Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial.

BACKGROUND: Urothelial carcinomas of the upper urinary tract (UTUCs) are rare, with poorer stage-for-stage prognosis than urothelial carcinomas of the urinary bladder. No international consensus exists on the benefit of adjuvant chemotherapy for patients with UTUCs after nephroureterectomy with curative intent. The POUT (Peri-Operative chemotherapy versus sUrveillance in upper Tract urothelial cancer) trial aimed to assess the efficacy of systemic platinum-based chemotherapy in patients with UTUCs. METHODS: We did a phase 3, open-label, randomised controlled trial at 71 hospitals in the UK. We recruited patients with UTUC after nephroureterectomy staged as either pT2-T4 pN0-N3 M0 or pTany N1-3 M0. We randomly allocated participants centrally (1:1) to either surveillance or four 21-day cycles of chemotherapy, using a minimisation algorithm with a random element. Chemotherapy was either cisplatin (70 mg/m2) or carboplatin (area under the curve [AUC]4·5/AUC5, for glomerular filtration rate <50 mL/min only) administered intravenously on day 1 and gemcitabine (1000 mg/m2) administered intravenously on days 1 and 8; chemotherapy was initiated within 90 days of surgery. Follow-up included standard cystoscopic, radiological, and clinical assessments. The primary endpoint was disease-free survival analysed by intention to treat with a Peto-Haybittle stopping rule for (in)efficacy. The trial is registered with ClinicalTrials.gov, NCT01993979. A preplanned interim analysis met the efficacy criterion for early closure after recruitment of 261 participants. FINDINGS: Between June 19, 2012, and Nov 8, 2017, we enrolled 261 participants from 57 of 71 open study sites. 132 patients were assigned chemotherapy and 129 surveillance. One participant allocated chemotherapy withdrew consent for data use after randomisation and was excluded from analyses. Adjuvant chemotherapy significantly improved disease-free survival (hazard ratio 0·45, 95% CI 0·30-0·68; p=0·0001) at a median follow-up of 30·3 months (IQR 18·0-47·5). 3-year event-free estimates were 71% (95% CI 61-78) and 46% (36-56) for chemotherapy and surveillance, respectively. 55 (44%) of 126 participants who started chemotherapy had acute grade 3 or worse treatment-emergent adverse events, which accorded with frequently reported events for the chemotherapy regimen. Five (4%) of 129 patients managed by surveillance had acute grade 3 or worse emergent adverse events. No treatment-related deaths were reported. INTERPRETATION: Gemcitabine-platinum combination chemotherapy initiated within 90 days after nephroureterectomy significantly improved disease-free survival in patients with locally advanced UTUC. Adjuvant platinum-based chemotherapy should be considered a new standard of care after nephroureterectomy for this patient population. FUNDING: Cancer Research UK.

Progressive Device Failure at Long Term Follow Up of the Nellix EndoVascular Aneurysm Sealing (EVAS) System.

OBJECTIVE: High rates of midterm failure of the Nellix EndoVascular Aneurysm Sealing (EVAS) System resulted in device withdrawal from the UK market. The study aim was to report long term Nellix EVAS outcomes and management of a failing device. METHODS: A retrospective review of EVAS procedures at a tertiary unit was performed. Device failure was defined as a triad of stent migration, stent separation, and secondary sac expansion, or any intervention for type 1 endoleak, device rupture, or explant. RESULTS: 161 (male n = 140, female n = 21) patients with a median follow up of 6.0 (IQR 5.0-6.6) years were included. Freedom from all cause mortality estimate at six years was 41.5%. There were 70 (43.5%) device failures with a freedom from device failure estimate at six years of 32.3%. Failure was the result of sac expansion (n = 41), caudal stent migration (n = 36), stent separation (n = 26), and secondary AAA rupture (n = 15). A substantial number of type 1 endoleaks was present (1a n = 33, 1b n = 11), but the type 2 endoleak rate was low at 3.7%. Some 36 (22.4%) patients required re-intervention. Twenty-one patients underwent explant with no 30 day deaths. Six patients underwent Nellix-in-Nellix application (NINA) with one early death from bowel ischaemia and one patient who died later from non-aneurysm related cause. Two NINA patients have ongoing sac expansion and two have had thrombosis of a Nellix limb or visceral stent. Proximal embolisation was only successful in one of six cases. CONCLUSION: The long term failure rate of Nellix EVAS is high. All patients with a device must be informed and be enrolled in enhanced surveillance. EVAS explant is an acceptable technique with favourable outcomes. Management by open explant, if the patient is fit, should be considered early and offered to those with device failure.

