EMBIO trial study protocol: left gastric artery embolisation for weight loss in patients living with obesity with a BMI 35-50 kg/m2.

INTRODUCTION: Left gastric artery embolisation (LGAE) is a well-established treatment for major upper gastrointestinal (GI) bleeding when control is not established via upper GI endoscopy and recently has shown promising results for weight loss in small single arm studies. LGAE could be a treatment option in between our current tier-3 and tier-4 services for obesity. EMBIO is a National Institute for Health Research funded trial, a multicentre double-blinded randomised controlled trial between Imperial College National Health Service Trust and University College London Hospital, comparing LGAE versus Placebo procedure. The key aims of the trial is to evaluate LGAE efficacy on weight loss, its mechanism of action, safety profile and obesity-related comorbidities. METHODS AND ANALYSIS: 76 participants will be recruited from the existing tier-3 database after providing informed consent. Key inclusion criteria include adults aged 18-70 with a body mass index 35-50 kg/m2 and appropriate anatomy of the left gastric artery and coeliac plexus on CT Angiogram. Key exclusion criteria included previous major abdominal and bariatric surgery, weight >150 kg, type 2 diabetes on any medications other than metformin and the use of weight modifying medications. Participants will undergo mechanistic visits 1 week prior to the intervention and 3, 6 and 12 months postintervention. Informed consent will be received from each participant and they will be randomised in a 1:1 ratio to left gastric artery embolisation and placebo treatment. Blinding strategies include the use of moderate doses of sedation, visual and auditory isolation. All participants will enter a tier-3 weight management programme postintervention. The primary analysis will estimate the difference between the groups in the mean per cent weight loss at 12 months. ETHICS AND DISSEMINATION: This trial shall be conducted in full conformity with the 1964 Declaration of Helsinki and all subsequent revisions. Local research ethics approval was granted by London-Central Research Ethics Committee, (Reference 19/LO/0509) on 11 October 2019. The Medicines and Healthcare products Regulatory Agency (MHRA) issued the Letter of No Objection on 8 April 2022 (Reference CI/2022/0008/GB). The trial's development and progress are monitored by an independent trial steering committee and data monitoring and ethics committee. The researchers plan to disseminate results at conferences, in peer- reviewed journals as well as lay media and to patient organisations. TRIAL REGISTRATION NUMBER: ISRCTN16158402.

Phase 0 Study of Vandetanib-Eluting Radiopaque Embolics as a Preoperative Embolization Treatment in Patients with Resectable Liver Malignancies.

PURPOSE: To assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemoembolization (TACE) in patients with resectable liver malignancies. MATERIALS AND METHODS: The VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years and had resectable hepatocellular carcinoma (HCC) (Child-Pugh A) or metastatic colorectal cancer (mCRC). Patients received 1 mL of BTG-002814 transarterially (containing 100 mg of vandetanib) 7-21 days prior to surgery. The primary objectives were to establish the safety and tolerability of BTG-002814 and determine the concentrations of vandetanib and the N-desmethyl vandetanib metabolite in the plasma and resected liver after treatment. Biomarker studies included circulating proangiogenic factors, perfusion computed tomography, and dynamic contrast-enhanced magnetic resonance imaging. RESULTS: Eight patients were enrolled: 2 with HCC and 6 with mCRC. There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days after treatment, with a mean maximum concentration of 24.3 ng/mL (standard deviation ± 13.94 ng/mL), and in resected liver tissue up to 32 days after treatment (441-404,000 ng/g). The median percentage of tumor necrosis was 92.5% (range, 5%-100%). There were no significant changes in perfusion imaging parameters after TACE. CONCLUSIONS: BTG-002814 has an acceptable safety profile in patients before surgery. The presence of vandetanib in the tumor specimens up to 32 days after treatment suggests sustained anticancer activity, while the low vandetanib levels in the plasma suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies.

Radiopaque drug-eluting embolisation beads as fiducial markers for stereotactic liver radiotherapy.

