-
1.
Long noncoding RNA FEZF1-AS1 in human cancers.
Zhou, Y, Xu, S, Xia, H, Gao, Z, Huang, R, Tang, E, Jiang, X
Clinica chimica acta; international journal of clinical chemistry. 2019;:20-26
Abstract
Long noncoding RNAs (lncRNAs) have been shown to play key roles in various human tumors. Ectopic expression of the lncRNA FEZ finger zinc 1 antisense 1 (FEZF1-AS1) have been reported in different cancers, including colorectal cancer, gastric neoplasia, hepatocellular carcinoma and so on. Summarizing all literature correlated with FEZF1-AS1, it is obvious that FEZF1-AS1 is mainly involved in tumorigenesis and progression through competing endogenous RNA (ceRNA) which sponges tumor-suppressive microRNA (miRNA) and recruiting mechanism. Moreover, the aberrant expression of FEZF1-AS1 is related to clinical features of patients with cancers, and regulates cellular proliferation, anti-apoptosis, invasion and metastasis through diverse underlying mechanisms. The role of FEZF1-AS1 in carcinogenesis and progression suggests that it may be a potential diagnostic biomarker or a novel therapeutic target for cancers.
-
2.
Lenvatinib: A Review in Hepatocellular Carcinoma.
Al-Salama, ZT, Syed, YY, Scott, LJ
Drugs. 2019;(6):665-674
Abstract
Lenvatinib (Lenvima®) is an oral small molecule inhibitor of multiple receptor tyrosine kinases, and is approved for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC) in the USA, EU, Japan and China. The approval of lenvatinib was based on results of the randomized, open-label, multinational, non-inferiority phase III REFLECT trial in patients with unresectable HCC, who had not received treatment for advanced disease. In REFLECT, lenvatinib was non-inferior, but not superior, to sorafenib (current standard of care) for overall survival (OS). However, lenvatinib was associated with significant improvements compared with sorafenib in terms of all secondary endpoints [higher objective response rate (ORR), and longer progression-free survival (PFS) and time to progression (TTP)]. Lenvatinib had a generally manageable tolerability profile in REFLECT, with the most common treatment-emergent adverse events being hypertension, diarrhoea, decreased appetite and decreased weight. Given its non-inferior efficacy to sorafenib and manageable tolerability profile, lenvatinib represents a long-awaited alternative option to sorafenib for the first-line systemic treatment of patients with unresectable HCC. Further clinical experience may be required to fully define the position of lenvatinib in this setting.
-
3.
Prevention of Hepatocellular Carcinoma by Statins: Clinical Evidence and Plausible Mechanisms.
Kim, G, Kang, ES
Seminars in liver disease. 2019;(2):141-152
Abstract
Statins, or 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are widely used to treat hypercholesterolemia for primary and secondary prevention of cardiovascular disease. Statins inhibit HMG-CoA reductase, the rate-limiting step in cholesterol synthesis, and modulate the downstream signaling of the mevalonate pathway. In addition to the primary effect, the antitumor effect of statins can be associated with mevalonate pathway-mediated and nonmevalonate pathway-mediated mechanisms, which improve endothelial function and lead to proapoptotic, antiproliferative, antiinflammatory, and antifibrotic properties. Statins are implicated in the improvement of metabolic status. Statins are orally available and safely and widely used for long-term treatment; they represent a novel approach for the prevention and treatment for hepatocellular carcinoma (HCC). Although several observational studies and experimental studies have revealed the preventive and therapeutic potential of statins for HCC treatment, further prospective interventional studies and randomized control trials are warranted to confirm these observations.
-
4.
90Y-Loaded Microsphere SIRT of HCC Patients With Portal Vein Thrombosis: High Clinical Impact of 99mTc-MAA SPECT/CT-Based Dosimetry.