Editor's Choice - Mid-term Migration and Device Failure Following Endovascular Aneurysm Sealing with the Nellix Stent Graft System - a Single Centre Experience.

OBJECTIVE: Endovascular aneurysm sealing (EVAS) with the Nellix stent graft system is a novel concept in the management of abdominal aortic aneurysm (AAA) that aims to reduce the prevalence of all endoleaks following endovascular repair. There are few data describing the longer-term durability of this approach. The aim was to report the longer-term outcomes following EVAS in a single centre. METHODS: This is a retrospective review of all patients that underwent Nellix at Cambridge University Hospitals Foundation Trust. Factors that are described as device failure include secondary sac rupture, graft explantation, further surgical procedures for Type 1 endoleak, or major migration of the stent grafts with pressurisation of the aortic sac. RESULTS: A total of 161 patients have been treated with Nellix. The indications included primary AAA (n = 115), ruptured AAA (n = 4), salvage of other aortic grafts (n = 18), primary iliac aneurysm (n = 6), and chimney EVAS (ChEVAS) for pararenal AAA (n = 18). In total there have been 42 graft failures in patients treated with EVAS for primary AAA. The 4 year freedom from graft failure was 42% in patients treated for primary AAA. Failures mostly occurred more than 2 years post-Nellix implant. There were eight secondary sac ruptures (incidence 2.4 per 100 person years) and there have been 14 graft explants. CONCLUSIONS: Failure of aneurysm sealing following treatment with Nellix has been more common than anticipated and can cause aortic rupture. Post-operative surveillance of Nellix stent grafts is crucial to identify features of failure.

Morphometric Assessment as a Predictor of Outcome in Older Vascular Surgery Patients.

BACKGROUND: Frailty is a recognized predictor of poor outcome in patients undergoing surgical intervention. Frailty is intricately linked with body morphology, which can be evaluated using morphometric assessment via computerized tomographic (CT) imaging. We aimed to assess the predictive power of such objective assessments in a broad cohort of vascular surgical patients. METHODS: A consecutive series of patients aged over 65 years admitted to a vascular unit, who had undergone CT imaging of the abdomen, were analyzed. Demographic and patient-specific data were collated alongside admission relevant information. Outcomes included mortality, length of stay, health care-related costs, and discharge destination. Images were analyzed for 4 morphometric measurements: (1) psoas muscle area, (2) mean psoas density, (3) subcutaneous fat depth, and (4) intra-abdominal fat depth, all taken at the level of the fourth lumbar vertebra. RESULTS: Two hundred and ten patients were initially analyzed. Forty-four patients had significant retroperitoneal and abdominal abnormalities that limited appropriate CT analysis. Decreased subcutaneous fat depth was significantly associated with mortality, readmission within 12 months, and increased cost of health care (P < 0.01, adjusted for confounders). Psoas muscle area was significantly associated with readmission-free survival. CONCLUSIONS: Morphometric analysis predicts poorer outcome in a broad cohort of vascular surgery patients. Such assessment is likely to enhance patient counseling regarding individual risk as well as enhancing the ability to undertake risk-modified surgical audit.

Gadofosveset-enhanced thoracic MR venography: a comparative study evaluating steady state imaging versus conventional first-pass time-resolved dynamic imaging.

