Maria Isabel Real

Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial

BACKGROUND There is no standard treatment for unresectable hepatocellular carcinoma. Arterial embolisation is widely used, but evidence of survival benefits is lacking. METHODS We did a randomised controlled trial in patients with unresectable hepatocellular carcinoma not suitable for curative treatment, of Child-Pugh class A or B and Okuda stage I or II, to assess the survival benefits of regularly repeated arterial embolisation (gelatin sponge) or chemoembolisation (gelatin sponge plus doxorubicin) compared with conservative treatment. 903 patients were assessed, and 112 (12%) patients were finally included in the study. The primary endpoint was survival. Analyses were by intention to treat. FINDINGS The trial was stopped when the ninth sequential inspection showed that chemoembolisation had survival benefits compared with conservative treatment (hazard ratio of death 0.47 [95% CI 0.25-0.91], p=0.025). 25 of 37 patients assigned embolisation, 21 of 40 assigned chemoembolisation, and 25 of 35 assigned conservative treatment died. Survival probabilities at 1 year and 2 years were 75% and 50% for embolisation; 82% and 63% for chemoembolisation, and 63% and 27% for control (chemoembolisation vs control p=0.009). Chemoembolisation induced objective responses sustained for at least 6 months in 35% (14)of cases, and was associated with a significantly lower rate of portal-vein invasion than conservative treatment. Treatment allocation was the only variable independently related to survival (odds ratio 0.45 [95% CI 0.25-0.81], p=0.02). INTERPRETATION Chemoembolisation improved survival of stringently selected patients with unresectable hepatocellular carcinoma.

Preoperative Staging and Tumor Resectability Assessment of Pancreatic Cancer: Prospective Study Comparing Endoscopic Ultrasonography, Helical Computed Tomography, Magnetic Resonance Imaging, and Angiography

OBJECTIVES:The objective of this study was to evaluate prospectively the efficacy of different strategies based on endoscopic ultrasonography (EUS), helical computed tomography (CT), magnetic resonance imaging (MRI), and angiography (A) in the staging and tumor resectability assessment of pancreatic cancer.METHODS:All consecutive patients with pancreatic carcinoma judged fit for laparotomy were studied by EUS, CT, MRI, and A. Results of each of the imaging techniques regarding primary tumor, locoregional extension, lymph-node involvement, vascular invasion, distant metastases, tumor TNM stage, and tumor resectability were compared with the surgical findings. Univariate, logistic regression, decision, and cost minimization analyses were performed.RESULTS:Sixty-two patients with pancreatic cancer were included. Helical CT had the highest accuracy in assessing extent of primary tumor (73%), locoregional extension (74%), vascular invasion (83%), distant metastases (88%), tumor TNM stage (46%), and tumor resectability (83%), whereas EUS had the highest accuracy in assessing tumor size (r = 0.85) and lymph node involvement (65%). The decision analysis demonstrated that the best strategy to assess tumor resectability was based on CT or EUS as initial test, followed by the alternative technique in those potentially resectable cases. Cost minimization analysis favored the sequential strategy in which EUS was used as a confirmatory technique in those patients in whom helical CT suggested resectability of the tumor.CONCLUSIONS:Helical CT and EUS are the most useful individual imaging techniques in the staging of pancreatic cancer. In those cases with potentially resectable tumors a sequential approach consisting of helical CT as an initial test and EUS as a confirmatory technique seems to be the most reliable and cost minimization strategy.

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).

MRA is useful as a follow-up technique after endovascular repair of aortic aneurysms with nitinol endoprostheses

To evaluate whether MR angiography (MRA) is a useful tool for the follow‐up of aortic aneurysms treated with nitinol endoluminal grafts.

Value of Doppler Sonography for Predicting Clinical Outcome After Renal Artery Revascularization in Atherosclerotic Renal Artery Stenosis

The purpose of this study was to prospectively evaluate the usefulness of Doppler sonography for predicting blood pressure and renal function improvement after percutaneous renal angioplasty in patients with unilateral atherosclerotic renal artery stenosis.

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.

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.