OBJECTIVE: To determine the feasibility of using radiopaque (RO) beads as direct tumour surrogates for image-guided radiotherapy (IGRT) in patients with liver tumours after transarterial chemoembolisation (TACE). METHODS: A novel vandetanib-eluting RO bead was delivered via TACE as part of a first-in-human clinical trial in patients with either hepatocellular carcinoma or liver metastases from colorectal cancer. Following TACE, patients underwent simulated radiotherapy imaging with four-dimensional computed tomography (4D-CT) and cone-beam CT (CBCT) imaging. RO beads were contoured using automated thresholding, and feasibility of matching between the simulated radiotherapy planning dataset (AVE-IP image from 4D data) and CBCT scans assessed. Additional kV, MV, helical CT and CBCT images of RO beads were obtained using an in-house phantom. Stability of RO bead position was assessed by comparing 4D-CT imaging to CT scans taken 6-20 days following TACE. RESULTS: Eight patients were treated and 4D-CT and CBCT images acquired. RO beads were visible on 4D-CT and CBCT images in all cases and matching successfully performed. Differences in centre of mass of RO beads between CBCT and simulated radiotherapy planning scans (AVE-IP dataset) were 2.0 mm mediolaterally, 1.7 mm anteroposteriorally and 3.5 mm craniocaudally. RO beads in the phantom were visible on all imaging modalities assessed. RO bead position remained stable up to 29 days post TACE. CONCLUSION: RO beads are visible on IGRT imaging modalities, showing minimal artefact. They can be used for on-set matching with CBCT and remain stable over time. ADVANCES IN KNOWLEDGE: The role of RO beads as fiducial markers for stereotactic liver radiotherapy is feasible and warrants further exploration as a combination therapy approach.

Dual-modality emergency management of a rare cause of an aorto-oesophageal fistula: a case report.

Aorto-oesophageal fistula (AOF) is a life-threatening condition that usually presents with upper gastro-intestinal haemorrhage. This case report details the emergency presentation and management of a 51-year-old male who presented with hematemesis secondary to an impacted denture (ingested two years previously) in the oesophagus that had led to an AOF. This necessitated urgent thoracic endovascular aortic repair followed by thoracotomy, oesophagotomy, T-tube insertion and oesophagostomy. This is the first documentation in the literature of the dual-modality management for this rare cause of AOF and demonstrates the multidisciplinary approach to successful management of this complex yet rare presentation.

Erectile Dysfunction in Peripheral Vascular Disease: Endovascular Revascularization as a Potential Therapeutic Target.

INTRODUCTION: Erectile dysfunction (ED) affects more than 150 million men worldwide, with deleterious effects on quality of life. ED is known to be associated with ischemic heart disease but the impact of ED in patients with peripheral arterial disease (PAD) is unknown. We assessed the prevalence and severity of ED in patients with PVD. METHODS: Following ethical approval, sequential male patients diagnosed with PAD over a 1-year period following diagnosis of intermittent claudication. The patient demographics and comorbidities were recorded, with the International Index of Erectile Function (IIEF-5) questionnaire used to grade severity of ED. Computed tomographic angiography and severity of stenosis in the proximal vessels and internal pudendal arteries were correlated using a modified Bollinger Matrix scoring system. RESULTS: 60 patients were recruited, most (77.2%) reported erectile dysfunction (52.5% severe, 22.5% moderate). Patients with severe ED were more likely to have 2 or more comorbidities (P = .009). 86.7% with severe ED had bilateral internal pudendal artery stenosis with a mean modified Bollinger score of 17.6. 35.5% of moderate ED patients had bilateral internal pudendal stenosis with a mean Bollinger score of 11.75. There was significant difference in overall scores between moderate and severe erectile dysfunction (p< 0.05), thus indicating a potential link between ED severity and extent of vessel stenosis. CONCLUSION: There is a substantial burden of clinically significant ED among patients with PAD. This study suggests ED should be discussed with all PAD patients and ED may precede a PAD diagnosis. There is scope for endovascular revascularization as a treatment option for ED secondary to arterial insufficiency.

Management of acute and chronic iliofemoral venous outflow obstruction: a multidisciplinary team consensus.

The aim of this manuscript was to establish a consensus for the management of acute and chronic venous obstruction among specialists in the UK. Specialist physicians representing vascular surgery, interventional radiology and hematology were invited to 3 meetings to discuss management of acute and chronic iliofemoral obstruction. The meetings outlined controversial areas, included a topic-by-topic review; and on completion reached a consensus when greater than 80% agreement was reached on each topic. Physicians from 19 UK hospitals agreed on treatment protocols and highlighted areas that need development. Potential standard treatment algorithms were created. It was decided to establish a national registry of venous patients led by representatives from the treating multidisciplinary teams. Technical improvements have facilitated invasive treatment of patients with acute and chronic venous obstruction; however, the evidence guiding treatment is weak. Treatment should be conducted in centers with multi-disciplinary input; robust, coordinated data collection; and regular outcome analysis to ensure safe and effective treatment and a basis for future evolvement.

