Hepatocellular carcinoma (HCC) occurs predominantly in patients with liver cirrhosis. Here, we show an innovative RNA-based targeted approach to enhance endogenous albumin production whilst reducing liver tumour burden. We designed short-activating RNAs (saRNA) to enhance expression of C/EBPα (CCAAT/enhancer-binding protein-α), a transcriptional regulator and activator of albumin gene expression. Increased levels of both C/EBPα and albumin mRNA in addition to a 3-fold increase in albumin secretion and 50% decrease in cell proliferation was observed in C/EBPα-saRNA transfected HepG2 cells. Intravenous injection of C/EBPα-saRNA in a cirrhotic rat model with multifocal liver tumours increased circulating serum albumin by over 30% showing evidence of improved liver function. Tumour burden decreased by 80% (p = 0.003) with a 40% reduction in a marker of pre-neoplastic transformation. Since C/EBPα has known anti-proliferative activities via retinoblastoma, p21 and cyclins; we used mRNA expression liver cancer specific microarray in C/EBPα-saRNA transfected HepG2 cells to confirm down-regulation of genes strongly enriched for negative regulation of apoptosis, angiogenesis and metastasis. Up-regulated genes were enriched for tumour suppressors and positive regulators of cell differentiation. A quantitative PCR and Western-blot analysis of C/EBPα-saRNA transfected cells suggested that in addition to the known anti-proliferative targets of C/EBPα, we also observed suppression of IL6R, c-Myc and reduced STAT3 phosphorylation. Conclusion We demonstrate for the first time that a novel injectable saRNA-oligonucleotide that enhances C/EBPα expression successfully reduces tumour burden and simultaneously improves liver function in a clinically relevant liver cirrhosis/HCC model.

Rationale and objectives : Despite all the benefits and effectiveness of the coronavirus disease 2019 (COVID-19) vaccines mentioned in recent clinical trials, some post-vaccination side effects such as lymphadenopathy (LAP) were observed. The present study reviewed all studies with imaging findings presentation of LAP after COVID-19 vaccination. Materials and methods : We conducted a literature search in online databases, including Scopus, Medline (PubMed), Web of Science, Embase (Elsevier), Cochrane library, and Google Scholar. Results : A total of 19 studies (68 cases), including 60 (88.2%) females and 8 (11.8%) males with a presentation of LAP after COVID-19 vaccination, were reviewed. LAP was identified after first or second dosages of three types of COVID-19 vaccines, including Pfizer-BioNTech (n = 30, 44.1%), Moderna (n = 17, 25%), and Oxford-AstraZeneca (n = 1, 1.5%). In 20 (29.4%) cases, vaccine type was not reported or only reported as mRNA COVID-19 vaccine. The median days of LAP presentation after the first and second dosages of COVID-19 vaccination, were 12 and 5 days, respectively. Most of the LAP imaging findings related to COVID-19 vaccination (n = 66, 97%) were seen from first day to four weeks after vaccination. However, LAP remained after 5 and 6 weeks of the first and second dosages of COVID-19 vaccination with decreased lymph nodes’ size and residual cortical thickening in two cases. Conclusion : This review study of cases with LAP-associated COVID-19 vaccination guides radiologists and physicians to rely on patient's clinical context and updated resources to prevent potential disease upstaging and change in therapy.

In this group of patients, it appears that this new approach is feasible and safe. Efficacy remains to be proven in future, randomized, prospective studies.

Introduction: Hepatic cancer is a highly lethal tumour with increasing worldwide incidence. These tumours are characterized by the proliferation of malignant cells, generalised immunosuppression and chronic inflammation marked with an increase in inflammatory markers as a neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR) and overexpression of CD4+CD39+ on T lymphocytes. The studies have outlined immunomodulatory changes in liver cancer patients as the plausible explanation for the better survival. The aim of this pilot study was understand the possible immunomodulatory effect of radiofrequency (RF) energy and liver resection (non-radiofrequency based devices; non-RF device) in relation to NLR, PLR and expression of CD4+CD39+ T lymphocytes and compare the magnitude of these changes.Material and Methods: In the present study, 17 patients with hepatic cancer were prospectively divided into treatment groups radiofrequency ablation (RFA group) and Liver resection using non-RF devices (LR group). A blood sample was collected from each patient, one month before and after the procedure and compared with the blood samples of age-matched healthy volunteers for group wise comparison. The Mann-Whitney U test, Mc Nemar test and Wilcoxon rank test were used for statistical comparisons as appropriate.Results: A decrease in NLR was reported after RFA from 4.7±3.3 to 3.8±1.8 (P=0.283), in contrary to an increase from 3.5±2.8 to 4.5±3.2 (P=0.183) in LR group. Likewise, a decrease was discerned in PLR following RFA from 140.5±79.5 to 137±69.2 respectively (P=0.386) and increase in the LR group from 116±42.2 to 120.8±29 respectively (P=0.391). A significant decrease in CD4+CD39+ lymphocytes from 55.8±13.8 to 24.6±21.1 (P=0.03) was observed in RFA group whilst a significant increase was reported in LR group from 47.6±8.8 to 55.7±33.2 (P=0.38).Conclusion: Studies have shown that decrease in the NLR, PLR and expression of CD4+CD39+ on T lymphocytes as the marker of better survival in hepatic cancer patients and our findings have confirmed that these changes can be induced following application of RF energy. Moreover, this could be the explanation of better survival observed in different studies using RFA or other RF-based devices in comparison to non-RF based liver resection techniques. However, further larger studies are needed to confirm these findings.

Background: Malignant biliary and/or pancreatic obstruction has often encountered in the advanced stages of periampullary and cholangicarcinomas. HabibTM Radiofrequency (RF) ablation has been successfully used in the management of various cancers of liver and pancreas. Percutaneous HPB probe (EMcision Ltd, London, UK) is a new addition to this class of tools. It is an endoluminal Radiofrequency (RF) catheter which works on the principle of ablation and induces coagulative necrosis to recanalize the obstructed duct. The aim of this study is to address the technical details of canalization, feasibilities and outcomes of percutaneous endo-luminal Radiofrequency (RF) catheter in patients with unresectable malignancy with obstructed bile and pancreatic duct (PD).Material and Method: A total of 134 patients with inoperable malignant obstruction of biliary and PD underwent RF based percutaneous endoluminal RF ablation in a tertiary referral centre between December 15th, 2010 to August 7th, 2015. This device was used in a sequential manner with an intent to recanalize the obstructed. Following the initial catheter drainage of the duct, subsequent percutaneous endobiliary RF ablation, the metallic stent was placed to recanalize the obstructed bile and PD secondary to unresectable malignancy under real-time fluoroscopic guidance.Results: The percutaneous RF based ablation of obstructed bile duct and PD with metallic stent placement was successfully achieved in 130 (97.01%) cases. The three failures were noted in cases of biliary obstruction whilst, one with PD obstruction. The patency restored in 124 and patients, where the procedure was successfully completed and revealed clinical improvement reported.Conclusion: The percutaneous endoluminal RF based ablation of obstructed duct with metallic stent placement appeared to be a safe, effective procedure and may improve survival in patients with advanced stage cancer presenting with biliary and PD obstruction. Considering the above mentioned evidence, this modality may stand ahead of stenting alone. This could be considered as viable modality in management of such patients where very limited treatment options are available.