Hepatic Malignancies Research Articles

Microwave Ablation of Hepatocellular Carcinoma and Liver Metastases: Challenges, Opportunities, and Future Directions

AbstractChronic liver disease predisposes patients to the development of hepatocellular carcinoma (HCC), and the degree of liver dysfunction helps dictate the management of patients with primary hepatic malignancy. Percutaneous ablation is an increasingly utilized treatment modality for patients with hepatocellular carcinoma who are poor surgical candidates, particularly when treatment goals include sparing hepatic parenchyma in the setting of hepatic dysfunction. Various thermal and non-thermal ablation modalities have historically been used to treat HCC. With advances in ablation technology, modern microwave (MW) ablation systems have become increasingly utilized in HCC as well as hepatic metastatic disease management due to larger and more predictable ablation zones. The evolution of ablation technology has resulted in the growth of ablation as a safe and effective treatment option for patients with primary and secondary liver tumors.

CT-guided microwave ablation of hepatic malignancies via transpulmonary approach without ancillary techniques.

Objectives:The objectives of the study were to determine the safety and efficacy of computed tomography (CT)-guided transpulmonary percutaneous microwave ablation (MWA) for hepatic malignancies without the use of ancillary techniques.Material and Methods:A retrospective review was performed on patients who underwent MWA for hepatic malignancy between January 2014 and February 2020 at a single tertiary center. Imaging was reviewed for each procedure to identify MWA showing transpleural transgression on CT scans. For these patients, demographics, ablation data, pulmonary complication rate, and predictors of pneumothorax were analyzed.Results:A total of 71 consecutive sessions (62.1 ± 11.3 years, 79% of males) of MWA were performed to treat 71 tumors (1.90 ± 0.96 cm) via transpulmonary approach under CT guidance. Technical success was achieved in all cases immediately after the procedure. At 1-month follow-up, 65/69 (94.2%) patients had no residual disease (two patients were lost to follow-up). Pulmonary complications occurred in 26/71 (36.6%) sessions, and 15/26 (57.7%) were minor requiring no intervention. Pneumothorax occurred in 14/71 (19.7%) sessions, and the rate of major pneumothorax requiring chest tube was 8/71 (11.3%). Lesions on the left side of the liver (segments I–IV) and intraprocedural probe adjustment were found to be independent predictors of developing major pneumothorax (P = 0.007 and 0.028, respectively). There were no reported pulmonary complications at the 1-month follow-up.Conclusion:CT-guided transpulmonary MWA is safe and effective in treating hepatic malignancies. Although it is associated with the risk of developing pulmonary complications, patients underwent successful ablation of their hepatic malignancies without life-threatening complications and mortality.

Aurantio-Obtusin Attenuates Non-Alcoholic Fatty Liver Disease Through AMPK-Mediated Autophagy and Fatty Acid Oxidation Pathways.

Nonalcoholic fatty liver disease (NAFLD), manifested as the aberrant accumulation of lipids in hepatocytes and inflammation, has become an important cause of advanced liver diseases and hepatic malignancies worldwide. However, no effective therapy has been approved yet. Aurantio-obtusin (AO) is a main bioactive compound isolated from Cassia semen that has been identified with multiple pharmacological activities, including improving adiposity and insulin resistance. However, the ameliorating effects of AO on diet-induced NAFLD and underlying mechanisms remained poorly elucidated. Our results demonstrated that AO significantly alleviated high-fat diet and glucose-fructose water (HFSW)-induced hepatic steatosis in mice and oleic acid and palmitic acid (OAPA)-induced lipid accumulation in hepatocytes. Remarkably, AO was found to distinctly promote autophagy flux and influence the degradation of lipid droplets by inducing AMPK phosphorylation. Additionally, the induction of AMPK triggered TFEB activation and promoted fatty acid oxidation (FAO) by activating PPARα and ACOX1 and decreasing the expression of genes involved in lipid biosynthesis. Meanwhile, the lipid-lowing effect of AO was significantly prevented by the pretreatment with inhibitors of autophagy, PPARα or ACOX1, respectively. Collectively, our study suggests that AO ameliorates hepatic steatosis via AMPK/autophagy- and AMPK/TFEB-mediated suppression of lipid accumulation, which opens new opportunities for pharmacological treatment of NAFLD and associated complications.

