emerging therapeutic strategy based on combination with immune checkpoint blockade and its possible extensibility to patient categories not enrolled in the registrative study.
The increased detection of pancreatic cysts in recent years has triggered extensive diagnostic investigations to clarify their potential risk of malignancy, resulting in a large number of patients ...undergoing numerous imaging follow-up studies for many years. Therefore, there is a growing need for optimization of the current surveillance protocol to reduce both healthcare costs and waiting lists, while still maintaining appropriate sensibility and specificity. Imaging is an essential tool for evaluating patients with intraductal papillary mucinous neoplasms (IPMNs) since it can assess several predictors for malignancy and thus guide further management recommendations. Although contrast-enhanced magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) has been widely recommended by most international guidelines, recent results support the use of unenhanced abbreviated-MRI (A-MRI) protocols as a surveillance tool in patients with IPMN. In fact, A-MRI has shown high diagnostic performance in malignant detection, with high sensitivity and specificity as well as excellent interobserver agreement. The aim of this paper is, therefore, to discuss the current available evidence on whether the implementation of an abbreviated-MRI (A-MRI) protocol for cystic pancreatic lesion surveillance could improve healthcare economics and reduce waiting lists in clinical practice without significantly reducing diagnostic accuracy.
Changes in body composition are associated with poor outcomes in cancer patients including hepatocellular carcinoma (HCC). Sarcopenia, defined as the loss of skeletal muscle mass, quality and ...function, has been associated with a higher rate of complications and recurrences in patients with cirrhosis and HCC. The assessment of patient general status before HCC treatment, including the presence of sarcopenia, is a key-point for achieving therapy tolerability and to avoid short- and long-term complications leading to poor patients’ survival. Thus, we aimed to review the current literature evaluating the role of sarcopenia assessment related to HCC treatments and to critically provide the clinicians with the most recent and valuable evidence. As a result, sarcopenia can be predictive of poor outcomes in patients undergoing liver resection, transplantation and systemic therapies, offering the chance to clinicians to improve the muscular status of these patients, especially those with high-grade sarcopenia at high risk of mortality. Further studies are needed to clarify the predictive value of sarcopenia in other HCC treatment settings and to evaluate its role as an additional staging tool for identifying the most appropriate treatment. Besides, interventional studies aiming at increasing the skeletal muscle mass for reducing complications and increasing the survival in patients with HCC are needed.
Gastric cancer (GC) represents the fifth most frequently diagnosed cancer worldwide, with a poor prognosis in patients with advanced disease despite many improvements in systemic treatments in the ...last decade. In fact, GC has shown resistance to several treatment options, and thus, notable efforts have been focused on the research and identification of novel therapeutic targets in this setting. The tumor microenvironment (TME) has emerged as a potential therapeutic target in several malignancies including GC, due to its pivotal role in cancer progression and drug resistance. Therefore, several agents and therapeutic strategies targeting the TME are currently under assessment in both preclinical and clinical studies. The present study provides an overview of available evidence of the inflammatory TME in GC, highlighting different types of tumor-associated cells and implications for future therapeutic strategies.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and one of the most common causes of death among patients with cirrhosis, developing in 1–8% of them every ...year, regardless of their cirrhotic stage. The radiological features of HCC are almost always sufficient for reaching the diagnosis; thus, histological confirmation is rarely needed. However, the study of cirrhotic livers remains a challenge for radiologists due to the developing of fibrous and regenerative tissue that cause the distortion of normal liver parenchyma, changing the typical appearances of benign lesions and pseudolesions, which therefore may be misinterpreted as malignancies. In addition, a correct distinction between pseudolesions and malignancy is crucial to allow appropriate targeted therapy and avoid treatment delays.
The present review encompasses technical pitfalls and describes focal benign lesions and pseudolesions that may be misinterpreted as HCC in cirrhotic livers, providing the imaging features of regenerative nodules, large regenerative nodules, siderotic nodules, hepatic hemangiomas (including rapidly filling and sclerosed hemangiomas), segmental hyperplasia, arterioportal shunts, focal confluent fibrosis and focal fatty changes. Lastly, the present review explores the most promising new imaging techniques that are emerging and that could help radiologists differentiate benign lesions and pseudolesions from overt HCC.
INTRODUCTION:
A noninvasive diagnosis of clinically significant portal hypertension (CSPH) has important prognostic and therapeutic implications for patients with compensated advanced chronic liver ...disease. We aimed to validate and improve the available algorithms for the CSPH diagnosis by evaluating spleen stiffness measurement (SSM) in patients with compensated advanced chronic liver disease.
