Selective internal radiation therapy (SIRT) for hepatocellular carcinoma (HCC): informing clinical practice for multidisciplinary teams in England.

Objective: Hepatocellular carcinoma (HCC) deaths are rising alarmingly. Many patients are unsuitable for available therapies. Poor response rates further hamper outcomes for those that are. Selective internal radiation therapy (SIRT) offers hope, although which patients benefit over standard approaches remains unclear. Design/method: As a quality/service improvement, we audited consecutive patients treated with SIRT (2015-2020) by the Newcastle upon Tyne Hospitals National Health Service Foundation Trust HCC multidisciplinary team. Indications, Barcelona clinic liver cancer (BCLC) stage, treatment response, subsequent therapies and survival at 30 September 2021 were assessed. Results: Fifty-one patients received SIRT. Thirty-day mortality was zero. Three months partial response, stable disease and progressive disease on imaging were 50%, 22% and 28%, respectively. Overall median survival was 21 months. There were four subgroups: (1) BCLC-B: HCC>7 cm too large for transarterial chemoembolisation (TACE) alone (n=21); (2) BCLC-B: HCC progressed post TACE (n=7); (3) BCLC-C: HCC with any combination of large tumour burden, branch portal vein thrombosis, non-hepatitis C virus aetiology (n=16); (4) BCLC-C: sorafenib inappropriate (n=7). In group 1, 5/21 (23.8%) of patients were downstaged to resection, 33% received subsequent medical therapies and median survival was >40 months. In BCLC-B patients treated second line (group 2), median survival was 14.2 months. In BCLC-C, median survival was 20.2 months for group 3 and 4.2 months for group 4. Conclusion: SIRT outcomes for advanced HCC, often bridging patients with adverse predictive factors to subsequent surgery or medical therapies, were encouraging. A role after TACE or for BCLC-C patients requires further assessment.

A Multi-centre, Single Arm, Non-randomized, Prospective European Trial to Evaluate the Safety and Efficacy of the HistoSonics System in the Treatment of Primary and Metastatic Liver Cancers (#HOPE4LIVER).

PURPOSE: Image-guided thermal ablation are established treatment options for non-surgical patients with primary and metastatic liver cancers. However, there are limitations with nonuniformity of cancer tissue destruction, heat sink effect and the risk of thermal ablative injury. The current non-thermal ablative techniques have high risk of local recurrence and are not widely adopted. Histotripsy is a treatment technology that destroys targeted tissue under ultrasound visualization via mechanical destruction through the precise application of acoustic cavitation and can offer the potential of non-invasive, non-thermal and non-ionizing radiation cancer treatment. The aim of this multi-centre non-randomized phase I/II trial is to assess the initial safety and efficacy of the prototype investigational 'System' in the treatment of primary and metastatic liver cancers. METHODS/DESIGN: All non-surgical patients with primary/metastatic liver cancers having had previous liver directed therapy, radiation therapy or image-guided ablation may be offered image-guided Histotripsy as per trial protocol. The co-primary endpoints are technical success and procedural safety. Technical success is determined, at ≤ 36 h post procedure, by evaluating the histotripsy treatment size and coverage. The procedural safety is defined by procedure related major complications, defined as Common Terminology Criteria for Adverse Events (CTCAE version 5) grade 3 or higher toxicities, up to 30 days post procedure. This phase I/II trial has intended to recruit up to 45 patients to show safety and efficacy of image-guided histotripsy in liver cancers. TRAIL REGISTRATION: Clinicaltrials.gov identifier-NCT04573881; NIHR CRN CPMS-ID 47572.

Treatment of unresectable locally advanced pancreatic cancer with percutaneous irreversible electroporation (IRE) following initial systemic chemotherapy (LAP-PIE) trial: study protocol for a feasibility randomised controlled trial.