Background Dedicated blood-pool contrast agents combined with optimal angiographic protocols could improve the diagnostic accuracy of thoracic magnetic resonance angiography (MRA). Purpose To assess the clinical utility of Gadofesveset-enhanced imaging and compare an optimized steady-state (SS) sequence against conventional first-pass dynamic multi-phase (DMP) imaging. Material and Methods Twenty-nine patients (17 men, 12 women; mean age = 42.7, age range = 18-72 years) referred for MR thoracic venography were recruited. Imaging was performed on a 1.5T MRI system. A blood-pool contrast agent (Gadofesveset) was administered intravenously. Thirty temporal phases were acquired using DMP. This was immediately followed by a high-resolution SS sequence. Three radiologists in consensus reviewed seven thoracic vascular segments after randomizing the acquisition order. Image quality, stenoses, thromboses, and artifacts were graded using a categorical scoring system. The image quality for both approaches was compared using Wilcoxon's signed-rank test. McNemar's test was used to compare the proportions of stenosis grades, thrombus and artifacts. Results SS had significantly better image quality than DMP (3.14 ± 0.73 and 2.92 ± 0.60, respectively; P < 0.001). SS identified fewer stenoses (>50%) than DMP; the differences in stenosis categorizations was statistically significant ( P = 0.013). There was no significant difference in the proportions of vessels with thromboses ( P = 0.617). DMP produced more artifacts than SS (101 versus 85); however, the difference was not statistically significant ( P = 0.073). Conclusion Gadofesveset-enhanced thoracic angiography is clinically feasible. SS imaging produces better image quality and fewer artifacts than conventional DMP imaging.

Evaluation of velocity-sensitized and acceleration-sensitized NCE-MRA for below-knee peripheral arterial disease.

PURPOSE: To evaluate the diagnostic performance of velocity- and acceleration-sensitized noncontrast-enhanced magnetic resonance angiography (NCE-MRA) of the infrageniculate arteries using contrast-enhanced MRA (CE-MRA) as a reference standard. MATERIALS AND METHODS: Twenty-four patients with symptoms of peripheral arterial disease were recruited. Each patient's infrageniculate arterial tree was examined using a velocity-dependent flow-sensitized dephasing (VEL-FSD) technique, an acceleration-dependent (ACC-FSD) technique, and our conventional CE-MRA technique performed at 1.5T. The images were independently reviewed by two experienced vascular radiologists, who evaluated each vessel segment to assess visibility, diagnostic confidence, venous contamination, and detection of pathology. RESULTS: In all, 432 segments were evaluated by each of the three techniques by each reader in total. Overall diagnostic confidence was rated as moderate or high in 98.5% of segments with CE-MRA, 92.1% with VEL-FSD, and 79.9% with ACC-FSD. No venous contamination was seen in 96% of segments with CE-MRA, 72.2% with VEL-FSD, and 85.8% with ACC-FSD. Per-segment, per-limb, and per-patient sensitivities for detecting significant stenotic disease were 63.4%, 73%, and 92%, respectively, for ACC-FSD, and 65.3%, 87.2%, and 96% for VEL-FSD, and as such no significant statistical change was detected using McNemar's chi-squared test with P-values of 1.00, 0.13, and 0.77 obtained, respectively. CONCLUSION: Flow-dependent NCE-MRA techniques may have a role to play in evaluation of patients with peripheral vascular disease. Increased sensitivity of a velocity-based technique compared to an acceleration-based technique comes at the expense of greater venous contamination. LEVEL OF EVIDENCE: 2J. Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;45:1846-1853.

Imaging After Nellix Endovascular Aneurysm Sealing: A Consensus Document.

Endovascular aneurysm sealing (EVAS) using the Nellix system is a new and different method of abdominal aortic aneurysm repair. Normal postoperative imaging has unique appearances that change with time; complications also have different and specific appearances. This consensus document on the imaging findings after Nellix EVAS is based on the collective experience of the sites involved in the Nellix EVAS Global Forward Registry and the US Investigational Device Exemption Trial. The normal findings on computed tomography (CT), duplex ultrasound, magnetic resonance imaging, and plain radiography are described. With time, endobag appearances change on CT due to contrast migration to the margins of the hydrogel polymer within the endobag. Air within the endobag also has unique appearances that change over time. Among the complications after Nellix EVAS, type I endoleak usually presents as a curvilinear area of flow between the endobag and aortic wall, while type II endoleak is typically small and usually occurs where an aortic branch artery lies adjacent to an irregular aortic blood lumen that is not completely filled by the endobag. Procedural aortic injury is an uncommon but important complication that occurs as a result of overfilling of the endobags during Nellix EVAS. The optimum imaging surveillance algorithm after Nellix EVAS has yet to be defined but is largely CT-based, especially in the first year postprocedure. However, duplex ultrasound also appears to be a sensitive modality in identifying normal appearances and complications.