Standardisation of Technique and Volume of Iodinated Contrast Administration During Infrainguinal Angioplasty.

BACKGROUND: Acute Kidney injury is recognised to occur after administration of iodinated contrast during endovascular interventions for peripheral arterial disease. There are no standardised protocols for contrast delivery during infrainguinal angiography. OBJECTIVE: The objective of this paper is to review published practice regarding the technique of conventional infrainguinal angiography and intervention, and describe a standard set of subtraction views, injection rates and contrast volumes for infrainguinal angioplasty. METHODS: Database searches and review of papers containing (Angioplasty or Angiography) and ("lower limb" or peripheral or infrainguinal) and (method or technique or guidelines or protocol) was performed and defined procedures assessed. RESULTS: A small number of papers provided specific technical details relating to contrast volumes and angiography views. There was considerable variation from authors who have described the contrast volumes used for lower limb angiography. We describe our simple and consistent method. The precise pathophysiology of contrast related nephropathy is under scrutiny. There is interest in new technology to minimise contrast induced kidney injury. CONCLUSION: Few publications specify iodinated contrast doses, injection volumes or imaging views for infrainguinal arteriography. Standard infrainguinal angioplasty can be performed with conventional equipment using relatively small volumes of contrast by following a systematic technique.

VEROnA Protocol: A Pilot, Open-Label, Single-Arm, Phase 0, Window-of-Opportunity Study of Vandetanib-Eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies.

BACKGROUND: Transarterial chemoembolization (TACE) is the current standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) and is also a treatment option for patients with liver metastases from colorectal cancer. However, TACE is not a curative treatment, and tumor progression occurs in more than half of the patients treated. Despite advances and technical refinements of TACE, including the introduction of drug-eluting beads-TACE, the clinical efficacy of TACE has not been optimized, and improved arterial therapies are required. OBJECTIVE: The primary objectives of the VEROnA study are to evaluate the safety and tolerability of vandetanib-eluting radiopaque embolic beads (BTG-002814) in patients with resectable liver malignancies and to determine concentrations of vandetanib and the N-desmethyl metabolite in plasma and resected liver following treatment with BTG-002814. METHODS: The VEROnA study is a first-in-human, open-label, single-arm, phase 0, window-of-opportunity study of BTG-002814 (containing 100 mg vandetanib) delivered transarterially, 7 to 21 days before surgery in patients with resectable liver malignancies. Eligible patients have a diagnosis of colorectal liver metastases, or HCC (Childs Pugh A), diagnosed histologically or radiologically, and are candidates for liver surgery. All patients are followed up for 28 days following surgery. Secondary objectives of this study are to evaluate the anatomical distribution of BTG-002814 on noncontrast-enhanced imaging, to evaluate histopathological features in the surgical specimen, and to assess changes in blood flow on dynamic contrast-enhanced magnetic resonance imaging following treatment with BTG-002814. Exploratory objectives of this study are to study blood biomarkers with the potential to identify patients likely to respond to treatment and to correlate the distribution of BTG-002814 on imaging with pathology by 3-dimensional modeling. RESULTS: Enrollment for the study was completed in February 2019. Results of a planned interim analysis were reviewed by a safety committee after the first 3 patients completed follow-up. The recommendation of the committee was to continue the study without any changes to the dose or trial design, as there were no significant unexpected toxicities related to BTG-002814. CONCLUSIONS: The VEROnA study is studying the feasibility of administering BTG-002814 to optimize the use of this novel technology as liver-directed therapy for patients with primary and secondary liver cancer. TRIAL REGISTRATION: ClinicalTrial.gov NCT03291379; https://clinicaltrials.gov/ct2/show/NCT03291379. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13696.

Transarterial Chemoembolisation of Colorectal Liver Metastases with Irinotecan-Loaded Beads: A Bi-institutional Analysis of 125 Treatments in 53 Patients.