Garin, E, Rolland, Y, Edeline, J
Seminars in nuclear medicine. 2019;(3):218-226
Abstract
Radioembolization with 90Y-loaded microspheres based on classical prescription methods is increasingly applied to hepatocellular carcinoma (HCC) patients with portal vein thrombosis (PVT). In recent years, pretherapeutic predictive dosimetry based on technetium-99m macroaggregated albumin (MAA) quantitative scintigraphy using SPECT/CT has been developed. This paper presents an overview on the MAA-based dosimetry concept, discusses important confounding factors, such segmentation methods, and specific angiographic considerations required for a simulation-based dosimetric evaluation. The concept of "dosimetric angiography" is then introduced for the first time. Main results available are reported as a threshold tumor dose, allowing a response, between 100 and 120 Gy with 90Y-loaded resin microspheres and between 205 and 257 Gy with 90Y-loaded glass microspheres. Impact of MAA-based dosimetry and MAA PVT targeting on overall survival is also reported. Due to those dosimetric advances, personalized dosimetric approaches based on MAA dosimetry are now available, with specific endpoints, for both 90Y-loaded resin or glass microsphere. The clinical impact of personalized dosimetry in PVT patients is particularly high, as a median overall survival of 20.2 months has been reported for good PVT candidate treated with glass microspheres (tumor-absorbed dose ≥205 Gy and good PVT targeting) as against only 3 months for poor candidate (tumor-absorbed dose <205 Gy or poor PVT targeting), and as a significant amount of patients where downstaged and resected (12%) in the same study.
-
5.
The role of vitamin D in hepatic metastases from colorectal cancer.
Shaw, E, Massaro, N, Brockton, NT
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2018;(3):259-273
Abstract
Colorectal cancer (CRC) represents a significant health burden worldwide, comprising approximately 10% of annual cancer cases globally. Hepatic metastases are the most common site of CRC metastasis, and are the leading cause of death in CRC patients. There is strong epidemiologic evidence for an inverse association between vitamin D status and risk of CRC; however, the role of vitamin D in the natural history of liver metastases has not yet been investigated. Several researchers have proposed hallmarks of metastases; crucially, metastases can be blocked by interrupting just one rate-limiting step. Vitamin D status has been implicated in each proposed hallmark of metastasis. The aim of this review is to examine the potential role for vitamin D in reducing the development of hepatic metastases from CRC and outline the candidate mechanisms by which vitamin D may mediate these effects. The results of ongoing randomised intervention trials are eagerly awaited to determine whether addressing vitamin D insufficiency in CRC patients could reduce the occurrence of liver metastases, and the consequent morbidity and mortality.
-
6.
Evidence Supporting LI-RADS Major Features for CT- and MR Imaging-based Diagnosis of Hepatocellular Carcinoma: A Systematic Review.
Tang, A, Bashir, MR, Corwin, MT, Cruite, I, Dietrich, CF, Do, RKG, Ehman, EC, Fowler, KJ, Hussain, HK, Jha, RC, et al
Radiology. 2018;(1):29-48
-
-
Free full text
-
Abstract
The Liver Imaging Reporting and Data System (LI-RADS) standardizes the interpretation, reporting, and data collection for imaging examinations in patients at risk for hepatocellular carcinoma (HCC). It assigns category codes reflecting relative probability of HCC to imaging-detected liver observations based on major and ancillary imaging features. LI-RADS also includes imaging features suggesting malignancy other than HCC. Supported and endorsed by the American College of Radiology (ACR), the system has been developed by a committee of radiologists, hepatologists, pathologists, surgeons, lexicon experts, and ACR staff, with input from the American Association for the Study of Liver Diseases and the Organ Procurement Transplantation Network/United Network for Organ Sharing. Development of LI-RADS has been based on literature review, expert opinion, rounds of testing and iteration, and feedback from users. This article summarizes and assesses the quality of evidence supporting each LI-RADS major feature for diagnosis of HCC, as well as of the LI-RADS imaging features suggesting malignancy other than HCC. Based on the evidence, recommendations are provided for or against their continued inclusion in LI-RADS. © RSNA, 2017 Online supplemental material is available for this article.
-
7.
Contrast enhanced ultrasound for focal liver lesions: how accurate is it?
Barr, RG
Abdominal radiology (New York). 2018;(5):1128-1133
Abstract
With the recent FDA approval for characterization of focal liver lesions (FLL) in both pediatric and adult patients using Lumason (sulfur hexafluoride microbubbles), increased use of ultrasound contrast for routine clinical use is expected. This agent has been available for many years in Europe and Asia, and a large body of literature is available regarding the sensitivity and specificity of this agent. In addition, a few studies have directly compared CEUS to CECT and CEMRI for the characterization of focal liver lesions. This paper reviews the literature to provide a background to investigators in the United States as to the accuracy of CEUS in the characterization of FLL. This paper reviews the literature regarding sulfur hexafluoride microbubbles (Lumason in the USA and Sonovue in the rest of the world) since it is the only FDA approved agent in the USA for characterization of FLL. The results of other ultrasound contrast agents which are not FDA approved for abdominal indications (approval for cardiac indications) most likely will have similar results.
