Definitive locoregional therapy (LRT) versus bridging LRT and liver transplantation with wait-and-not-treat approach for very early stage hepatocellular carcinoma

PURPOSE:Since the change in the United Network for Organ Sharing (UNOS) policy excluding patients with very early stage hepatocellular carcinoma (veHCC, single tumor nodule <2 cm) from receiving Model for End-stage Liver Disease (MELD) exception points, patients eligible to receive liver transplantation (LT) who fall in this category are commonly treated with locoregional therapy (LRT) after progression to UNOS T2 stage (1 nodule of 2–5 cm or up to 3 nodules, none above 3 cm). The aim of the current study is to compare the outcomes of patients treated with bridging LRT and LT with wait-and-not-treat approach with patients treated with definitive LRT.METHODS:A retrospective study has been performed on patients with veHCC evaluated in multidisciplinary liver tumor clinic of a large academic center between 2004–2011. Patients eligible for LT were assigned to the wait-and-not-treat group while patients who were not eligible were assigned to the definitive LRT group. Tumor size, time to treatment, severity of liver disease, recurrence and survival from time of detection were reviewed and recorded.RESULTS:A total of 19 patients were identified and treated with definitive LRT while 57 patients were treated with bridging LRT prior to LT after disease progression to T2 stage. Patients in the definitive LRT group were older (70.4±10.2 years vs. 58.7±5.9 years, P < 0.001) and had more comorbid conditions compared with the wait-and-not-treat group. Mean survival for definitive LRT group at the end of 5 years was 34.3±6.0 months with a median of 30.3 months (95% CI, 5.7–55.0 months) compared with 48.7±2.6 months for the wait-and-not-treat group, respectively (median not reached). The 3- and 5-year survival rates were 53.3% and 33.3% for the definitive LRT group compared with 78.9% and 68.4% for the patients in the wait-and-not-treat group. Survival rate at the end of 5 years was significantly better for the wait-and-not-treat group (P = 0.013).CONCLUSION:Based on the findings of current retrospective study, treating veHCC (UNOS T1 stage) patients listed for LT with bridging LRT after disease progression to T2 stage appears to be safe and effective with high 5-year survival rates

90Y Radioembolization for Hepatic Malignancy in Patients with Previous Biliary Intervention: Multicenter Analysis of Hepatobiliary Infections

PurposeTo determine the frequency of hepatobiliary infections after transarterial radioembolization (TARE) with yttrium 90 (90Y) in patients with liver malignancy and a history of biliary intervention.Materials and MethodsFor this retrospective study, records of all consecutive patients with liver malignancy and history of biliary intervention treated with TARE at 14 centers between 2005 and 2015 were reviewed. Data regarding liver function, 90Y dosimetry, antibiotic prophylaxis, and bowel preparation prophylaxis were collected. Primary outcome was development of hepatobiliary infection.ResultsOne hundred twenty-six patients (84 men, 42 women; mean age, 68.8 years) with primary (n = 39) or metastatic (n = 87) liver malignancy and history of biliary intervention underwent 180 procedures with glass (92 procedures) or resin (88 procedures) microspheres. Hepatobiliary infections (liver abscesses in nine patients, cholangitis in five patients) developed in 10 of the 126 patients (7.9%) after 11 of the 180 procedures (6.1%; nine of those procedures were performed with glass microspheres). All patients required hospitalization (median stay, 12 days; range, 2–113 days). Ten patients required percutaneous abscess drainage, three patients underwent endoscopic stent placement and stone removal, and one patient needed insertion of percutaneous biliary drains. Infections resolved in five patients, four patients died (two from infection and two from cancer progression while infection was being treated), and one patient continued to receive suppressive antibiotics. Use of glass microspheres (P = .02), previous liver resection or ablation (P = .02), and younger age (P = .003) were independently predictive of higher infection risk.ConclusionInfectious complications such as liver abscess and cholangitis are uncommon but serious complications of transarterial radioembolization with 90Y in patients with liver malignancy and a history of biliary intervention.© RSNA, 2018Online supplemental material is available for this article

Comparative Analysis of Cervical Spine Management in a Subset of Severe Traumatic Brain Injury Cases Using Computer Simulation