Diagnosis and Follow-up of Incidental Liver Lesions in Children.

Incidental liver lesions are identified in children without underlying liver disease or increased risk of hepatic malignancy in childhood. Clinical and imaging evaluation of incidental liver lesions can be complex and may require a multidisciplinary approach. This review aims to summarize the diagnostic process and follow-up of incidental liver lesions based on review of the literature, use of state-of-the-art imaging, and our institutional experience. Age at presentation, gender, alpha fetoprotein levels, tumor size, and imaging characteristics should all be taken into consideration to optimize diagnosis process. Some lesions, such as simple liver cyst, infantile hemangioma, focal nodular hyperplasia (FNH), and focal fatty lesions, have specific imaging characteristics. Recently, contrast-enhanced ultrasound (CEUS) was Food and Drug Administration (FDA)-approved for the evaluation of pediatric liver lesions. CEUS is most specific in lesions smaller than 3 cm and is most useful in the diagnosis of infantile hemangioma, FNH, and focal fatty lesions. The use of hepatobiliary contrast in MRI increases specificity in the diagnosis of FNH. Recently, lesion characteristics in MRI were found to correlate with subtypes of hepatocellular adenomas and associated risk for hemorrhage and malignant transformation. Biopsy should be considered when there are no specific imaging characteristics of a benign lesion. Surveillance with imaging and alpha fetoprotein (AFP) should be performed to confirm the stability of lesions when the diagnosis cannot be determined, and whenever biopsy is not feasible.

Identification of Immune-Related Prognostic mRNA and lncRNA in Patients with Hepatocellular Carcinoma.

Background As the most common hepatic malignancy, hepatocellular carcinoma (HCC) has a high incidence; therefore, in this paper, the immune-related genes were sought as biomarkers in liver cancer. Methods In this study, a differential expression analysis of lncRNA and mRNA in The Cancer Genome Atlas (TCGA) dataset between the HCC group and the normal control group was performed. Enrichment analysis was used to screen immune-related differentially expressed genes. Cox regression analysis and survival analysis were used to determine prognostic genes of HCC, whose expression was detected by molecular experiments. Finally, important immune cells were identified by immune cell infiltration and detected by flow cytometry. Results Compared with the normal group, 1613 differentially expressed mRNAs (DEmRs) and 1237 differentially expressed lncRNAs (DElncRs) were found in HCC. Among them, 143 immune-related DEmRs and 39 immune-related DElncRs were screened out. These genes were mainly related to MAPK cascade, PI3K-AKT signaling pathway, and TGF-beta. Through Cox regression analysis and survival analysis, MMP9, SPP1, HAGLR, LINC02202, and RP11-598F7.3 were finally determined as the potential diagnostic biomarkers for HCC. The gene expression was verified by RT-qPCR and western blot. In addition, CD4 + memory resting T cells and CD8 + T cells were identified as protective factors for overall survival of HCC, and they were found highly expressed in HCC through flow cytometry. Conclusion The study explored the dysregulation mechanism and potential biomarkers of immune-related genes and further identified the influence of immune cells on the prognosis of HCC, providing a theoretical basis for the prognosis prediction and immunotherapy in HCC patients.

The potential role of FNDC5/irisin in various liver diseases: awakening the sleeping beauties.