BACKGROUND: Approximately 30% of patients with pancreas cancer have unresectable locally advanced disease, which is currently treated with systemic chemotherapy. A new treatment option of irreversible electroporation (IRE) has been investigated for these patients since 2005. Cohort studies suggest that IRE confers a survival advantage, but with associated, procedure-related complications. Selection bias may account for improved survival and there have been no prospective randomised trials evaluating the harms and benefits of therapy. The aim of this trial is to evaluate the feasibility of a randomised comparison of IRE therapy with chemotherapy versus chemotherapy alone in patients with locally advanced pancreatic cancer (LAPC). METHODS AND ANALYSIS: Eligible patients with LAPC who have undergone first-line 5-FluoroUracil, Leucovorin, Irinotecan and Oxaliplatin chemotherapy will be randomised to receive either a single session of IRE followed by (if indicated) further chemotherapy or to chemotherapy alone (standard of care). Fifty patients from up to seven specialist pancreas centres in the UK will be recruited over a period of 15 months. Trial follow-up will be 12 months. The primary outcome measure is ability to recruit. Secondary objectives include practicality and technical success of treatment, acceptability of treatment to patients and clinicians and safety of treatment. A qualitative study has been incorporated to evaluate the patient and clinician perspective of the locally advanced pancreatic cancer with percutaneous irreversible electroporation trial. It is likely that the data obtained will guide the structure, the primary outcome measure, the power and the duration of a subsequent multicentre randomised controlled trial aimed at establishing the clinical efficiency of pancreas IRE therapy. Indicative procedure-related costings will be collected in this feasibility trial, which will inform the cost evaluation in the subsequent study on efficiency. ETHICS AND DISSEMINATION: The protocol has received approval by London-Brent Research Ethics Committee reference number 21/LO/0077.Results will be analysed following completion of trial recruitment and follow-up. Results will be presented to international conferences with an interest in oncology, hepatopancreaticobiliary surgery and interventional radiology and be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN14986389.

COVID-19 and liver cancer: lost patients and larger tumours.

BACKGROUND: Northern England has been experiencing a persistent rise in the number of primary liver cancers, largely driven by an increasing incidence of hepatocellular carcinoma (HCC) secondary to alcohol-related liver disease and non-alcoholic fatty liver disease. Here we review the effect of the COVID-19 pandemic on primary liver cancer services and patients in our region. OBJECTIVE: To assess the impact of the COVID-19 pandemic on patients with newly diagnosed liver cancer in our region. DESIGN: We prospectively audited our service for the first year of the pandemic (March 2020-February 2021), comparing mode of presentation, disease stage, treatments and outcomes to a retrospective observational consecutive cohort immediately prepandemic (March 2019-February 2020). RESULTS: We observed a marked decrease in HCC referrals compared with previous years, falling from 190 confirmed new cases to 120 (37%). Symptomatic became the the most common mode of presentation, with fewer tumours detected by surveillance or incidentally (% surveillance/incidental/symptomatic; 34/42/24 prepandemic vs 27/33/40 in the pandemic, p=0.013). HCC tumour size was larger in the pandemic year (60±4.6 mm vs 48±2.6 mm, p=0.017), with a higher incidence of spontaneous tumour haemorrhage. The number of new cases of intrahepatic cholangiocarcinoma (ICC) fell only slightly, with symptomatic presentation typical. Patients received treatment appropriate for their cancer stage, with waiting times shorter for patients with HCC and unchanged for patients with ICC. Survival was associated with stage both before and during the pandemic. 9% acquired COVID-19 infection. CONCLUSION: The pandemic-associated reduction in referred patients in our region was attributed to the disruption of routine healthcare. For those referred, treatments and survival were appropriate for their stage at presentation. Non-referred or missing patients are expected to present with more advanced disease, with poorer outcomes. While protective measures are necessary during the pandemic, we recommend routine healthcare services continue, with patients encouraged to engage.

Margin Accentuation Irreversible Electroporation in Stage III Pancreatic Cancer: A Systematic Review.

