Drug-eluting Microspheres Compared to Conventional Transarterial Chemoembolization as First Line Treatment for Unresectable Hepatocellular Carcinoma: A Single-center Retrospective Cost-utility Analysis.

PURPOSE: To assess the cost-utility of initial treatment with drug-eluting microspheres (DEM) transarterial chemoembolization (TACE) versus conventional (C)-TACE in patients with hepatocellular carcinoma considering the perspective of a Local Healthcare Authority in Italy. MATERIALS AND METHODS: The economic evaluation is based on a retrospective single-center study and individual patients' data whose details have been previously reported. The impact of initial treatment with DEM-TACE or C-TACE on disease progression, mortality, and direct health costs over a lifetime horizon were simulated and compared in terms of incremental cost-utility ratio expressed as costs per quality adjusted life years (QALY). Costs included direct health costs related to the first chemoembolization procedure and all subsequent follow-up costs associated with health care resources used for disease management. Probabilistic (PSA) sensitivity analysis was used to assess the robustness of the results. RESULTS: A total of 101 patients in each treatment group were considered. All over the time-horizon median costs were €3,145.14 and €2,158.32 in the DEM-TACE and C-TACE group, respectively (p < 0.001); while mean costs were € 24,619 and € 17,001, respectively (p < 0.001). The ICUR was 6,461.86 €/QALY when using median costs derived from the study population as input for the health-economic evaluation and 49,932.15 €/QALY when the mean costs were considered. Results from PSA highlighted that using median costs DEM-TACE was always cost-effective, while using mean costs, it was preferable only 24.7% of times. CONCLUSIONS: The higher prices of DEMs are counterbalanced by the positive impact on QALY.

Loco-regional treatment of HCC: current status.

Hepatocellular carcinoma (HCC) represents one of the few cancers for which locoregional treatments are recognised as being able to cure and/or prolong survival and are included in international guidelines. This is due to the unique nature of HCC, in most cases occurring in patients with underlying virus- or alcohol-related cirrhosis. The treatment choice in patients with HCC is therefore driven not only by tumour staging, as in the great majority of cancers, but also by careful evaluation of liver function and physical status. Another specific feature of HCC is that it is the only tumour that can be cured by organ transplantation, with the aim of treating both the cancer and underlying liver disease. These characteristics configure a complex scenario and prompt the need for close cooperation among interventional oncologists, surgeons, hepatologists, and anaesthesiologists. In patients with limited hepatic disease, preserved hepatic function and good performance status, categorised as very early and early-stage HCC according to the Barcelona Clinic Liver Cancer (BCLC) classification, image-guided tumour ablation is included among the curative treatments. More than half of patients with HCC are, however, diagnosed late, despite the widespread implementation of surveillance programmes, when curative treatments cannot be applied. For patients presenting with multinodular HCC and relatively preserved liver function, absence of cancer-related symptoms, and no evidence of vascular invasion or extrahepatic spread transcatheter arterial chemoembolisation (TACE) is the current standard of care. Although anti-tumour activity and promising survival results has been reported in cohorts of patients with advanced HCC treated with radio-embolisation, systemic treatment with the multi-kinase inhibitor, sorafenib, is still recommended for patients at this stage. In this article, current treatment strategies for HCC according to tumour stage are discussed, underlining the latest advances in the literature and technical developments.

iPad-based primary 2D reading of CT angiography examinations of patients with suspected acute gastrointestinal bleeding: preliminary experience.

