Percutaneous Image-Guided Pancreatic Duct Drainage: Technique, Results and Expected Benefits.

PURPOSE: The aim of this study is to provide a technical detail and feasibility of percutaneous image-guided pancreatic duct (PD) drainage and to discuss its subtleties in a series of patients with obstructed PD. MATERIALS AND METHODS: Thirty patients presenting with PD obstruction from pancreatic head tumour or pancreatitis were subjected to percutaneous image-guided PD drainage under a guidance of ultrasound or computed tomography. Following the successful puncture of PD, a locking loop drainage catheter was placed using conventional guidewire techniques under real-time fluoroscopy guidance. RESULTS: The percutaneous drainage of obstructed PD was completed in 29 (96.7%) patients as an independent therapeutic intent or as a bridge to further percutaneous procedures. Clinical improvement following drainage was documented by the gradual reduction in clinical symptoms, including pain, nausea and fever and improved blood test results, showing the significant decrease of amylase concentration. The amount of pancreatic fluid drained post procedure was between 300 and 900 mL/day. No major procedure-related complications were observed. Subsequently, 14 of 29 patients underwent further procedures, including endoluminal placement of metal stent with or without radiofrequency ablation, balloon assisted percutaneous descending litholapaxy (BAPDL), endoluminal biopsy and balloon dilatation using the same drainage tract. CONCLUSION: The percutaneous PD drainage appears to be a safe and effective procedure. It should be considered in patients with obstructed PD secondary to malignancy, pancreatitis etc., where endoscopic retrograde cannulation has been failed or impracticable. The procedure can also be contemplated either as an independent treatment option or as an initial step for the subsequent therapeutic endoluminal procedures

Immunomodulatory changes following isolated RF ablation in colorectal liver metastases: a case report

Background: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths in developed countries. The liver is the most prevalent site of metastasis from CRC. Currently, the gold-standard treatment for colorectal liver metastases (CLMs) is surgical resection. However, depending on the pattern of the disease, a significant number of patients may require different approaches alone or in combination with surgery, including thermal ablation (radiofrequency (RFA) or microwave (MWA) ablation) or transarterial liver-directed therapies, although the latter is not yet part of the standard treatment for CRC liver metastases. Methods and Results: We present the case of a 63-yearold man with bilobar CLM who was treated with transarterial embolization (TAE) and RFA followed by chemotherapy. A post-RFA study of immune parameters revealed the downregulation of CD39 expression in the circulating CD4+ T cell population and a reduction of the serum levels of cytokines IL-10, TGF-β, IFN-gamma and IL-17, which positively correlated with the diminished serum level of gamma-glutamyl transferase (GGT) and the subdued inflammatory markers: the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR). Later, the patient underwent chemotherapy. Liver failure developed within two years and nine months following tumour ablation, leading to the death of the patient. Conclusions: However, the denial of adjuvant chemotherapy by the patient gave us the opportunity to assess the immunomodulatory changes following RFA in the absence of any other therapeutic modalities

Study to evaluate the immunomodulatory effects of radiofrequency ablation compared to surgical resection for liver cancer

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

A novel RNA oligonucleotide improves liver function and inhibits liver carcinogenesis in vivo

Hepatocellular carcinoma (HCC) occurs predominantly in patients with liver cirrhosis. Here we show an innovative RNA-based targeted approach to enhance endogenous albumin production while reducing liver tumor 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 tumors increased circulating serum albumin by over 30%, showing evidence of improved liver function. Tumor burden decreased by 80% (P = 0.003) with a 40% reduction in a marker of preneoplastic transformation. Since C/EBPα has known antiproliferative activities by way of retinoblastoma, p21, and cyclins, we used messenger RNA (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 tumor suppressors and positive regulators of cell differentiation. A quantitative polymerase chain reaction (PCR) and western blot analysis of C/EBPα-saRNA-transfected cells suggested that in addition to the known antiproliferative targets of C/EBPα, we also observed suppression of interleukin (IL)6R, c-Myc, and reduced STAT3 phosphorylation.CONCLUSION: A novel injectable saRNA-oligonucleotide that enhances C/EBPα expression successfully reduces tumor burden and simultaneously improves liver function in a clinically relevant liver cirrhosis/HCC model

Novel RNA oligonucleotide improves liver function and inhibits liver carcinogenesis in vivo

UnlabelledHepatocellular carcinoma (HCC) occurs predominantly in patients with liver cirrhosis. Here we show an innovative RNA-based targeted approach to enhance endogenous albumin production while reducing liver tumor 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 tumors increased circulating serum albumin by over 30%, showing evidence of improved liver function. Tumor burden decreased by 80% (P = 0.003) with a 40% reduction in a marker of preneoplastic transformation. Since C/EBPα has known antiproliferative activities by way of retinoblastoma, p21, and cyclins, we used messenger RNA (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 tumor suppressors and positive regulators of cell differentiation. A quantitative polymerase chain reaction (PCR) and western blot analysis of C/EBPα-saRNA-transfected cells suggested that in addition to the known antiproliferative targets of C/EBPα, we also observed suppression of interleukin (IL)6R, c-Myc, and reduced STAT3 phosphorylation.ConclusionA novel injectable saRNA-oligonucleotide that enhances C/EBPα expression successfully reduces tumor burden and simultaneously improves liver function in a clinically relevant liver cirrhosis/HCC model