The present systematic review aimed to summarise the available evidence on indications and oncological outcomes after MA IRE for stage III pancreatic cancer (PC). A literature search was performed in the Pubmed, MEDLINE, EMBASE, SCOPUS databases using the PRISMA framework to identify all MA IRE studies. Nine studies with 235 locally advanced (LA) (82%, 192/235) or Borderline resectable (BR) PC (18%, 43/235) patients undergoing MA IRE pancreatic resection were included. Patients were mostly male (56%) with a weighted-mean age of 61 years (95% CI: 58-64). Pancreatoduodenectomy was performed in 51% (120/235) and distal pancreatectomy in 49% (115/235). R0 resection rate was 73% (77/105). Clavien Dindo grade 3-5 postoperative complications occurred in 19% (36/187). Follow-up intervals ranged from 3 to 29 months. Local and systematic recurrences were noted in 8 and 43 patients, respectively. The weighted-mean progression free survival was 11 months (95% CI: 7-15). The weighted-mean overall survival was 22 months (95% CI 20-23 months) and 8 months (95% CI 1-32 months) for MA IRE and IRE alone, respectively. Early non-randomised data suggest MA IRE during pancreatic surgery for stage III pancreatic cancer may result in increased R0 resection rates and improved OS with acceptable postoperative morbidity. Further, larger studies are warranted to corroborate this evidence.

Treatment strategies for early stage hepatocellular carcinoma: a systematic review and network meta-analysis of randomised clinical trials.

BACKGROUND: Several treatment strategies for early stage hepatocellular cancers (HCC) have been evaluated in randomised controlled trials (RCTs). This network meta-analysis (NMA) aimed to explore the relative effectiveness of these different approaches on their impact on overall (OS) and recurrence-free survival (RFS). METHODS: A systematic review was conducted to identify RCT's reported up to 23rd January 2020. Indirect comparisons of all regimens were simultaneously compared using random-effects NMA. RESULTS: Twenty-eight RCT's, involving 3,618 patients, reporting 13 different treatment strategies for early stage HCC were identified. Median follow-up, reported in 22 studies, ranged from 12-93 months. In this NMA, RFA in combination with iodine-125 was ranked first for both RFS (HR: 0.50, 95% CI: 0.19-1.31) and OS (HR: 0.41, 95% CI: 0.19-0.94). In subgroup with solitary HCC, lack of studies reporting RFS precluded reliable analysis. However, RFA in combination with iodine-125 was associated with markedly better OS (HR: 0.21, 95% CI: 0.05-0.93). CONCLUSION: This NMA identified RFA in combination with iodine-125 as a treatment delivering better RFS and OS, in patients with early stage HCC, especially for those with solitary HCC. This technique warrants further evaluation in both Asia and Western regions.

Liver Resection After Selective Internal Radiation Therapy with Yttrium-90: Safety and Outcomes.

INTRODUCTION: Selective internal radiotherapy (SIRT) with yttrium-90 (Y-90) is an intra-arterial therapy for hepatic malignancy in patients who are unsuitable for surgical resection. This treatment is considered palliative, although some patients can demonstrate a response that is adequate to facilitate surgical resection with curative intent. METHODS: All patients who underwent liver resection post SIRT were reviewed. Data gathered included patient demographics, tumor type, surgical details, and post-operative outcomes. RESULTS: Twelve patients underwent SIRT followed by liver resection (7 males and 5 females). Pathologies were hepatocellular carcinoma (n = 5), metastatic colorectal cancer (n = 5), and neuroendocrine tumor (n = 2). Lesional response (size, volume, and RECIST (response evaluation criteria in solid tumors)) was calculated and where appropriate functional liver remnant (FLR) is presented. Mean FLR increase was 264cm3 (range - 123 to 909), and all cases demonstrated a partial response according to RECIST with a mean largest lesion volume reduction of 475cm3 (range 14-1632). No post-SIRT complications were noted. Hepatectomy occurred at a mean of 322 days from SIRT treatment. Ninety-day morbidity was 67% (n = 6), complications post-surgery were analyzed according to the Clavien-Dindo classification scale; a total of 15 events occurred in 6 patients. Ninety-day mortality of 11% (n = 1). CONCLUSION: In selected cases, liver resection is possible post SIRT. As this can represent a potentially curative option, it is important to reconsider resection in the follow-up of patients undergoing SIRT. Post-operative complications are noted following major and extended liver resection. Therefore, further studies are needed to improve patient selection.

Early Experience of Trans-arterial Chemo-Embolisation for Hepatocellular Carcinoma with a Novel Radiopaque Bead.