PURPOSE: To retrospectively review outcomes in patients treated for colorectal liver metastases with DEBIRI. MATERIALS AND METHODS: A retrospective analysis of patients with CRLM treated with DEBIRI was performed between 2008 and 2017 between two tertiary centres. Outcome parameters were overall survival and hepatic progression-free survival, as well as safety. Subgroup analyses were performed to assess the impact on outcomes of hepatic tumour burden at time of treatment, the presence of extrahepatic disease, prior systemic chemotherapy and the prior administration of systemic irinotecan-containing chemotherapy. RESULTS: Fifty-three patients received 125 treatments with DEBIRI over the study period. Median age of patients was 71 (range 41-88). Patients previously received a median of 1 line of chemotherapy (range 1-5). Median number of DEBIRI treatments was 2 (range 1-6). The median survival from first treatment was 14.5 months (range 1-107). Median hepatic progression-free survival was 5 months (0-86.5 months). The presence of extrahepatic disease (seen in 45% of patients) correlated with lower OS. Prolonged OS was seen in patients who received previous ablation and systemic chemotherapy. Technical success rate was found to be 99%. Post-procedural complication rate was 6%. CONCLUSION: Our findings add to the growing body of literature to support the safety profile of DEBIRI in the treatment of CRLM. Further studies will be necessary to help establish the optimum berth of DEBIRI in the treatment algorithm for colorectal liver metastases.

A novel technique for inferior vena cava filter extraction.

Inferior vena cava (IVC) filters are used to protect against pulmonary embolism in high-risk patients. Whilst the insertion of retrievable IVC filters is gaining popularity, a proportion of such devices cannot be removed using standard techniques. We describe a novel approach for IVC filter removal that involves snaring the filter superiorly along with the use of flexible forceps or laser devices to dissect the filter struts from the caval wall. This technique has used to successfully treat three patients without complications in whom standard techniques failed.

Pharmacomechanical thrombolysis in the management of paget-schroetter syndrome.

Paget-Schroetter syndrome (PSS) is a rare form of thoracic outlet syndrome caused by axillosubclavian vein thrombosis which typically presents in healthy young adults. Prompt therapy, traditionally by means of catheter-directed thrombolysis (CDT) prior to definitive surgery, can prevent the subsequent onset of postthrombotic syndrome (PTS) and considerable disability. As CDT is associated with major haemorrhage and high overall treatment cost, pharmacomechanical thrombectomy (PMT) seems to be an attractive alternative which combines pharmacological thrombolysis with mechanical clot disruption. The Trellis-8 peripheral infusion catheter is an example of such a treatment which provides topical thrombolysis in an isolated zone. We describe the use of the Trellis-8 PMT system in the successful management of three patients with PSS.

Techniques for removing bilateral renal artery stents prior to fenestrated endovascular aneurysm repair.

PURPOSE: To demonstrate 2 endovascular methods for successful intravascular stent extraction. TECHNIQUE: In preparation for fenestrated endovascular aneurysm repair, renal artery stents may be implanted for focal vessel stenosis at the ostium. In a recent case, bilateral renal artery stents were deployed with >50% protruding into the aortic lumen, thus rendering fenestrated endografting impossible. Two techniques were employed to extract the stents. In the left renal artery, the stent was extracted using an endovascular snare, but the right renal artery stent could not be removed with this method. Instead, an endoscopic forceps was advanced down a 16-F sheath, and the stent was grasped, extracted, and released into the aneurysm sac. The endovascular repair then proceeded in the usual fashion. CONCLUSION: The need to remove a stent prior to endovascular aneurysm repair is not a common problem encountered by most endovascular specialists; however, these methods should be in their armamentarium should the need arise.

Placement of a branched stent graft into the false lumen of a chronic type B aortic dissection.

The treatment of chronic type B aortic dissections remains challenging and controversial. Currently most centers advocate open or endovascular intervention for patients with evidence of malperfusion, rupture or impending rupture, continued pain, or aneurysm formation. Regardless of the type of intervention, the incidence of complications or death remains high, even when undertaken in an elective setting. The standard endovascular treatment usually involves placement of a stent graft into the true lumen of the dissection in an effort to exclude the false lumen. This case report describes the placement of a branched stent graft into the false lumen of a patient with chronic type B dissection to encourage exclusion and thrombosis of the true lumen whilst maintaining flow to all visceral vessels.