Fibronectin type III domain-containing protein 5 (FNDC5) is a transmembrane protein and the precursor of irisin, which serves as a systemic exerkine/myokine with multiple origins. Since its discovery in 2012, this hormone-like polypeptide has rapidly evolved to a component significantly involved in a gamut of metabolic dysregulations and various liver diseases. After a decade of extensive investigation on FNDC5/irisin, we are still surrounded by lots of open questions regarding its diagnostic and therapeutic values. In this review, we first concentrated on the structure-function relationship of FNDC5/irisin. Next, we comprehensively summarised the current knowledge and research findings regarding pathogenic roles/therapeutic applications of FNDC5/irisin in the context of non-alcoholic fatty liver disease, fibrosis, liver injury due to multiple detrimental insults, hepatic malignancy and intrahepatic cholestasis of pregnancy. Moreover, the prominent molecules involved in the underlying mechanisms and signalling pathways were highlighted. As a result, emerging evidence reveals FNDC5/irisin may act as a proxy for diagnosing liver disease pathology, a sensitive biomarker for assessing damage severity, a predisposing factor for surveilling illness progression and a treatment option with protective/preventive impact, all of which are highly dependent on disease grading and contextually pathological features.

WDR4 gene polymorphisms increase hepatoblastoma susceptibility in girls.

Hepatoblastoma, originating from hepatoblasts, is the most common hepatic malignancy. WD repeat domain 4 (WDR4) is a subunit of RNA N(7)-methylguanine (m7G) methyltransferase complex. Recently, WDR4 has shown oncogenic potential in various adult cancers, but its roles in pediatric cancers have not been reported. We performed a case-control study (313 cases vs. 1446 controls) to investigate whether genetic variants in the WDR4 gene influence hepatoblastoma susceptibility in the Chinese Han nationality. We first determine the genotypes of five WDR4 gene polymorphisms (rs2156315 C>T, rs2156316 C>G, rs6586250 C>T, rs15736 G>A, rs2248490 C>G) in participants, using the Taqman assay. And then, an unconditional logistic regression analysis was performed to assess the association between WDR4 gene polymorphisms and hepatoblastoma risk. Overall, we did not find any polymorphism significantly associated with the risk of developing hepatoblastoma. Instead, the stratified analysis revealed that the co-existence of 2-5 risk genotypes increased hepatoblastoma risk by 2.23 folds in girls (adjusted odds ratio=2.23, 95% confidence interval=1.17-4.23, P=0.014). In conclusion, our results demonstrate that single selected polymorphisms were too weak to exert a significant effect on the whole study population. However, in combination, two or more WDR4 gene polymorphisms significantly conferred increased hepatoblastoma risk in girls. Our findings may encourage more genetic association studies to discover significant polymorphisms in the WDR4 gene for hepatoblastoma.

Open Hepatic Resection: Outcomes Audit from a Low Volume Tertiary Care Centre in Pakistan

Introduction: We are a tertiary care institution in a developing country where open surgery is the only option for hepatic resection due to low volumes and inadequate infrastructure. We conducted an audit of open hepatic resection at our hospital to review the short-term outcomes. Methods: This was a retrospective review of 175 patients who underwent hepatic resection at Aga Khan University Hospital, Pakistan, from January 2008 to December 2020. The outcomes studies included in-hospital morbidity, 30-day & 90-day mortality. A univariate analysis was done to identify risk factors associated with morbidity and mortality. Results: The mean age of the patients was 53±14 years including 99(56.6%) males. Nearly half (53.7%) of the patients had at least one comorbid condition. Indication for surgery included primary hepatic malignancy in 104 (59.4%), metastatic malignancies in 39 (22.3%) & benign liver pathology in 32 (18.3%) patients. Major hepatic resections were performed in 64 (36.6%) patients. The mean estimated blood loss was 658±547ml and the duration of surgery was 278±121 minutes. Postoperative complications were observed in 59 (33.7%) patients and mortality rates at 30-day and 90-day were 5 (3%) and 7 (4%) respectively. The presence of comorbid conditions (p=0.025) especially DM (p=0.006), longer duration of surgery (p=0.009) & need for transfusion (p=0.016) had a significant association with postoperative morbidity. Conclusion: Despite low volumes, short-term outcomes of open hepatic resection at our center are comparable to international standards. Preoperative optimization of comorbid conditions and assessing the need for transfusion are crucial to improve the overall morbidity.