Radiological Evaluation of Abdominal Endovascular Aortic Aneurysm Repair.

Endovascular aortic aneurysm repair (EVAR) is an alternative to open surgical repair of aortic aneurysms offering lower perioperative mortality and morbidity. As experience increases, clinicians are undertaking complex repairs with hostile aortic anatomy using branched or fenestrated devices or extra components such as chimneys to ensure perfusion to visceral branch vessels whilst excluding the aneurysm. Defining the success of EVAR depends on both clinical and radiographic criteria, but ultimately depends on complete exclusion of the aneurysm from the circulation. Aortic stent grafts are monitored using a combination of imaging modalities including computed tomography angiography (CTA), ultrasonography, magnetic resonance imaging, plain films, and nuclear medicine studies. This article describes when and how to evaluate aortic stent grafts using each of these modalities along with the characteristic features of several of the main stent grafts currently used in clinical practice. The commonly encountered complications from EVAR are also discussed and how they can be detected using each imaging modality. As the radiation burden from serial follow up CTA imaging is now becoming a concern, different follow-up imaging strategies are proposed depending on the complexity of the repair and based on the relative merits and disadvantages of each imaging modality.

Measuring stone volume - three-dimensional software reconstruction or an ellipsoid algebra formula?

OBJECTIVES: To determine the optimal method for assessing stone volume, and thus stone burden, by comparing the accuracy of scalene, oblate, and prolate ellipsoid volume equations with three-dimensional (3D)-reconstructed stone volume. Kidney stone volume may be helpful in predicting treatment outcome for renal stones. While the precise measurement of stone volume by 3D reconstruction can be accomplished using modern computer tomography (CT) scanning software, this technique is not available in all hospitals or with routine acute colic scanning protocols. Therefore, maximum diameters as measured by either X-ray or CT are used in the calculation of stone volume based on a scalene ellipsoid formula, as recommended by the European Association of Urology. METHODS: In all, 100 stones with both X-ray and CT (1-2-mm slices) were reviewed. Complete and partial staghorn stones were excluded. Stone volume was calculated using software designed to measure tissue density of a certain range within a specified region of interest. Correlation coefficients among all measured outcomes were compared. Stone volumes were analysed to determine the average 'shape' of the stones. RESULTS: The maximum stone diameter on X-ray was 3-25 mm and on CT was 3-36 mm, with a reasonable correlation (r = 0.77). Smaller stones (<9 mm) trended towards prolate ellipsoids ('rugby-ball' shaped), stones of 9-15 mm towards oblate ellipsoids (disc shaped), and stones >15 mm towards scalene ellipsoids. There was no difference in stone shape by location within the kidney. CONCLUSIONS: As the average shape of renal stones changes with diameter, no single equation for estimating stone volume can be recommended. As the maximum diameter increases, calculated stone volume becomes less accurate, suggesting that larger stones have more asymmetric shapes. We recommend that research looking at stone clearance rates should use 3D-reconstructed stone volumes when available, followed by prolate, oblate, or scalene ellipsoid formulas depending on the maximum stone diameter.

Initial clinical evaluation of a non-contrast-enhanced MR angiography method in the distal lower extremities.

PURPOSE: To report the initial experience and diagnostic performance applying a novel flow-dependent non-contrast-enhanced MR angiography (NCE-MRA) method, in patients with suspected peripheral vascular disease, in comparison with established contrast-enhanced MRA (CE-MRA). METHODS: The lower legs of 34 patients were imaged at 1.5 T with both NCE-MRA and CE-MRA. The NCE-MRA method consisted of a cardiac-gated balanced-SSFP sequence with controllable flow-suppression preparation. Flow-suppressed and unsuppressed datasets were subtracted to obtain angiograms. Two experienced radiologists assessed both NCE-MRA and CE-MRA images, first independently and then in consensus to resolve significant disagreements. Signal loss, vessel conspicuity, vascular disease, venous contamination, artifacts, and diagnostic confidence were assessed. RESULTS: Using the CE-MRA as the "gold standard," the per-segment sensitivity and specificity for detection of significant disease were 81.7% and 90.9%, respectively. Mean diagnostic confidence (scale 0-4) was 3.4 for NCE-MRA and 3.9 for CE-MRA. Most vessel segments were well visualized but the popliteal arteries often suffered some technique-related signal loss. CONCLUSIONS: The NCE-MRA method was able to visualize most vessel segments with good or excellent confidence, few artifacts, and excellent background suppression, giving moderate agreement with CE-MRA. However, some segments were poorly visualized, probably due to flow profile distortion in these patients.

