Efficacy of high-intensity focused ultrasound-assisted hepatic resection (HIFU-AR) on blood loss reduction in patients with liver metastases requiring hepatectomy: study protocol for a randomized controlled trial

Abstract

BackgroundLiver resection is the only potentially curative treatment for colorectal liver metastases (LM). It is considered a safe procedure, but is often associated with blood loss during liver transection. Blood transfusions are frequently needed, but they are associated with increased morbidity and risk of recurrence. Many surgical devices have been developed to decrease blood loss. However, none of them has proven superior to the standard crushing technique. We developed a new, powerful intra-operative high-intensity focused ultrasound (HIFU) transducer which destroys tissue by coagulative necrosis. We aim to evaluate whether HIFU-assisted liver resection (HIFU-AR) results in reduced blood loss.MethodsThis is a prospective, single-centre, randomized (1:1 ratio), comparative, open-label phase II study. Patients with LM requiring a hepatectomy for ≥ 2 segments will be included. Patients with cirrhosis or sinusoidal obstruction syndrome with portal hypertension will be excluded. The primary endpoint is normalized blood loss in millilitres per square centimetre of liver section plane. Secondary endpoints are: total blood loss, transection time, transection time per square centimetre of liver area, haemostasis time, clip density on the liver section area, rate and duration of the Pringle manœuvre, rate of patients needing a blood transfusion, length of hospital stay, morbidity, patients with positive resection margin, and local recurrence. Assuming a blood loss of 7.6 ± 3.7 mL/cm2 among controls, the study will have 85% power to detect a twofold decrease of blood loss in the experimental arm, using a Wilcoxon (Mann-Whitney) rank-sum test with a 0.05 two-sided significance level. Twenty-one randomized patients per arm are required. Considering the risk of contraindications at surgery, up to eight patients may be enrolled in addition to the 42 planned, with an enrolment period of 24 months. Randomization will be stratified by surgeon.DiscussionWe previously demonstrated the safety and efficacy of intra-operative HIFU in patients operated on for LM. We also demonstrated the efficacy of HIFU-AR in a preclinical study. Participants in the HIFU-AR group of this randomized trial can expect to benefit from reduced blood loss and decreased ischemia of liver parenchyma.Trial registrationClinicaltrial.gov, NCT02728167. Registered on 22 March 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-1801-2) contains supplementary material, which is available to authorized users.

ALBI and P-ALBI grade in Child-Pugh A patients treated with drug eluting embolic chemoembolization for hepatocellular carcinoma

“…Most reports on clinical use of HIFU in liver tumor treatment are from China where USgHIFU has been used for HCC treatment, with reports of adequate feasibility, safety, and treatment outcomes (121)(122)(123)(124). In Europe, a current study examines the role of HIFU in reducing blood loss during liver resection (125). Only one single case of clinical treatment in liver tumors is reported from Europe (Rome) using MRgHIFU (126), and MRgHIFU is not in clinical use in treatment of liver tumors yet.…”

Systematic review and meta-analysis of the efficacy and safety of high-intensity focused ultrasound combined with transarterial chemoembolization and transarterial chemoembolization alone in the treatment of liver cancer

“…There was no obvious difference in the 6-month (OR =9.03, 95% CI: 0.87, 94.13, P=0.07) or 3-year (OR =2.26, 95% CI: 0.46, 11.21, P=0.32) SRs of patients between the 2 groups (P>0.05). The included articles showed homogeneity in the SRs of patients at 1 year, 2 years, and 5 years after surgery (I 2 <50%; Figures 5,6,8), so a fixed-effect model (FEM) was adopted. The SRs of patients in the experimental group at 1 year (OR =3.13, 95% CI: 1.92, 5.11, P<0.00001), 2 years (OR =3.38, 95% CI: 1.71, 6.66, P=0.0004), and 5 years (OR =2.15, 95% CI: 1.02, 4.55, P=0.04) after surgery were observably better than those of patients in the control group, and the differences were statistically significant (P<0.05).…”

“…In recent years, high-intensity focused ultrasound (HIFU) has been used as a tumor treatment method. Ultrasound can be used to achieve precise localization of the tumor lesions and deliver subsequent thermal tumor ablation therapy ( 8 , 9 ).…”

Recent Understanding of Colorectal Cancer Treatment

“…Results have been reported using the device for ablating tissue near tumors in segments prior to surgical resection, to assess accuracy and safety. Applications include reduction of hemorrhaging during surgery and potentially bridging more patients for surgical resection [190][191][192][193]. The device was shown capable of in vivo hepatic vessel occlusion for diameters of 2 mm [194], and studies have reported diameters of left hepatic arteries and right hepatic veins between 3 and 4 mm [195].…”