Marta Burrel

Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using Drug Eluting Beads. Implications for clinical practice and trial design.

BACKGROUND & AIMS Transarterial chemoembolisation (TACE) improves survival of properly selected patients with hepatocellular carcinoma (HCC). Drug eluting beads (DEB) provide a calibrated and homogenous procedure while increasing efficacy. Outcome data applying this technology is lacking, and this is instrumental for clinical decision-making and for trial design. We evaluated the survival of HCC patients treated with DEB-TACE following a strict selection (preserved liver function, absence of symptoms, extrahepatic spread or vascular invasion). METHODS We registered baseline characteristics, the development of treatment-related adverse events, and the overall survival of all HCC patients treated by DEB-TACE from February 2004 to June 2010. RESULTS One hundred and four patients were treated with DEB-TACE. All but one were cirrhotic, 62.5% HCV+, 95% Child-Pugh A, 41 BCLC-A and 63 BCLC-B. Causes of DEB-TACE treatment in BCLC-A patients were: 35 unfeasible ablation, and six post-treatment recurrences. After a median follow-up of 24.5 months, 38 patients had died, two patients had received transplantation and 24 had received sorafenib because of untreatable tumour progression. Median survival of the cohort was 48.6 months (95% CI: 36.9-61.2), while it was 54.2 months in BCLC stage A and 47.7 months in stage B. Median survival after censoring follow-up at time of transplant/sorafenib was 47.7 (95%CI: 37.9-57.5) months. CONCLUSIONS These data validate the safety of DEB-TACE and show that the survival expectancy applying current selection criteria and technique is better than that previously reported. A 50% survival at 4 years should be considered when suggesting treatment for patients fitting into controversial scenarios such as expanded criteria for transplantation/resection for multifocal HCC.

Transcatheter treatment of hepatocellular carcinoma with doxorubicin-loaded dc bead (DEBDOX): Technical recommendations

Tranarterial chemoembolization (TACE) has been established by a meta-analysis of randomized controlled trials as the standard of care for nonsurgical patients with large or multinodular noninvasive hepatocellular carcinoma (HCC) isolated to the liver and with preserved liver function. Although conventional TACE with administration of an anticancer-in-oil emulsion followed by embolic agents has been the most popular technique, the introduction of embolic drug-eluting beads has provided an alternative to lipiodol-based regimens. Experimental studies have shown that TACE with drug-eluting beads has a safe pharmacokinetic profile and results in effective tumor killing in animal models. Early clinical experiences have confirmed that drug-eluting beads provide a combined ischemic and cytotoxic effect locally with low systemic toxic exposure. Recently, the clinical value of a TACE protocol performed by using the embolic microsphere DC Bead loaded with doxorubicin (DEBDOX; drug-eluting bead doxorubicin) has been shown by randomized controlled trials. An important limitation of conventional TACE has been the inconsistency in the technique and the treatment schedules. This limitation has hampered the acceptance of TACE as a standard oncology treatment. Doxorubicin-loaded DC Bead provides levels of consistency and repeatability not available with conventional TACE and offers the opportunity to implement a standardized approach to HCC treatment. With this in mind, a panel of physicians took part in a consensus meeting held during the European Conference on Interventional Oncology in Florence, Italy, to develop a set of technical recommendations for the use of DEBDOX in HCC treatment. The conclusions of the expert panel are summarized.

Research Reporting Standards for Radioembolization of Hepatic Malignancies

Primary Liver Tumors Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver; its incidence is increasing worldwide. It ranks as the sixth most common tumor and third most common cause of cancer-related mortality (1,2). Primary liver tumors include HCC and intrahepatic cholangiocarcinoma. Surgical resection is preferred over transplantation and is considered potentially curative in patients with resectable HCC and normal liver function (3). Transplantation is considered the gold standard for patients with unresectable HCC and whose disease is within the Milan criteria (4). Resection and transplantation have limited roles, given advanced disease (chronic liver disease and/or tumor extent) at presentation and limited organ availability (5–7). Chemoembolization and radiofrequency ablation represent standard therapies in treating patients and serve as a bridge to transplantation in selected patients (8,9). Radioembolization has an emerging role in “bridging” patients within criteria by delaying tumor progression. It has also been shown to downstage disease beyond the Milan, to within, transplant criteria (10–12). A recent study has demonstrated that radioembolization leads to longer time-to-progression and better toxicity profile when compared with chemoembolization (13). Patients with macrovascular tumor involvement have also exhibited evidence of clinical benefit after radioembolization (14).