BACKGROUND: No randomized control trial to date has studied the use of cervical spine management strategies in cases of severe traumatic brain injury (TBI) at risk for cervical spine instability solely due to damaged ligaments. A computer algorithm is used to decide between four cervical spine management strategies. A model assumption is that the emergency room evaluation shows no spinal deficit and a computerized tomogram of the cervical spine excludes the possibility of fracture of cervical vertebrae. The study's goal is to determine cervical spine management strategies that maximize brain injury functional survival while minimizing quadriplegia. METHODS/FINDINGS: The severity of TBI is categorized as unstable, high risk and stable based on intracranial hypertension, hypoxemia, hypotension, early ventilator associated pneumonia, admission Glasgow Coma Scale (GCS) and age. Complications resulting from cervical spine management are simulated using three decision trees. Each case starts with an amount of primary and secondary brain injury and ends as a functional survivor, severely brain injured, quadriplegic or dead. Cervical spine instability is studied with one-way and two-way sensitivity analyses providing rankings of cervical spine management strategies for probabilities of management complications based on QALYs. Early collar removal received more QALYs than the alternative strategies in most arrangements of these comparisons. A limitation of the model is the absence of testing against an independent data set. CONCLUSIONS: When clinical logic and components of cervical spine management are systematically altered, changes that improve health outcomes are identified. In the absence of controlled clinical studies, the results of this comparative computer assessment show that early collar removal is preferred over a wide range of realistic inputs for this subset of traumatic brain injury. Future research is needed on identifying factors in projecting awakening from coma and the role of delirium in these cases

Randomized Embolization Trial for NeuroEndocrine Tumor Metastases to the Liver (RETNET): study protocol for a randomized controlled trial

Abstract Background Neuroendocrine tumors (NETs) are the second most common gastrointestinal malignancy after colon cancer. Up to 90% of patients with NETs develop liver metastases, which are a major determinant of symptoms and survival. Current guidelines recommend embolotherapy for progressive or symptomatic NET liver metastases, but the optimal technique among bland embolization, lipiodol chemoembolization, and drug-eluting bead chemoembolization remains unknown and controversial. Methods/design A prospective, open-label, multicenter randomized controlled trial will be conducted in patients with progressive or symptomatic unresectable NET liver metastases. Patients will be randomized to treatment with bland embolization, lipiodol chemoembolization, or drug-eluting microsphere chemoembolization, with 60 enrollees per arm. The primary endpoint will be hepatic progression-free survival (HPFS) following initial embolotherapy by RECIST criteria. The sample size is powered to detect an HR of 1.78 for HPFS following chemoembolization compared with bland embolization, which was estimated on the basis of existing retrospective studies. Secondary endpoints include overall progression-free survival, duration of symptom control, quality of life, rate of adverse events, and interval between embolotherapy cycles. Interim safety analyses will be performed at 10 and 30 patients per arm. Discussion The RETNET trial is a prospective, multicenter randomized controlled trial designed to determine the optimal embolotherapy technique for NET liver metastases. Trial registration ClinicalTrials.gov, NCT02724540. Registered on March 31, 2016

Lipiodol transarterial chemoembolization for hepatocellular carcinoma: A systematic review of efficacy and safety data

Transarterial chemoembolization (TACE) using lipiodol-based regimens, including the administration of an anticancer-in-oil emulsion followed by embolic agents, is widely used in the treatment of hepatocellular carcinoma (HCC). This approach has been supported by meta-analyses of randomized, controlled trials (RCTs) performed more than a decade ago. We performed a systematic review to understand current efficacy and safety data of lipiodol TACE in treatment of HCC. A search of the literature published between January 1, 1980 and June 30, 2013 was performed using MEDLINE and EMBASE databases. All potentially relevant publications were reviewed and articles were selected based on predefined inclusion and exclusion criteria. Of a total of 1,564 articles reviewed, 101 articles, including a total of 10,108 patients treated with lipiodol TACE, were selected for the efficacy analysis. Objective response rate was 52.5% (95% confidence interval [CI]: 43.6-61.5). Overall survival (OS) was 70.3% at 1 year, 51.8% at 2 years, 40.4% at 3 years, and 32.4% at 5 years. Median OS was 19.4 months (95% CI: 16.2-22.6). A total of 217 articles presenting precise description on numbers of adverse events (AEs) were selected for the safety review: In these studies, a total of 21,461 AEs were reported in 15,351 patients. Liver enzyme abnormalities were the most commonly observed AE, followed by the symptoms associated with postembolization syndrome. Overall mortality rate was 0.6% and the most common cause of death was related to acute liver insufficiency. Conclusions: In a systematic literature review, survival figures of HCC patients undergoing lipiodol TACE appear to be in line with those reported in previous RCTs, and no new or unexpected safety concerns were identified. (Hepatology 2016;64:106â\u80\u93116)