Retroperitoneal aortic hemorrhage caused by penetration of an endovascular stent-graft anchoring barb.

PURPOSE: To report a rare case of acute intraoperative retroperitoneal hemorrhage secondary to aortic penetration by the suprarenal anchoring barb on a stent-graft. CASE REPORT: A 75-year-old patient on dual antiplatelet therapy for coronary stents and low-molecular-weight heparin for atrial thrombus underwent elective endovascular repair of a 6.7-cm infrarenal abdominal aortic aneurysm. A device with suprarenal fixation and metal anchoring barbs was implanted, and a molding balloon was used that at no time covered the proximal bare metal stents or barbs. In recovery, the patient became tachycardic and hypotensive. After resuscitation, imaging identified an anterior barb penetrating the aortic wall, causing the acute retroperitoneal hemorrhage. A decision to treat conservatively rather than resort to open surgery was difficult but ultimately influenced by the patients' high risk for open surgery. The patient was treated by aggressive reversal of heparin and platelet transfusion, and the bleed settled spontaneously. CONCLUSION: Major surgery and subsequent morbidity may be avoided by medical management of what would appear to be a surgical problem.

Endovascular Abdominal Aortic Aneurysm Repair: Overview of Current Guidance, Strategies, and New Technologies, Perspectives from the United Kingdom.

Endovascular aortic aneurysm repair has changed the management of patients affected by this condition, offering a minimally invasive solution with satisfactory outcomes. Constant evolution of this technology has expanded the use of endovascular devices to more complex cases. The purpose of this review article is to describe the current strategies, guidance, and technologies in this field, with a particular focus on practices in the United Kingdom.

Images of the month 2: Pulmonary artery pseudoaneurysm formation within uterine leiomyosarcoma metastases.

We present a rare case of pulmonary artery pseudoaneurysm formation in leiomyosarcoma metastases with evidence of acute bleeding and subsequent interventional radiological management.

Use of heparin coated vascular stents in femoropopliteal chronic total occlusions: Long term outcomes.

PURPOSE: To evaluate the long-term clinical efficacy of the Tigris © stent (Gore ©) in femoropopliteal chronic total occlusions (CTOs). MATERIAL AND METHODS: This single centre retrospective study included 29 patients treated with 47 Tigris© stents for CTOs. Lesion location, type, length, revascularisation method, smoking status and diabetes were reviewed. Clinical follow-up was performed. Primary safety points were complications and adverse events. Secondary efficacy points were symptom deterioration, freedom from target lesion revascularization (TLR) and amputation rate. Freedom from TLR was evaluated with Kaplan-Meier analysis; Cox multivariable logistic regression analysis of the factors associated with stent re-occlusion was also performed. RESULTS: All procedures were technically successful without any peri- or post-procedural complications and adverse events. Median follow-up was 48 months (range: 7-70). Lesions were located in the superficial femoral (19), popliteal (3) and femoropopliteal (7) arteries with mean lesion length 13.9 ±â€¯7.6 cm. In 12 patients subintimal recanalization was performed. Freedom from TLR rates at 6, 12, 18, 24 and 36 months were 96.6 %, 85.7 %, 81.9 %, 78.2 % and 74.3 % respectively. No stent fracture was observed and no amputation was performed in any of the patients. Smoking status, the presence of diabetes, lesion localization and recanalization type were not associated with stent re-occlusion. CONCLUSION: This study demonstrated that use of a heparin coated vascular stent for femoropopliteal CTOs appears to offer satisfactory long-term results.

Percutaneous Cystolitholapaxy Using the LithoClast Trilogy for Multiple Bladder Stones.

