Ripal Gandhi, MD, FSIR, and Suvranu Ganguli, MD, FSIR Fall 2018
This column alerts SIR members to abstracts that may have an impact on their practice and how they converse with referring clinicians. If you would like to suggest abstracts you feel should be included, email us at email@example.com or firstname.lastname@example.org.
Efficacy of microwave ablation versus radiofrequency ablation for the treatment of hepatocellular carcinoma in patients with chronic liver disease: A randomised controlled phase 2 trial.
Lancet Gastroenterol Hepatol. 2018 May;3(5):317–325. doi: 10.1016/S2468–1253(18)30029-3. Epub 2018 Mar 2.
Vietti Violi N, Duran R, Guiu B, Cercueil JP, Aubé C, Digklia A, Pache I, Deltenre P, Knebel JF, Denys A.
BACKGROUND: Radiofrequency ablation is the recommended treatment for patients with hepatocellular carcinoma who have lesions smaller than 3 cm and are therefore not candidates for surgery. Microwave ablation is a more recent technique with certain theoretical advantages that have not yet been confirmed clinically. We aimed to compare the efficacy of both techniques in the treatment of hepatocellular carcinoma lesions of 4 cm or smaller.
METHODS: We did a randomised controlled, single-blinded phase 2 trial at four tertiary university centres in France and Switzerland. Patients with chronic liver disease and hepatocellular carcinoma with up to three lesions of 4 cm or smaller who were not eligible for surgery were randomised to receive microwave ablation (experimental group) or radiofrequency ablation (control group). Randomisation was centralised and done by use of a fixed block method (block size 4). Patients were randomly assigned by a co-investigator by use of the sealed opaque envelope method and were masked to the treatment; physicians were not masked to treatment, since the devices used were different. The primary outcome was the proportion of lesions with local tumour progression at 2 years of follow-up. Local tumour progression was defined as the appearance of a new nodule with features typical of hepatocellular carcinoma in the edge of the ablation zone. All analyses were done in the per-protocol population. The study is completed, but patients will continue to be followed up
for 5 years. This study is registered with clinicaltrials.gov, number NCT02859753.
FINDINGS: Between Nov. 15, 2011, and Feb. 27, 2015, 152 patients were randomly assigned: 76 patients to receive microwave ablation and 76 patients to receive radiofrequency ablation. For the per-protocol analysis, five patients were excluded from the microwave ablation group as were three patients from the radiofrequency ablation group. Median follow-up was 26 months (IQR 18–29) in the microwave ablation group and 25 months (18–34) in the radiofrequency ablation group. At 2 years, six (6 percent) of 98 lesions had local tumour progression in the microwave ablation group as did 12 (12 percent) of 104 in the radiofrequency ablation group (risk ratio 1.62, 95 percent CI, 0.66 to 3.94; p=0.27). Complications were infrequent, with only two grade 4 complications (two events of arterial bleeding requiring embolisation, both in the microwave ablation group) and three grade 3 complications (pneumothorax; lesion of the umbilical vein; and intrahepatic segmental necrosis, all in the radiofrequency ablation group). No treatment-related deaths were reported.
INTERPRETATION: Although we did not find that microwave ablation was more effective than radiofrequency ablation for treatment of hepatocellular carcinoma lesions of 4 cm or smaller, our results show that the proportion of lesions with local tumour progression at 2 years of follow-up was low with both tested percutaneous methods.
Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): A multicentre, international, single-blind, randomised, sham-controlled trial.
Lancet. 2018 Jun 9;391(10137):2335–2345. doi: 10.1016/S0140–6736(18)31082-1. Epub 2018 May 23.
Azizi M, Schmieder RE, Mahfoud F, Weber MA, Daemen J, Davies J, Basile J, Kirtane AJ, Wang Y, Lobo MD, Saxena M, Feyz L, Rader F, Lurz P, Sayer J, Sapoval M, Levy T, Sanghvi K, Abraham J, Sharp ASP, Fisher NDL, Bloch MJ, Reeve-Stoffer H, Coleman L, Mullin C, Mauri L; RADIANCE-HTN Investigators.
BACKGROUND: Early studies suggest that radiofrequency-based renal denervation reduces blood pressure in patients with moderate hypertension. We investigated whether an alternative technology using endovascular ultrasound renal denervation reduces ambulatory blood pressure in patients with hypertension in the absence of antihypertensive medications.
METHODS: RADIANCE-HTN SOLO was a multicentre, international, single-blind, randomised, sham-controlled trial done at 21 centres in the United States and 18 in Europe. Patients with combined systolic-diastolic hypertension aged 18–75 years were eligible if they had ambulatory blood pressure greater than or equal to 135/85 mm Hg and less than 170/105 mm Hg after a 4-week discontinuation of up to two antihypertensive medications and had suitable renal artery anatomy. Patients were randomised (1:1) to undergo renal denervation with the Paradise system (ReCor Medical, Palo Alto, Calif.) or a sham procedure consisting of renal angiography only. The randomisation sequence was computer generated and stratified by centres with randomised blocks of four or six and permutation of treatments within each block. Patients and outcome assessors were blinded to randomisation. The primary effectiveness endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Patients were to remain off antihypertensive medications throughout the 2 months of follow-up unless specified blood pressure criteria were exceeded. Major adverse events included all-cause mortality, renal failure, an embolic event with end-organ damage, renal artery or other major vascular complications requiring intervention, or admission to hospital for hypertensive crisis within 30 days and new renal artery stenosis within 6 months. This study is registered with clinicaltrials.gov, number NCT02649426.