AIMS: To evaluate early outcomes of patients with hepatocellular carcinoma (HCC) treated with a novel radiopaque bead, the 75-150 µm DC Bead LUMI™ (Biocompatibles UK Ltd). MATERIALS AND METHODS: This was a retrospective review of the first 40 consecutive patients at a UK tertiary hepato-biliary centre, treated for HCC with TACE using radiopaque beads, between May 2017 and March 2019. Information regarding complications, mortality, lesion response and subsequent ablation procedures was collected from electronic records and case notes. Intra- and post-operative imaging was reviewed for visibility of the embolised territory. RESULTS: Fifty-five TACE procedures were performed in 40 patients, with a median age of 70 years (range 28-88) and median lesion size of 3.8 cm (range 1.5-7.8). The median follow-up period was 30 weeks (range 6-101). Mean post-procedure hospital stay was 1.2 days. Complications of CIRSE Grade II or above occurred after 4/55 procedures (7.3%). Mortality at 30 days was zero. Objective response rates (mRECIST) at 1, 3 and 6 months were 32/35 (91.4%), 21/24 (87.5%) and 12/15 (80%), respectively. Complete response rates at 1, 3 and 6 months were 16/35 (45.7%), 12/24 (50%) and 9/15 (60%). The embolised territory was visible on intra-operative and follow-up CT imaging in all patients. The radiopaque beads were used as a fiducial marker to guide ablation in 5/40 patients (12.5%). CONCLUSION: TACE with radiopaque beads shows promising tolerability and efficacy. The radiopaque beads ensure visualisation of the embolised lesion on intra- and post-operative imaging and, in selected cases, can act as a marker for CT-guided ablation.

Percutaneous Irreversible Electroporation (IRE) of Hepatic Malignancy: A Bi-institutional Analysis of Safety and Outcomes.

AIM: Irreversible electroporation (IRE) is a non-thermal ablative option in patients unsuitable for standard thermal ablation, due to its potential to preserve collagenous structures (vessels and ducts) and a reduced susceptibility to heat sink effects. In this series from two large tertiary referral hepatobiliary centres, we aim to assess the safety/outcomes of hepatic IRE. MATERIALS AND METHODS: Bi-institutional retrospective, longitudinal follow-up series of IRE for primary hepatic malignancy; [hepatocellular carcinoma (n = 20), cholangiocarcinoma (n = 3)] and secondary metastatic disease; colorectal (n = 28), neuroendocrine (n = 1), pancreatic (n = 1), breast (n = 1), gastrointestinal stromal tumour (GIST, n = 1) and malignant thymoma (n = 1). Outcome measures included procedural safety/effectiveness, time to progression and time to death. RESULTS: Between 2013 and 2017, 52 patients underwent percutaneous IRE of 59 liver tumours in 53 sessions. All tumours were deemed unsuitable for thermal ablation. Cases were performed using ultrasound (US) or computed tomography (CT) guidance. A complete ablation was achieved in n = 44, (75%) of cases with an overall complication rate of 17% (n = 9). Of the complete ablation group, median time to progression was 8 months. At 12 months, 44% were progression-free (95% CI 30-66%). The data suggest that larger lesion size (> 2 cm) is associated with shorter time to progression and there is highly significant difference with faster time to progression in mCRC compared with HCC. Median survival time was 38 months. CONCLUSION: This bi-institutional review is the largest UK series of IRE and suggests this ablative technology can be a useful tool, but appears to mainly induce local tumour control rather than cure with HCC having better outcomes than mCRC.

Fibrolamellar Hepatocellular Carcinoma: Treatment with Yttrium-90 and Subsequent Surgical Resection.

We describe a 52-year-old female patient who presented with a 9.5-cm fibrolamellar hepatocellular carcinoma (FL-HCC). The patient was initially unsuitable for surgical resection and therefore underwent transarterial chemoembolization followed by selective internal radiation therapy (SIRT) with Yttrium-90 to downsize the tumour. Following SIRT, the tumour decreased in volume from 350 to 20 cm3 allowing curative (R0) resection with an extended left hepatectomy and reconstruction of IVC. This is the first reported case of FL-HCC treated with SIRT in which, due to the good SIRT response, the patient was downsized to allow curative resection.

