Irreversible Electroporation For Hepatocellular Carcinoma: Longer-Term Outcomes At A Single Centre.

BACKGROUND AND AIMS: Irreversible electroporation (IRE) is a non-thermal ablation technique for unresectable hepatocellular carcinoma (HCC) not amenable to standard thermal ablation. The aim of this study was to report our longer-term outcomes using this treatment modality. METHOD: We identified all patients at our institution who underwent IRE for HCC between December 2008 and October 2019 as recommended after multi-disciplinary team review. Demographic, clinical, tumour response and survival data up until 1 March, 2020 were analysed. The primary outcome was local recurrence-free survival (LRFS) in patients who had a complete response (CR). Secondary outcomes included CR rates, procedure-related complications and the incidence of death or liver transplantation. RESULTS: A total of 23 patients (78% males, median age 65.2 years) received IRE therapy to 33 HCC lesions during the study period with the median tumour size being 2.0 cm (range 1.0-5.0 cm). Twenty-nine (87.9%) lesions were successfully ablated after one (n = 26) or two (n = 3) procedures. The median follow-up time for these lesions was 20.4 months. The median overall LRFS was 34.5 (95% CI 24.8 -) months with a 6- and 12-month LRFS of 87.9% (95% CI 75.8-100) and 83.6% (95% CI 70.2-99.7), respectively. Tumours < 2 cm had a 12-month LRFS of 100% (95% CI 100-100). CONCLUSION: IRE appears to be an efficacious local ablative method for early stage HCC not amenable to standard ablative techniques, with very good CR rates and longer-term LRFS, particularly for smaller lesions. Further studies comparing this technique to more widely accepted ablative methods such as radiofrequency and microwave ablation are warranted.

Interleukin 3 directly stimulates both megakaryocyte progenitor cells and immature megakaryocytes.

A subset of stem cell antigen (sca-1)-positive mouse megakaryocyte progenitors was identified that correlates with other primitive precursors in bone marrow. The responsive bone marrow cells were obtained by depleting the marrow of cells bearing defined lineage markers (neutrophils, macrophages, and lymphoid cells) and enriched for primitive myeloid progenitor cells with high proliferative potential, selecting for cells expressing sca-1. The sca-1-positive megakaryocyte progenitors formed colonies in the presence of interleukin 3 (IL-3) alone. Immature megakaryocytes depleted of mature megakaryocytes and of cells expressing myeloid and lymphoid lineage markers were also responsive to IL-3. These data indicate that in the presence of high doses of IL-3, accessory cells are not obligatory for growth factor stimulation of megakaryocytopoiesis in vitro.

Proximal Versus Distal Splenic Artery Embolisation for Blunt Splenic Trauma: What is the Impact on Splenic Immune Function?

PURPOSE: To compare the impact of proximal or distal splenic artery embolisation versus that of splenectomy on splenic immune function as measured by IgM memory B cell levels. MATERIALS AND METHODS: Patients with splenic trauma who were treated by splenic artery embolisation (SAE) were enrolled. After 6 months splenic volume was assessed by CT, and IgM memory B cells in peripheral blood were measured and compared to a local normal reference population and to a post-splenectomy population. RESULTS: Of the 71 patients who underwent embolisation, 38 underwent proximal embolisation, 11 underwent distal embolisation, 22 patients were excluded, 1 had both proximal and distal embolisation, 5 did not survive and 16 did not return for evaluation. There was a significant difference between splenectomy and proximal or distal embolisation and a trend towards greater preservation of IgM memory B cell number in those with distal embolisation-a difference that could not be attributed to differences in age, grade of injury or residual splenic volume. CONCLUSION: IgM memory B cell levels are significantly higher in those treated with SAE compared to splenectomy. Our data provide evidence that splenic embolisation should reduce immunological complications of spleen trauma and suggest that distal embolisation may maintain better function.

Irreversible electroporation for unresectable hepatocellular carcinoma: initial experience and review of safety and outcomes.

The aims of this study were to evaluate the safety, feasibility and tumour response of _irreversible electroporation, a non-thermal ablation technique, for the treatment of unresectable hepatocellular carcinoma. The endpoints were safety and local treatment efficacy. Patients with unresectable tumours and tumours not amenable for radiofrequency _ablation because of their vicinity to organs vulnerable to thermal damage such as the bowel or because they were close to large blood vessels that would limit efficacy of ablation due to the heat sink effect were treated with irreversible electroporation using percutaneous _ultrasound and/or computed tomography guided electrode placement between November 2008 and _December 2009. Early, late, minor and major complications were recorded. Tumour response was determined on triphasic helical computed tomography follow-up at one month, then every three months post-procedure. Eleven patients received IRE therapy to 18 HCC lesions (Mean diameter 2.44 ± 0.99 cm; range 1.0-6.1 cm) with five patients having more than one treated HCC. Mean follow-up was 18 months (range 14-24 months). Six patients required repeat treatments for local residual or recurrent disease; two of these also had IRE for distant intrahepatic recurrence. No serious complications were observed despite seven lesions lying adjacent to important structures or organs. Four patients developed transient urinary retention and seven developed transient local post-procedure pain. After IRE therapy, 13 (72%) lesions were completely ablated with 93% success for lesions ≤ 3 cm (13/14). The local recurrence-free period was 18 ±â€…4 months and the distance recurrence free period was 14 ±â€…6 months. These preliminary results suggest that IRE is a safe and feasible technique for local ablation of HCC, particularly for lesions less than 3 cm. No major complications were encountered during this study even for tumours close to essential structures or organs.