-
8.
Effectiveness and safety of robotic-assisted versus laparoscopic hepatectomy for liver neoplasms: A meta-analysis of retrospective studies.
Hu, L, Yao, L, Li, X, Jin, P, Yang, K, Guo, T
Asian journal of surgery. 2018;(5):401-416
Abstract
This meta-analysis aimed to investigate the effectiveness and safety of RAH and LLR for liver neoplasms. A systematic search was performed in PubMed, EMbase, the Cochrane Library, Web of science, and China Biology Medicine disc up to July 2016 for studies that provided comparisons between the surgical outcomes of RAH and LLR for liver neoplasms. WMD, OR and 95% CI were calculated and data combined using the random-effect model. The quality of the evidence was assessed using GRADE methods. A total of 17 studies were included in the meta-analysis, in which 487 patients were in the RAH group and 902 patients were in the LLR group. The meta-analysis results indicated: compared to LLR, RAH was associated with more estimated blood loss, longer operative time, and longer time to first nutritional intake (p < 0.05). There was no significant difference in length of hospital stay, conversion rate during operation, R0 resection rate, complications and mortality (p > 0.05). Three studies reported the total cost, and the result showed a higher cost in the RAH group when compared with the LLR group (p < 0.05). This meta-analysis indicated that RAH and LLR display similar effectiveness and safety in hepatectomy. Considering the lack of high quality original studies, prospective clinical trials should be conducted to provide strong evidence for clinical guidelines formation, and the insurance coverage policies should be established to promote the application of robotic surgery in the future.
-
9.
Regorafenib: A Review in Hepatocellular Carcinoma.
Heo, YA, Syed, YY
Drugs. 2018;(9):951-958
Abstract
Regorafenib (Stivarga®), a small molecule inhibitor of multiple kinases, is the first drug to be approved for the treatment of hepatocellular carcinoma (HCC) in patients who have progressed during or after sorafenib therapy. Its approval was based on the results of the randomized, double-blind, placebo-controlled, multinational, phase III RESORCE trial in patients with HCC who had progressed during sorafenib therapy. In RESORCE, regorafenib significantly prolonged overall survival (OS; primary endpoint), progression-free survival (PFS) and time to progression (TTP) compared with placebo, with the OS benefit appearing to be largely due to disease stabilization. Regorafenib had an acceptable tolerability profile. The most common treatment-related adverse events in the regorafenib group included hand-foot skin reaction, fatigue, diarrhoea and hypertension. No fatal hepatic failure was reported with regorafenib in patients with HCC in RESORCE. In conclusion, current evidence suggests that regorafenib is an important new targeted therapy option for the treatment of HCC patients who have progressed on sorafenib therapy.
-
10.
Hepatocarcinoma: genetic and epigenetic features.
Lombardi, A, Grimaldi, A, Zappavigna, S, Misso, G, Caraglia, M
Minerva gastroenterologica e dietologica. 2018;(1):14-27
Abstract
HCC is the third leading cause of cancer-related deaths worldwide, accounting for about 1 million deaths annually. The incidence of HCC is highest in Asia and Africa, where the endemic high prevalence of hepatitis B and hepatitis C strongly predisposes to the development of chronic liver disease and subsequent development of HCC. Patients with HCC generally present at an advanced stage due to compensated cirrhosis defined by the absence of pathognomonic symptoms, resulting in death within 6 to 20 months, suggesting an urgent need in treatment modalities that will dramatically decrease the mortality rate of HCC. The molecular hepatocarcinogenesis is, however, a gradual process during which genetic alterations progressively accumulate and lead to HCC through intermediate preneoplastic stages. With the advent of whole genome sequencing tools, various mutations associated with HCC have been identified, which have advanced our molecular understanding of HCC. However, the frequency of these mutations is rare, and these genetic mutations only partly explain the etiology of the disease. Better understanding and characterization of novel genetic and epigenetic alterations, which are important to hepatocarcinogenesis, may help understand the molecular pathogenesis of HCC, as well as providing novel therapeutic targets for HCC treatment. Further consideration should be given to developing more effective molecular diagnostic markers and targeted drug therapy.