Simulation of endovascular guidewire behaviour and experimental validation.

Guidewire manipulation is a core skill in endovascular interventional radiology procedures. Simulation-based training offers a valuable alternative for mastering these skills, but requires a faithful replication of complex guidewire behaviour inside the vasculature. This paper presents the integration of real flexural modulus (FM) measurements into our guidewire model that mimics the flexibility of standard guidewires. The variation of FM along the length of each wire was determined for seven commonly used guidewires using a three-point bending test for the main body and a two-point bending test for the flexible end. Guidewire FM values were then attributed to seven different models, each formed by a series of particles connected by links of variable FM and replicating the flexible end shape. The FM integration was done through a trial and error process matching real FM to virtual bending coefficient. This mass-spring representation captures the required range of behaviour and enables accurate deformation within virtual vasculature.

Guidewire and catheter behavioural simulation.

Guidewire and catheter manipulation is a core skill in endovascular interventional radiology. It is usually acquired in an apprenticeship on patients, but this training is expensive and risky. Simulation offers an efficient alternative for core skills training, though the instrument complex behaviour requires accurate replication. This paper reviews the mass-spring model used to simulate seven guidewires and three catheters, and the matching with their real world counterparts by tuning our model's bending coefficient, which allows replication of the instrument flexibility. This coefficient was matched through computed tomography imaging of a vascular phantom in which each instrument was inserted and manipulated. With an average distance of 2.27 mm (standard deviation: 1.54) between real and virtual instruments, our representation showed realistic behaviour.

Early experience with the Amplatzer Vascular Plug II for occlusive purposes in arteriovenous hemodialysis access.

The Amplatzer Vascular Plug Type II (AVP II) has proven effective in the therapeutic embolization of various vascular lesions. It benefits from very rapid occlusion of the target lesion and can be deployed, retrieved, and redeployed if required. There is no literature available on use of the AVP II in the maintenance, closure, and management of complicated arteriovenous access in hemodialysis patients. In this series, we present our clinical experience with the use of the AVP II for embolization of problematic hemodialysis access. The AVP II is a self-expandable Nitinol wire-mesh device. Mounted on a delivery wire it has the capability to be deployed, recaptured, and redeployed. In total seven patients (four males: one diabetic, all nonsmokers), with ages ranging from 44 to 81 years (mean, 63 years), were treated between July 2008 and January 2009. One patient had not started dialysis. The remaining six patients had varied histories, with the time on hemodialysis ranging from 1 to 21 years. Retrospective review of clinical notes revealed patient demographics, type of access, device size, deployment site, and outcomes. Indications for embolization included steal syndrome (one patient), high-flow tributaries (two patients), and limb swelling (four patients). All patients had clinical and sonographical follow-up to 3 months. Surgical ligation had either failed, was considered a contraindication due to concerns regarding wound healing, or was considered difficult due to complex venous anatomy. Only one device was used in each patient, ranging from 6 to 16 mm in diameter. Immediate technical success was seen in 100%. All these patients were followed up clinically in the vascular access radiology clinic at 4 weeks and 3 months. Occlusion of the treated vessel and resolution of symptoms were reconfirmed in 100% of cases at 3 months. It was also noted whether patients were having successful dialysis, if required. There were no complications. Average procedural time was 19 min. We conclude that the AVP II is an efficient, safe, and technically simple occlusion device for use in arteriovenous access.

A retrospective comparative study of tunneled haemodialysis catheters inserted through occluded or collateral veins versus conventional methods.

Tunneled hemodialysis catheters become essential in dialysis access when there is no possibility of using a functioning arteriovenous fistula. Collateral or occluded veins visible on ultrasound are used for puncture and passage of catheters into the central venous system. Chronically occluded veins are crossed with guidewires to allow dilatation and subsequent passage of hemodialysis catheters. We performed a retrospective analysis of patient demographics, comorbidities, procedural complications, functional survival, performance, and history of previous vascular access. The study group was compared with two control groups in which dialysis catheters were inserted either by radiologists in the interventional suite or by clinicians on the wards. Nineteen patients from the study group were compared with same number of patients in both control groups. The mean age of the study group was higher compared with the control groups. There was no significant difference in mean functional survival, infection rates, dialysis pump speeds in the first 2 weeks, and procedural complications between the study group and the controls. The study group had a significantly higher number of previous vascular access interventions, longer dialysis careers, and more comorbidities. Tunneled dialysis catheter placement by way of collateral or occluded veins appears safe and effective. These techniques give the operator further options when faced with patients possessing challenging vascular access. Indeed, there may be a case for preferential use of these veins to keep patent central veins in reserve.