FINDINGS: Between March 28, 2016, and Dec. 28, 2017, 803 patients were screened for eligibility and 146 were randomised to undergo renal denervation (n=74) or a sham procedure (n=72). The reduction in daytime ambulatory systolic blood pressure was greater with renal denervation (-8.5 mm Hg, SD 9.3) than with the sham procedure (-2.2 mm Hg, SD 10.0; baseline-adjusted difference between groups: -6.3 mm Hg, 95 percent CI, -9.4 to -3.1, p=0·0001). No major adverse events were reported in either group.
INTERPRETATION: Compared with a sham procedure, endovascular ultrasound renal denervation reduced ambulatory blood pressure at 2 months in patients with combined systolic-diastolic hypertension in the absence of medications.
A randomized trial of early endovenous ablation in venous ulceration.
N Engl J Med. 2018 May 31;378(22):2105–2114. doi: 10.1056/NEJMoa1801214. Epub 2018 Apr 24.
Gohel MS, Heatley F, Liu X, Bradbury A, Bulbulia R, Cullum N, Epstein DM, Nyamekye I, Poskitt KR, Renton S, Warwick J, Davies AH; EVRA Trial Investigators.
BACKGROUND: Venous disease is the most common cause of leg ulceration. Although compression therapy improves venous ulcer healing, it does not treat the underlying causes of venous hypertension. Treatment of superficial venous reflux has been shown to reduce the rate of ulcer recurrence, but the effect of early endovenous ablation of superficial venous reflux on ulcer healing remains unclear.
METHODS: In a trial conducted at 20 centers in the United Kingdom, we randomly assigned 450 patients with venous leg ulcers to receive compression therapy and undergo early endovenous ablation of superficial venous reflux within 2 weeks after randomization (early-intervention group) or to receive compression therapy alone, with consideration of endovenous ablation deferred until after the ulcer was healed or until 6 months after randomization if the ulcer was unhealed (deferred-intervention group). The primary outcome was the time to ulcer healing. Secondary outcomes were the rate of ulcer healing at 24 weeks, the rate of ulcer recurrence, the length of time free from ulcers (ulcer-free time) during the first year after randomization, and patient-reported health-related quality of life.
RESULTS: Patient and clinical characteristics at baseline were similar in the two treatment groups. The time to ulcer healing was shorter in the early-intervention group than in the deferred-intervention group; more patients had healed ulcers with early intervention (hazard ratio for ulcer healing, 1.38; 95 percent CI, 1.13 to 1.68; p=0.001). The median time to ulcer healing was 56 days (95 percent CI, 49 to 66) in the early-intervention group and 82 days (95 percent CI, 69 to 92) in the deferred-intervention group. The rate of ulcer healing at 24 weeks was 85.6 percent in the early-intervention group and 76.3 percent in the deferred-intervention group. The median ulcer-free time during the first year after trial enrollment was 306 days (interquartile range, 240 to 328) in the early-intervention group and 278 days (interquartile range, 175 to 324) in the deferred-intervention group (p=0.002). The most common procedural complications of endovenous ablation were pain and deep-vein thrombosis.
CONCLUSIONS: Early endovenous ablation of superficial venous reflux resulted in faster healing of venous leg ulcers and more time free from ulcers than deferred endovenous ablation. (Funded by the National Institute for Health Research Health Technology Assessment Program; EVRA Current Controlled Trials number, ISRCTN02335796.)
Tenecteplase versus alteplase before thrombectomy for ischemic stroke.
N Engl J Med. 2018 Apr 26;378(17):1573–1582. doi: 10.1056/NEJMoa1716405.
Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, Yan B, Bush SJ, Dewey HM, Thijs V, Scroop R, Simpson M, Brooks M, Asadi H, Wu TY, Shah DG, Wijeratne T, Ang T, Miteff F, Levi CR, Rodrigues E, Zhao H, Salvaris P, Garcia-Esperon C, Bailey P1, Rice H, de Villiers L, Brown H, Redmond K, Leggett D, Fink JN, Collecutt W, Wong AA, Muller C, Coulthard A, Mitchell K, Clouston J, Mahady K, Field D, Ma H, Phan TG, Chong W, Chandra RV, Slater LA, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Bladin CF, Sharma G, Desmond PM, Parsons MW, Donnan GA, Davis SM; EXTEND-IA TNK Investigators.
BACKGROUND: Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion.
METHODS: We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50 percent of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage.
RESULTS: Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22 percent of the patients treated with tenecteplase versus 10 percent of those treated with alteplase (incidence difference, 12 percentage points; 95 percent CI, 2 to 21; incidence ratio, 2.2; 95 percent CI, 1.1 to 4.4; p=0.002 for noninferiority; p=0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95 percent CI, 1.0 to 2.8; p=0.04). Symptomatic intracerebral hemorrhage occurred in 1 percent of the patients in each group.
CONCLUSIONS: Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset. (Funded by the National Health and Medical Research Council of Australia and others; EXTEND-IA TNK clinicaltrials.gov number, NCT02388061.)