“Awake Surgery” for Liver Resection

Background: Minimally invasive liver resection has become in recent years a standard of care for hepatic malignancies. Considering the necessity to treat even more frail patients, sometimes general anesthesia is avoided in consideration of respiratory complications and surgical treatment is abandoned in favor of less invasive approach, impacting the possibility to achieve a curative treatment. Epidural anesthesia has shown to reduce such respiratory complications, especially in old patients with pre-existing pulmonary disease.

Detection and Frequency of TP53 and -Catenin Somatic Diver Mutations by Droplet Digital PCR Using Cell Free DNA of Hepatitis B Virus Induced Hepatocellular Carcinoma Patients

Background and Aims: Hepatocellular carcinoma(HCC) is the most common primary hepatic malignancy accounting for 0.7 million fatalities per year. Hepatitis B virus (HBV) infection is a commonest cause of HCC. HCC is diagnosed mostly at an advance stage for which development of test is required for early detection. Detection of somatic driver mutations with increased frequency can be an attractive strategy and the present study was undertaken for this. Earlier studies found that the somatic driver mutation accounts HCC in 56% all cases.

Atypical Manifestation of Primary Hepatocellular Carcinoma and Hepatic Malignancy Mimicking Lesions.

Hepatocellular carcinoma (HCC) can be diagnosed noninvasively on multiphasic CT and MRI based on its distinctive imaging findings. These features include arterial phase hyperenhancement and washout on portal or delayed phase images. However, radiologists face significant diagnostic challenges because some HCCs exhibit atypical imaging characteristics. In addition to many HCC-mimicking lesions, such as arterioportal shunts, combined HCC-cholangiocarcinoma, intrahepatic cholangiocarcinoma, and hemangioma present a challenge for radiologists in actual clinical practice. The ability to distinguish HCCs from mimickers on initial imaging examinations is crucial for appropriate management and treatment decisions. Therefore, this pictorial review presents the imaging findings of atypical HCCs and HCCs mimicking malignant and benign lesions and discusses important clues that may help narrow down the differential diagnosis.

Diagnostic and Prognostic Value of miRNAs in Hepatoblastoma: A Systematic Review With Meta-Analysis.

Background and aim: Increasing evidence has revealed the valuable diagnostic and prognostic applications of dysregulated microRNAs (miRNAs) in hepatoblastoma (HB), the most common hepatic malignancy during childhood. However, these results are inconsistent and remain to be elucidated. In the present study, we aimed to systematically compile up-to-date information regarding the clinical value of miRNAs in HB. Methods: Articles concerning the diagnostic and prognostic value of single miRNAs for HB were searched from databases. The sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and hazard ratios (HRs) were separately pooled to explore the diagnostic and prognostic performance of miRNA. Subgroup and meta-regression analyses were further carried out only in the event of heterogeneity. Results: In all, 20 studies, involving 264 HB patients and 206 healthy individuals, met the inclusion criteria in the 6 included literature articles. For the diagnostic analysis of miRNAs in HB, the pooled SEN and SPE were 0.76 (95% CI: 0.72-0.80) and 0.75 (95% CI: 0.70-0.80), respectively. Moreover, the pooled PLR was 2.79 (95% CI: 2.12-3.66), NLR was 0.34 (95% CI: 0.26-0.45), DOR was 10.24 (95% CI: 6.55-16.00), and AUC was 0.83, indicating that miRNAs had moderate diagnostic value in HB. For the prognostic analysis of miRNAs in HB, the abnormal expressions of miR-21, miR-34a, miR-34b, miR-34c, miR-492, miR-193, miR-222, and miR-224 in patients were confirmed to be associated with a worse prognosis. The pooled HR was 1.74 (95% CI: 1.20-2.29) for overall survival and 1.74 (95% CI: 1.31-2.18) for event-free survival, suggesting its potential as a prognostic indicator for HB. Conclusion: To the best of our knowledge, this is the first comprehensive systematic review and meta-analysis that examines the diagnostic and prognostic role of dysregulated miRNAs in HB patients. The combined meta-analysis results supported the previous individual finds that miRNAs might provide a new, noninvasive method for the diagnostic and prognostic analyses of HB.