Cost effective ultrasound imaging training mentor for use in developing countries.

This paper reports on a low cost system for training ultrasound imaging techniques. The need for such training is particularly acute in developing countries where typically ultrasound scanners remain idle due to the lack of experienced sonographers. The system described below is aimed at a PC platform but uses interface components from the Nintendo Wii games console. The training software is being designed to support a variety of patient case studies, and also supports remote tutoring over the internet.

AngioJet thrombectomy for occluded dialysis fistulae: outcome data.

This study evaluates AngioJet thrombectomy of occluded autogenous dialysis fistulae and polytetrafluoroethylene (PTFE) grafts in a UK hemodialysis population. Comparison is made with published data of alternative percutaneous thrombectomy methods. All patients with occluded dialysis fistulae who sought care at the Royal Liverpool University Hospital between October 2006 and June 2008 were included in the study. All patients were treated with the AngioJet Rheolytic Thrombectomy Device (Possis, Minneapolis, MN). Demographics, time of occlusion, adjunctive therapies, complications, and follow-up data have been prospectively recorded. A total of 64 thrombectomy procedures were performed in 48 patients. Forty-four autogenous fistulas were treated in 34 patients (19 brachiocephalic, 8 radiocephalic, and 7 transposed brachiobasilic). Twenty PTFE grafts were treated in 14 patients (9 brachioaxillary, 3 brachiocephalic loop grafts, 1 brachiobasilic, and 1 femoro-femoral). The average length of occlusion was 24 cm. Average time to intervention was 4 days. Immediate primary patency was 91%. Primary patency at 1, 3, and 6 months, respectively, was 71%, 60%, and 37%. Secondary patency at 3, 6, and 12 months was 87%, 77%, and 62%, respectively. Angioplasty was carried out in all procedures. Patients required stent insertion in 34 of the 64 thrombectomies to treat angioplasty-resistant stenoses. Complications included a puncture-site hematoma, and three angioplasty-related vein ruptures in one patient, all treated with covered stent grafts. Two cases of distal brachial arterial embolization were successfully treated by thrombosuction. AngioJet thrombectomy in dialysis access occlusion is safe and effective, comparing favorably with other methods.

Implications of computer tomography measurement in the management of renal tumours.

BACKGROUND: To compare radiographic measurement and pathological measurement of renal tumours to see if there was a significant difference between the two as this may have implications in the management. METHODS: We retrospectively analyzed CT measurements of 106 consecutive patients who underwent either radical or nephron sparing surgery in our institution and compared this to the actual measurement of the surgical specimen. The largest axial measurement was compared as this is the primary consideration before offering either treatment modality. RESULTS: The mean age of the patients was 64 years (range 31-92). There were 76 males and 30 females. The median tumour size was 70 mm (range 16-175) on CT and 65 mm (range 15-90) on pathological measurement. 25 patients had a CT size < or = 40 mm. CT tended to overestimate the size of tumours in 41 patients, underestimate in 45 and agree with surgical size in 20 patients. Statistically there was no significant difference between the two measurements (p = 0.7, Wilcoxon sign ranked test). When subdivided into tumours less than 40 mm (p = 0.7) and more than 40 mm (p = 0.09) again there was no statistically significant difference between the two measurements. However in 5(5%) patients who were not offered nephron sparing surgery based on CT findings (size > 40 mm) the pathological size was < or = 40 mm (p = < 0.001, Fishers Exact test). Pathologically the tumours were classified as renal cell carcinoma (n = 98), angiomyolipoma (3), and oncocytoma (5). CONCLUSION: CT measurement of renal tumour size correlates well with the actual size of the tumour. However CT does tend to overestimate the size in a small number of patients which may have a bearing on the modality of treatment offered.