Clinical decision making and research in hepatocellular carcinoma: Pivotal role of imaging techniques

I maging techniques are a key tool for clinical decision making in the evaluation of patients with liver tumors. The development of ultrasound (US), computed tomography (CT), and magnetic resonance (MR) has allowed the detection and diagnosis of liver tumors at an asymptomatic stage, and this has modified their diagnostic approach and treatment. Indeed, some of the effective therapies are image guided. Furthermore, evaluation of treatment and follow-up are done through imaging. Hence, understanding of the information provided by imaging techniques is critical for the clinician in charge of liver cancer patients. Three major scenarios frame the clinical problem. The more common is formed by healthy individuals without liver disease and no previous cancer. Most will be diagnosed with a benign condition. Patients with a history of cancer should be suspected to present with metastases, whereas those with underlying liver disease should be considered at risk of liver cancer. In most, this will correspond to hepatocellular carcinoma (HCC), but occurrence of intrahepatic cholangiocarcinoma (ICC) is also increasing. This review summarizes the current knowledge about the use of imaging techniques for the diagnosis of primary liver cancer and the evaluation of treatment efficacy.

Endovascular Treatment of a Giant Intracranial Aneurysm with a Stent-Graft

This report describes a giant intracavernous carotid aneurysm successfully treated by the placement of a single covered stent. A 40-year-old woman was admitted with a progressive diplopia in relation with palsy of the IV and VI cranial nerves. Magnetic resonance imaging revealed an intracavernous giant aneurysm located at the bifurcation between the origin of a trigeminal artery and the intracavernous portion of the right internal carotid artery. A covered stent was successfully placed, and complete exclusion of the aneurysm was confirmed at 11-month follow-up angiography. The use of covered stents in intracranial vascular structures can now be a feasible way of treating selected cases of wide-necked intracranial aneurysms.

Utility of Multidetector CT in Severe Postpartum Hemorrhage

Postpartum hemorrhage is one of the leading causes of maternal mortality worldwide. According to the time when postpartum hemorrhage develops, it is classified as (a) primary, or early, postpartum hemorrhage (within the first 24 hours after delivery) or (b) secondary, or late, postpartum hemorrhage (>24 hours to 6 weeks after delivery). Primary postpartum hemorrhage may be caused by uterine atony (75%-90% of cases), trauma of the lower portion of the genital tract, uterine rupture, uterine inversion, bladder flap hematoma, retention of blood clots or placental fragments, and coagulation disorders. Secondary postpartum hemorrhage may be caused by uterine subinvolution, coagulopathies, and abnormalities of the uterine vasculature. Extrauterine sources of bleeding include rectus sheath hematoma, direct arterial injuries, and the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Severe postpartum hemorrhage is a life-threatening condition that is diagnosed on the basis of the findings from clinical examination, with or without ultrasonography. Computed tomography (CT) and magnetic resonance imaging are useful in the characterization of postpartum hemorrhage when medical treatment fails. Multidetector CT has an important role when intraabdominal bleeding is suspected and can be considered in cases of recurrent bleeding after embolization, as well as for the evaluation of postsurgical complications. A proposed clinical and CT imaging algorithm for postpartum hemorrhage is presented. A multidisciplinary approach to postpartum hemorrhage is essential to optimize the role of diagnostic and interventional radiology in obstetric hemorrhage, to avoid hysterectomy and thus preserve fertility.

Diagnóstico y tratamiento del carcinoma hepatocelular. Actualización del documento de consenso de la AEEH, SEOM, SERAM, SERVEI y SETH

Hepatocellular carcinoma is the most common primary malignancy of the liver and one of the most frequent causes of death in patients with liver cirrhosis. Simultaneously with the recognition of the clinical relevance of this neoplasm, in recent years there have been important developments in the diagnosis, staging and treatment of HCC. Consequently, the Asociación Española para el Estudio del Hígado has driven the need to update clinical practice guidelines, continuing to invite all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document (Sociedad Española de Trasplante Hepático, Sociedad Española de Radiología Médica, Sociedad Española de Radiología Vascular e Intervencionista y Sociedad Española de Oncología Médica). The clinical practice guidelines published in 2009 accepted as Clinical Practice Guidelines of the National Health System has been taken as reference document, incorporating the most important advances that have been made in recent years. The scientific evidence for the treatment of HCC has been evaluated according to the recommendations of the National Cancer Institute (www.cancer.gov) and the strength of recommendation is based on the GRADE system.