Primary Hepatic Leiomyosarcoma: Case Report and Literature Review

Introduction: Primary hepatic leiomyosarcoma (PHL) is an extremely rare tumor, accounting for 0.2–2% of all primary hepatic malignancies, with less than 70 cases reported worldwide. Herein, we report a case of a 48-year-old female patient with a large surgically resected PHL.

Yttrium-90 Hepatic Therapy and the Increasing Role of Volumetric Voxel-based Post Therapy Dosimetry: A Case Report

Yttrium-90 (Y-90) therapy has become an important component to the care of patients with primary hepatic malignancies and lesions that have metastasized to the liver. Therapy is administered through an intra-arterial procedure after an interventional procedure is performed using an albumin labeled product to ensure therapy will be delivered to the target volume of interest with minimal migration from the target of choice. In the past, dose to target has been measured by activity delivered and qualitative deposition of dose on metabolic imaging post application. Imaging tools such as single positron emission computer tomography (SPECT) and digital positron emission tomography have given us insight into quantitative dose to volumetric tumor target and dose to normal tissue. Recent validation of computational software has provided voxel-based dosimetry similar to applied processes established in radiation oncology planning systems. This development presents an opportunity to create dose volume analysis similar to teletherapy and brachytherapy dose delivery for Y-90 therapy. In this case report, we review Y-90 dosimetry on a patient with dual diagnosis of a locally advanced high-risk adenocarcinoma of the prostate which required treatment to the para-aortic lymph nodes located in the same axial plane with renal parenchyma. Although not clinically anticipated, hepatocellular carcinoma was serendipitously discovered at the time of staging for prostate cancer. Treatment dosimetry of the hepatocellular carcinoma is reviewed in retrospect with voxel-based commercial software. Same day SPECT study suggested dose localized to the liver, however voxel planning software confirmed unintentional dose to additional structures including the right kidney and uninvolved liver which influenced radiation therapy treatment planning for prostate carcinoma. With modern available tools, post therapy dosimetry for Y-90 can be performed in a manner similar to volumetric dosimetry used in radiation oncology and provide valuable dose volume analysis of dose delivered to target and additional tissue.

METTL14 gene polymorphisms influence hepatoblastoma predisposition in Chinese children: Evidences from a seven-center case-control study.

Hepatoblastoma as the most prevalent hepatic malignancy in children, its etiology remains unclear. N6-Methyladenosine (m6A) modification which can modify various physiological processes, plays a critical role in tumorigenesis. Methyltransferase-like 14 (METTL14), an important component of the m6A methyltransferase complex, remains elusive during hepatoblastoma occurrence and development. We explored the relationship between METTL14 gene polymorphisms (rs1064034 T>A, rs298982 G>A, rs62328061 A>G, rs9884978 G>A, and rs4834698 T>C) and hepatoblastoma susceptibility from 313 patients and 1446 controls. The role of METTL14 polymorphisms in hepatoblastoma was evaluated by odds ratios (ORs) and 95% confidence intervals (CIs). Of the included subjects, 308 patients and 1444 controls were successfully genotyped. We did not find any significant correlation between the risk of hepatoblastoma and the five potentially functional METTL14 polymorphisms individually. However, the presence of 4-5 risk genotypes exhibited a significant increased hepatoblastoma risk (adjusted OR=1.32, 95% CI=1.03-1.69, P=0.031) compared to those carriers with 0-3 risk genotypes. Furthermore, the stratified analysis demonstrated that the rs1064034 AA genotype, rs62328061 AG/GG genotypes, rs4834698 TC/CC genotypes, and 4-5 risk genotypes were related to hepatoblastoma susceptibility in certain subgroups. The expression quantitative trait loci (eQTL) analysis revealed that rs1064034 T>A and rs4834698 T>C were correlated with the expression levels of METTL14 and its surrounding genes. Prospectively, these findings suggested that METTL14 polymorphisms may correlation with hepatoblastoma susceptibility and provide a fresh insight into the genetic underpinnings of m6A modification in hepatoblastoma.