Initial experience in 115 patients with the retrievable Cook Celect vena cava filter.

The aim of this study was to evaluate our experience with the retrievable Cook Celect inferior vena cava (IVC) filter (William Cook, Europe) with regard to insertion, efficiency, ease of retrieval, and any associated complications. A retrospective review was performed of 115 patients (41 female, 74 male, mean age 47.97 years) who underwent Cook Celect IVC filter insertion between December 2005 and October 2007. Filter insertion was successful in all patients. Of the 115 filters inserted, 57 have been successfully retrieved (49.6%) to date. The successful retrieval rate from attempted retrieval was 93.4%. The mean dwell time of successfully retrieved filters was 114.9 days (range 14-267 days). Failed retrievals were due to a thrombosed vena cava (n = 1) and endothelialisation of the filter (n = 3). In the failed retrieval group the mean implantation time was 142 days (range 78-211 days). While this is the first retrospective clinical study on the Cook Celect filter, results to date are promising. We demonstrated an efficacious filter with a high successful retrieval rate of 93.4% and a low complication rate. The filter was assessed with extended dwell times (range 14-267 days). Failed retrieval secondary to hook endothelialisation continues to be an issue with this filter. We recognize that a limitation of our study was the lack of systematic follow-up for clinically silent complications. Further studies to evaluate longer term outcomes and effectiveness of this filter are warranted.

Recombinant rat stem cell factor stimulates the amplification and differentiation of fractionated mouse stem cell populations.

The role of recombinant rat stem cell factor (rrSCF) was studied on defined primitive bone marrow cell populations. In agar culture of 500 lineage-negative/Sca-1-positive (Lin-/Sca-1+) cells, rrSCF alone stimulates small colonies of predominantly granulocytic cells. The combinations of rrSCF plus interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or macrophage CSF (CSF-1) stimulated primitive progenitor cells defined as high proliferative potential colony-forming cells (HPP-CFC). Synergistic increases in total colony numbers were obtained with rrSCF plus GM-CSF, granulocyte CSF (G-CSF), CSF-1, or IL-6, but not IL-1 or IL-3. Lin-/Sca-1+ cells were incubated in liquid culture at 3,000 cells/mL for 6 days in the presence of rrSCF alone or in combination with other growth factors. The total number of cells was increased twofold in the presence of rrSCF, with the progeny primarily myeloid in nature. The greatest increase in cell number was obtained with rrSCF plus IL-3, where the cell number increased 40-fold. These factors also stimulated an increase in HPP-CFC (10-fold) and GM-CFC (500-fold). To determine if these interactions were direct, single Lin-/Sca-1+ cells were sorted into microtiter wells and the cell proliferation scored 6 days later. RrSCF synergized with IL-3, IL-6, and G-CSF to stimulate the proliferation of single cells. The cells in positive wells were subcultured into colony-forming assays and up to 400 CFC per well were obtained after 14 days incubation of the secondary cultures. These data demonstrate that rrSCF acts in combination with various growth factors to directly stimulate the amplification potential of hematopoietic primitive precursors, resulting in differentiation of these precursors.

The role of interleukin 6 in megakaryocyte formation, megakaryocyte development and platelet production.

Megakaryocytopoiesis is the cellular amplification and differentiation of precursors into immature megakaryocytes, and the cytoplasmic maturation of these megakaryocytes, a process terminating in the release of platelets into the circulation. Interleukin 6 (IL-6) stimulates megakaryocytopoiesis in the bone marrow, increasing platelet numbers in the circulation. IL-6 alone is poorly active on the growth of stem cell populations, but acts in synergy with stem cell factor (c-kit ligand) to expand the committed myeloid progenitor compartments but not the megakaryocyte progenitors. IL-6 has a direct action on megakaryocyte progenitors but only in synergy with low doses of interleukin 3 (IL-3), increasing the number of immature megakaryocytes and enhancing the processes of development into mature megakaryocytes. IL-6 is about 10 times more active on megakaryocytes than on megakaryocyte progenitors in cell culture. It is active alone and will stimulate increases in cell size and DNA content. IL-6 does not appear to stimulate the process of platelet release. IL-6 is found in bone marrow, in both macrophage subsets and megakaryocytes, indicating that it may be an important physiological regulator of both paracrinal (microenvironmental) and autocrinal mechanisms controlling megakaryocyte development in bone marrow.