Background: Multiple large bladder calculi are traditionally managed through open cystolithotomy or transurethrally in patients who have an open bladder neck. Open procedures are technically challenging in patients who may have had multiple previous open surgeries, and may be associated with significant morbidity in patients with a high comorbid burden. Therefore, a percutaneous approach to such stones has been used especially when there is a closed bladder neck, and has been shown to be effective. There are a number of available devices for breaking stones in these approaches, the newest of which is the LithoClast Trilogy™ (EMS, Nyon, Switzerland) device, a probe that provides ultrasonic and mechanical calculi fragmentation and suction in a single instrument. Case Presentation: We describe the first reported case of percutaneous cystolitholapaxy using the LithoClast Trilogy device in a 41-year-old woman with spina bifida, and multiple large bladder calculi with a history of ileocystoplasty and Mitrofanoff formation, and a bladder neck closure for neuropathic bladder. The calculi measured 31 and 25 mm, and had a volume of 19.6 and 7.9 cm3 and average HU of 408 and 462, respectively. The calculi were composed of 37% calcium phosphate and 63% magnesium ammonium phosphate. Conclusion: We demonstrate that this approach can be used as a viable alternative to open surgery, which is of particular importance for complex patients who have undergone multiple previous open operations, and who may have a high comorbid burden.

Management and clinical outcome of concomitant pulmonary embolism and paradoxical saddle aortic arch embolism.

A 65-year-old man presented in a peri-arrest situation after collapse, he was found hypoxic with ischaemic arms. CT imaging showed massive bilateral pulmonary embolisms (PEs) and an aortic arch embolus extending from brachiocephalic trunk to left subclavian artery. Following intravenous thrombolysis, repeat imaging revealed that the aortic embolus had migrated distally into both axillary arteries and had occluded the right carotid from origin to skull base. Bilateral upper limb embolectomies were carried out from the brachial arteries together with forearm fasciotomies. Left hemianopia related to a right middle cerebral artery territory infarct was managed conservatively; forearm fasciotomy wounds were primarily closed and the patient was discharged on lifelong anticoagulation. A transoesophageal echocardiogram revealed a patent foramen ovale. This case demonstrates a very unusual presentation of concomitant PE and paradoxical saddle aortic arch embolism. A multidisciplinary approach has resulted in an excellent clinical outcome for this complex patient.

Life and bladder cancer: protocol for a longitudinal and cross-sectional patient-reported outcomes study of Yorkshire (UK) patients.

INTRODUCTION: Little is known about the impact of bladder cancer (BC) and its treatments on health-related quality of life (HRQL). To date, most work has been small in scale or restricted to subsets of patients. Life and bladder cancer is a cross-sectional and longitudinal study collecting patient-reported outcomes within two distinct cohorts. METHODS AND ANALYSIS: A longitudinal study will collect patient-reported outcomes at 3-monthly intervals from newly diagnosed patients. Eligible cases will be identified by recruiting hospitals and surveyed at baseline, 6, 9 and 12 months postdiagnosis to explore changes in outcomes over time. A separate cross-sectional cohort of patients diagnosed within the last 10 years across Yorkshire will be identified through cancer registration systems and surveyed once to explore longer-term HRQL in BC survivors. A comprehensive patient-reported outcome measure (PROM) has been developed using generic, cancer-specific and BC-specific instruments. The study will provide evidence about how useful these PROMs are in measuring BC patient HRQL. The outcome data will be linked with administrative health data (eg, treatment information from hospital data). ETHICS AND DISSEMINATION: The study has received the following approvals: Yorkshire and the Humber-South Yorkshire Research Ethics Committee (17/YH/0095), Health Research Authority Confidentiality Advisory Group (17/CAG/0054). Results will be made available to patients, funders, NHS Trusts, Clinical Commissioning Groups, Strategic Clinical Networks and other researchers.

Branched Thoraco-Abdominal Aortic Aneurysm Repair with Branch Access Through a Transapical Left Ventricular Approach.

Branched thoracic aortic aneurysm repair requires arterial access from above the diaphragm in order to insert the visceral branches. This is routinely performed from the subclavian, axillary or carotid arteries and less commonly direct thoracic aorta puncture. The left ventricular apex is an alternative access route which is commonly used for percutaneous aortic valve replacement and rarely used for EVAR, FEVAR and TEVAR access. Here we describe two patients for which the left ventricular apex was the most suitable available access to the visceral branches during a branched thoracic aortic aneurysm repair. This access should be considered as an alternative approach if conventional arterial access is not available.