Periprocedural factors associated with overall patient survival following percutaneous image-guided liver tumor cryoablation

Purpose To assess the impact of periprocedural factors, including adverse events, on overall patient survival following image-guided liver tumor cryoablation procedures. Methods In this retrospective single-institution study, 143 patients (73 male, 70 female, ages 29–88) underwent 169 image-guided liver tumor cryoablation procedures between October 1998 and August 2014. Patient, tumor and procedural variables were recorded. The primary outcome was overall survival post-procedure (Kaplan–Meier analysis). Secondary outcomes were the impact of 15 variables on patient survival, which were assessed with multivariate cox regression and log-rank tests. Results Mean tumor diameter was 2.5 ± 1.2 cm. 26 of 143 (18.2%) patients had primary hepatic malignancies; 117 of 143 (81.8%) had liver metastases. Survival analysis revealed survivor functions at 3, 5, 7, 10 and 12 years post-ablation of 0.54, 0.37, 0.30, 0.17 and 0.06, with mean survival time of 40.8 ± 4.9 months. Tumor size ≥4 cm (p = .018), pre-procedural platelet count <100 × 103/μL (p = .023), and prior local radiation therapy (p = .014) were associated with worse overall patient survival. Grade 3 or higher adverse events were not associated with reduced survival (p = .49). Conclusions All variables associated with overall survival were patient-related and none were associated with the cryoablation procedure. Pre-procedural thrombocytopenia, larger tumor size and history of prior local radiation therapy were independent risk factors for reduced overall survival in patients undergoing hepatic cryoablation. Adverse events related to hepatic cryoablation were not associated with decreased survival.

Long non-coding RNA titin-antisense RNA1 contributes to growth and metastasis of cholangiocarcinoma by suppressing microRNA-513a-5p to upregulate stratifin

ABSTRACT Cholangiocarcinoma (CCA) is one of the most common histological types of primary hepatic malignancy and is associated with poor overall prognosis, causing a ponderous burden on human life. Hence, it is necessary to elucidate the pathogenesis of CCA. The objective of our research was to shed light on the mechanism through which long non-coding RNA titin-antisense RNA1 (lncRNA TTN-AS1) is involved in the development of CCA. Reverse transcription quantitative polymerase chain reaction was used to detect TTN-AS1 expression in CCA samples and cells. Functional experiments were performed using the Cell Counting Kit-8, 5-ethynyl-2ʹ-deoxyuridine, transwell, and in vivo tumor growth assays. The relationship between TTN-AS1, miR-513a-5p, and stratifin (SFN) was explored using a dual luciferase reporter assay, RNA immunoprecipitation (RIP) experiment, and Pearson correlation analysis. The result showed that TTN-AS1 and SFN are highly expressed in CCA tissues. Bioinformatics analysis, luciferase reporter and RIP experiments revealed the correlation between TTN-AS1, miR-513a-5p, and SFN. In addition, silencing TTN-AS1 mitigated CCA cell proliferation and migration. Mechanistically, miR-513a-5p is sponged by TTN-AS1. The miR-513a-5p inhibitor abolished the effect of TTN-AS1 silencing on the aggressive behaviors of CCA cells. Furthermore, we showed that miR-513a-5p is a regulator of CCA by targeting SFN. TTN-AS1 induced CCA cell growth and metastasis via the miR-513a-5p/SFN pathway, which offers a new strategy for therapeutic interventions for CCA.