Evaluation of Abdominal Aortic Aneurysm after Endovascular Repair: Prospective Validation of Contrast-enhanced US with a Second-Generation US Contrast Agent

PURPOSE To prospectively assess the accuracy of contrast agent-enhanced (CE) ultrasonography (US) with a second-generation US contrast agent in the detection and classification of endoleaks after endovascular repair of abdominal aortic aneurysms (EVAR), with computed tomographic (CT) angiography as the reference standard. MATERIALS AND METHODS Institutional review board and written informed consent were obtained. Thirty-five patients who underwent EVAR were enrolled in a prospective study that consisted of CT angiography and CE US studies performed at 1- and 6-month follow-up and performed yearly thereafter. CE US was performed after bolus injection of 2.4 mL of sulfur hexafluoride by using equipment with specific software for contrast studies. Angiography was performed in patients who had type II endoleaks with an increase in aneurysm sac size and in patients with type I or III endoleaks. CE US sensitivity, specificity, positive and negative predictive values, and accuracy were determined for endoleak detection, and Cohen κ statistic was used to assess agreement of CE US and CT angiographic findings for endoleak classification. RESULTS A total of 126 CT angiographic and CE US studies were performed. CT angiography depicted 34 endoleaks in 16 patients (type IA, n=1; type IB, n=1; type II inferior mesenteric artery, n=2; type II lumbar artery, n=28; type II complex, inferior mesenteric, and lumbar arteries, n=2). CE US depicted 33 endoleaks. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CE US in endoleak detection were 97%, 100%, 100%, 98%, and 99%, respectively. CE US enabled correct classification of 26 of 33 endoleaks. No clinically important endoleak was missed at CE US. CONCLUSION CE US yields good sensitivity, specificity, and accuracy in endoleak detection, and it might represent a noninvasive tool that can be used in the follow-up of patients who undergo EVAR.

Risk factors and outcomes of failed endoscopic retrograde cholangiopancreatography in liver transplant recipients with anastomotic biliary strictures: A case‐control study

Anastomotic strictures (ASs) of the biliary duct after liver transplantation (LT) are primarily managed with endoscopic retrograde cholangiopancreatography (ERCP), but in some cases, this fails because of difficulties in passing the strictures. The aim of this case‐control study was to examine specific risk factors for initial ERCP failure and the outcomes of percutaneous transhepatic cholangiography (PTC) as a second‐line approach in LT recipients with ASs. Between January 2002 and December 2010, we identified LT recipients with ASs who experienced initial ERCP failure (which was defined as the inability to traverse the AS with guidewires in 2 or more consecutive procedures). A period‐matched control group (ratio = 1:2) with ASs and initial ERCP success was analyzed. Preoperative, intraoperative, postoperative, and endoscopic variables were evaluated as risk factors. The outcomes of PTC and the need for hepaticojejunostomy (HJ) or retransplantation were evaluated. Seventeen cases who experienced initial ERCP failure were compared with 34 controls. The median times from LT to ERCP were similar (8.7 months for cases and 8.6 months for controls, P = not significant). A multivariate analysis revealed that previous bile leaks [odds ratio (OR) = 6.07, 95% confidence interval (CI) = 1.0‐36.5] and more than 4 U of intraoperatively transfused red blood cells (OR = 11.51, 95% CI = 1.9‐71.2) were independent risk factors for failure. PTC was an effective second‐line treatment in only 3 of 12 cases (25%). The need for HJ was more frequent for the cases (13/17 or 76.5%) versus the controls (7/34 or 20.6%, P < 0.001). One patient in each group underwent retransplantation (P = not significant). In conclusion, previous bile leaks and high packed red blood cell transfusion requirements during surgery are risk factors for initial ERCP failure in LT recipients with ASs. A high proportion of these patients will need surgery as their final therapy. Liver Transpl 18:482–489, 2012.

Single reading with computer-aided detection performed by selected radiologists in a breast cancer screening program.

OBJECTIVES To assess the impact of shifting from a standard double reading plus arbitration protocol to a single reading by experienced radiologists assisted by computer-aided detection (CAD) in a breast cancer screening program. METHODS This was a prospective study approved by the ethics committee. Data from 21,321 consecutive screening mammograms in incident rounds (2010-2012) were read following a single reading plus CAD protocol and compared with data from 47,462 consecutive screening mammograms in incident rounds (2004-2010) that were interpreted following a double reading plus arbitration protocol. For the single reading, radiologists were selected on the basis of the appraisement of their previous performance. RESULTS Period 2010-2012 vs. period 2004-2010: Cancer detection rate (CDR): 6.1‰ (95% confidence interval: 5.1-7.2) vs. 5.25‰; Recall rate (RR): 7.02% (95% confidence interval: 6.7-7.4) vs. 7.24% (selected readers before arbitration) and vs. 3.94 (all readers after arbitration); Predictive positive value of recall: 8.69% vs. 13.32%. Average size of invasive cancers: 14.6±9.5mm vs. 14.3±9.5mm. Stage: 0 (22.3/26.1%); I (59.2/50.8%); II (19.2/17.1%); III (3.1/3.3%); IV (0/1.9%). Specialized breast radiologists performed better than general radiologists. CONCLUSIONS The cancer detection rate of the screening program improved using a single reading protocol by experienced radiologists assisted by CAD, at the cost of a moderate increase of the recall rate mainly related to the lack of arbitration.