METHODS:
This is a retrospective study including patients with liver stiffness measurement (LSM) ≥10 kPa, no previous decompensation, and available measurements of hepatic venous pressure gradient, LSM, and SSM by transient elastography referring to our center in Bologna. The diagnostic algorithms were adequate if negative and positive predictive values were >90% when ruling out and ruling in CSPH, respectively; these models were validated in a cohort from Verona. The 5-year decompensation rate was reported.
RESULTS:
One hundred fourteen patients were included in the derivation cohort. The Baveno VII diagnostic algorithm (LSM ≤15 kPa + platelet count ≥150 × 10
9
/L to rule out CSPH and LSM >25 kPa to rule in CSPH) was validated; however, 40%–60% of the patients remained in the gray zone. The addition of SSM (40 kPa) to the model significantly reduced the gray zone to 7%–15%, maintaining adequate negative and positive predictive values. The diagnostic algorithms were validated in a cohort of 81 patients from Verona. All first decompensation events occurred in the “rule-in” zone of the model including SSM.
DISCUSSION:
The addition of SSM significantly improves the clinical applicability of the algorithm based on LSM and platelet count for CSPH diagnosis. Our models can be used to noninvasively identify candidates for nonselective beta-blocker treatment and patients at a high risk of decompensation.
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most people infected with the virus experience mild to ...moderate respiratory illness. However, some might become seriously ill and may develop acute respiratory distress syndrome (ARDS), thus requiring non-invasive or invasive mechanical ventilation. Furthermore, COVID-19 disease can involve also other organs and systems, causing several extra-pulmonary manifestations and, thus, negatively influencing the patient’s outcome. Imaging studies play a pivotal role in the monitoring of severely ill patients, especially those admitted to the intensive care unit (ICU), who can develop several potentially life-threatening complications, both from the infection itself and the mechanical supporting system. This widespread utility of imaging modalities calls for a deeper understanding of potential radiologic findings in this disease and the need for multidisciplinary collaboration between radiologists and anesthesiologists to provide actionable guidance to appropriate interventions under such conditions.
Objective
To prospectively assess the additional value of the hepatobiliary (HB) phase of Gd-EOB-DTPA-MRI in identifying and characterising small (≤2 cm) hepatocellular carcinomas (HCCs) undetermined ...in dynamic phases alone because of their atypical features, according to the AASLD criteria.
Methods
127 cirrhotic patients were evaluated with Gd-EOB-DTPA-MRI in two sets: unenhanced and dynamic phases; unenhanced, dynamic and HB phases. Sixty-two out of 215 nodules (29%) were atypical in 42 patients (33%).
Results
62 atypical nodules were reported at histology: high-grade dysplastic nodules (HGDN)/early HCC (
n
= 20), low-grade DN (LGDN) (
n
= 21), regenerative nodules (
n
= 17) and nodular regenerative hyperplasia (
n
= 4). The sensitivity, specificity, accuracy, positive and negative predictive value (PPV, NPV) were increased by the addition of the HB phase: 88.4–99.4%, 88–95%, 88–98.5%, 97–99%, and 65–97.5%, respectively. Twenty atypical nodules were malignant (32%), 19 of which were characterised only during the HB phase.
Conclusions
The HB phase is 11% more sensitive in the classification of HGDN/early HCC than dynamic MRI, with an added value of 32.5% in the NPV. The high incidence (33%) of atypical nodules and their frequent malignancy (32%) suggest the widespread employment of Gd-EOB-DTPA-MRI in the follow-up of small nodules (≤2 cm) in cirrhosis.
To evaluate the potential variability of Manganese (Mn
) in commercial pineapple juice (PJ) produced in different years and to identify the optimal Mn
concentration in the correct amount of PJ to be ...administered prior to Magnetic Resonance Cholangiopancreatography (MRCP) in order to suppress the gastroduodenal (GD) liquid signal. The Mn
concentration in PJ produced in different years was defined using Atomic Absorption Spectrometry. The optimal Mn
concentration and the amount of PJ, were estimated in an in-vitro analysis, and were then prospectively tested in a population of patients who underwent MRCP. The results were compared with those achieved with the previous standard amount of PJ used in a similar population. The concentrations of Mn
in commercial PJ produced in different years did not differ. A total amount of 150 ml (one glass) of PJ having a high Mn
content (2.37 mg/dl) was sufficient for the suppression of the GD liquid signal, despite the additional dilution caused by GD liquids since it led to a final concentration of Mn
of 0.5-1.00 mg/dl. The optimized single-dose oral administration of 150 ml (approximately one glass) of PJ having a high Mn
concentration prior to MRCP was adequate to guarantee the correct amount of Mn
to suppress the GD signal.
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