Rare Malignant Indications for Liver Transplantation: A Collaborative Transplant Study Report.

Introduction: Hepatocellular carcinoma (HCC) is by far the leading malignant indication for liver transplantation (LT). Few other malignancies, including cholangiocellular carcinoma (CCC), metastases from neuroendocrine tumors (NET), and sarcomas of the liver (LSAR), also are commonly accepted indications for LT. However, there is limited information on their outcome after LT.Methods: Graft and patient survival in 14,623 LTs performed in patients with hepatocellular carcinoma, CCC, NET, and LSAR from 1988 to 2017 and reported to the Collaborative Transplant Study were analyzed.Results: The study group consisted of 13,862 patients who had HCC (94.8%), 498 (3.4%) who had CCC, 100 (0.7%) who had NET, and 163 (1.1%) who had LSAR. CCC patients showed a 5-year graft survival rate of 32.1%, strikingly lower than the 63.2% rate in HCC, 51.6% rate in NET, and 64.5% rate in LSAR patients (P < 0.001 for all vs. CCC). Multivariable Cox regression analysis revealed a significantly higher risk of graft loss and death due to cancer during the first five post-transplant years in CCC vs. HCC patients (HR 1.77 and 2.56; P < 0.001 for both). The same risks were increased also in NET and LSAR patients but did not reach statistical significance.Conclusion: Among patients with rare malignant indications for LT, CCC patients showed significantly impaired graft as well as patient survival compared to HCC patients. The observed differences might challenge traditional decision-making processes for LT indication and palliative treatment in specific hepatic malignancies.

The Current Status and Research Progress of Antiviral Therapy in HCV-Associated Lymphoma --Review

Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease. HCV is not only related to hepatic malignancies but may also promote lymphoid neoplasms. Currently, research has confirmed HCV-related lymphoma, including marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma (LPL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma (BL). Many types of research have shown that antiviral therapy can improve or even remission several HCV-related lymphomas. The direct-acting antiviral agents (DAAs) (such as NS5A protease inhibitors, NS4/4A protease inhibitors and viral polymerase inhibitors) have shown clinical advantages of high efficacy and low side effects for both virus elimination and tumor regression in several HCV-related lymphomas, which may make the selected HCV-related lymphoma patients treated without chemotherapy. In this review the research progress and development direction of antiviral therapy in treating HCV-related lymphoma has summarized briefly.

Theragnostics in primary and secondary liver tumors: the need for a personalized approach.

Primary and secondary hepatic tumors have a dramatic impact in oncology. Despite many advances in diagnosis and therapy, the management of hepatic malignancies is still challenging, ranging from various loco-regional approaches to system therapies. In this scenario, theragnostic approaches, based on the administration of a radiopharmaceuticals' pair, the first labeled with a radionuclide suitable for the diagnostic phase and the second one bound to radionuclide emitting particles for therapy, is gaining more and more importance. Selective internal radiation therapy (SIRT) with microspheres labeled with 90Y or 166Ho is widely used as a loco-regional treatment for primary and secondary hepatic tumors. While 166Ho presents both gamma and beta emission and can be therefore considered a real "theragnostic" agent, for 90Y-microspheres theragnostic approach is realized at the diagnostic phase through the utilization of macroaggregates of human albumin, labeled with 99mTc as "biosimilar" agent respect to microspheres. The aim of the present review was to cover theragnostic applications of 90Y/166Ho-labeled microspheres in clinical practice. Furthermore, we report the preliminary data concerning the potential role of some emerging theragnostic biomarkers for hepatocellular carcinoma, such as glypican-3 (GPC3) and prostate specific membrane antigen (PSMA).