OBJECTIVE: To evaluate the effectiveness of the iPad (Apple Inc., Cupertino, CA) for two-dimensional (2D) reading of CT angiography (CTA) studies performed for suspected acute non-variceal gastrointestinal bleeding. METHODS: 24 CTA examinations of patients with suspected acute gastrointestinal bleeding confirmed (19/24, 79.2%) or ruled out (5/24, 20.8%) by digital subtraction angiography (DSA) were retrospectively reviewed by three independent readers on a commercial picture archiving communication system (PACS) workstation and on an iPad with Retina Display® 64 GB (Apple Inc.). The time needed to complete reading of every CTA examination was recorded, as well as the rate of detection of arterial bleeding and identification of suspected bleeding arteries on both devices. RESULTS: Overall, the area under the receiver operating characteristic curve, sensitivity, specificity, positive- and negative-predictive values for bleeding detection were not significantly different while using the iPad and workstation (0.774 vs 0.847, 0.947 vs 0.895, 0.6 vs 0.8, 0.9 vs 0.944 and 0.750 vs 0.667, respectively; p > 0.05). In DSA-positive cases, the iPad and workstation allowed correct identification of the bleeding source in 17/19 cases (89.5%) and 15/19 cases (78.9%), respectively (p > 0.05). Finally, the time needed to complete reading of every CTA study was significantly shorter using the iPad (169 ± 74 vs 222 ± 70 s, respectively; p < 0.01). CONCLUSION: Compared with a conventional PACS workstation, iPad-based preliminary 2D reading of CTA studies has comparable diagnostic accuracy for detection of acute gastrointestinal bleeding and can be significantly faster. ADVANCES IN KNOWLEDGE: The iPad could be used by on-call interventional radiologists for immediate decision on percutaneous embolization in patients with suspected acute gastrointestinal bleeding.

Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma.

BACKGROUND: Transcatheter arterial chemoembolisation (TACE) is the treatment of choice for intermediate stage hepatocellular carcinoma (HCC). Doxorubicin-loaded drug-eluting beads (DEB)-TACE is expected to improve the performance of conventional TACE (cTACE). The aim of this study was to compare DEB-TACE with cTACE in terms of time-to-tumour progression (TTP), adverse events (AEs), and 2-year survival. METHODS: Patients were randomised one-to-one to undergo cTACE or DEB-TACE and followed-up for at least 2 years or until death. Transcatheter arterial chemoembolisation was repeated 'on-demand'. RESULTS: We enrolled 177 patients: 89 underwent DEB-TACE and 88 cTACE. The median number of procedures was 2 in each arm, and the in-hospital stay was 3 and 4 days, respectively (P=0.323). No differences were found in local and overall tumour response. The median TTP was 9 months in both arms. The AE incidence and severity did not differ between the arms, except for post-procedural pain, more frequent and severe after cTACE (P<0.001). The 1- and 2-year survival rates were 86.2% and 56.8% after DEB-TACE and 83.5% and 55.4% after cTACE (P=0.949). Eastern Cooperative Oncology Group (ECOG), serum albumin, and tumour number independently predicted survival (P<0.05). CONCLUSIONS: The DEB-TACE and the cTACE are equally effective and safe, with the only advantage of DEB-TACE being less post-procedural abdominal pain.

Efficacy and safety of combination therapy with everolimus and sorafenib for recurrence of hepatocellular carcinoma after liver transplantation.

BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is still associated with a dismal outcome. Combination therapy with everolimus (EVL) and vascular endothelial growth factor inhibitor sorafenib (SORA) is based on the role of both b-Raf and mammalian target of rapamycin/protein kinase B pathways in the pathogenesis of HCC and is being investigated in clinical practice. METHODS: This was a single-center retrospective analysis on LT recipients with unresectable HCC recurrence and undergoing combination therapy with EVL and SORA. Patients were included if they were switched to EVL+SORA at any time after surgery. Primary endpoint was overall survival (OS) after both LT and recurrence, and response to treatment based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) in the intention-to-treat (ITT) population. Secondary analysis was safety of combination therapy with EVL and SORA in the population of patients who received ≥1 dose of the study drug. RESULTS: Seven patients (100% male; median age 53 years [interquartile range (IQR) 9 years]) were considered for analysis. HCC recurrence was diagnosed at a median (IQR) interval since LT of 9 (126) months, and patients were administered EVL+SORA at a median interval since LT of 11 (126) months. Baseline immunosuppression was with tacrolimus (TAC) in 2 patients (28.6%), cyclosporine (CsA) in 2 (28.6%), and EVL monotherapy in 3 (42.8%). At a median (IQR) follow-up of 6.5 (14) months, 5 patients (71.4%) were alive, 4 of them (57.1%) with tumor progression according to the mRECIST criteria. Median (IQR) time to progression was 3.5 (12) months. Two patients died at a median (IQR) follow-up of 5 (1) months owing to tumor progression in 1 patient (14.3%) and sepsis in the other (14.3%). EVL monotherapy was achieved in 6 patients (85.7%), whereas 1patient (14.3%) could not withdraw from calcineurin inhibitor owing to acute rejection. Treatment complications were: hand-foot syndrome in 5 patients (71.4%), hypertension in 1 (14.3%), alopecia in 1 (14.3%), hypothyroidism in 1 (14.3%), diarrhea in 2 (28.6%), pruritus in 1 (14.3%), abdominal pain in 1 (14.3%), rash in 1 (14.3%), asthenia in 3 (42.8%), anorexia in 3 (42.8%), and hoarseness in 2 (28.6%). Adverse events led to temporary SORA discontinuation in 2 patients (28.6%) and to SORA dose reduction in 3 (42.8%). CONCLUSIONS: Treatment of HCC recurrence after LT with a combination regimen of EVL+ SORA is challenging because of SORA-related complications. Longer follow-up periods and larger series are needed to better capture the impact of such combination treatment on tumor progression and patient survival.

Intermediate hepatocellular carcinoma: current treatments and future perspectives.

Current guidelines recommend transarterial chemoembolization (TACE) as the standard treatment of Barcelona-Clinic Liver Cancer (BCLC)-B patients. However, the long-term survival outcomes of patients managed with this technique do not appear fully satisfactory; in addition, intermediate-stage hepatocellular carcinoma (HCC) includes a heterogeneous population of patients with varying tumour burdens, liver function and disease aetiology. Therefore, not all patients with intermediate-stage HCC may derive similar benefit from TACE, and some patients may benefit from other treatment options, which are currently approved or being explored. These include different TACE modalities, such as selective TACE or drug-eluting beads TACE and radioembolization. The introduction of sorafenib in the therapeutic armamentarium for HCC has provided a new therapeutic option for the treatment of BCLC-B patients who are unsuitable to TACE or in whom TACE resulted in unacceptable toxicity. In addition, clinical trials aimed at investigating the potential role of this molecule in the treatment of patients with intermediate-stage HCC within combination therapeutic regimens are ongoing. This narrative review will present and discuss the most recent evidence on the locoregional or medical treatment with sorafenib in patients with intermediate-stage HCC.

Contribution of contrast-enhanced ultrasonography to nonoperative management of segmental ischemia of the head of a pancreas graft.

A 32-year-old recipient of a pancreas transplant (PTx) alone was diagnosed with segmental graft ischemia, involving the head of the pancreas graft (HPG), based on color Doppler ultrasonography (CDU) and computed tomography (CT) angiography. For investigational purposes, graft supply was further checked by contrast-enhanced ultrasonography (CEU). Surprisingly, CEU showed collateral blood supply to the HPG starting from 40 s after contrast injection and resulting in homogenous parenchymography at 90 s. Full-dose heparin infusion, followed by long-term oral anticoagulation, allowed graft salvage without reoperation. At the longest follow-up of 18 months, the patient is insulin independent. This case report shows that CEU may be employed in PTx recipients suspected to harbor vascular complications. To the best of our knowledge, this is the first description of the use of CEU in PTx and the first description of graft salvage, without partial pancreatectomy after CDU and CT diagnosis of segmental graft ischemia.

False positive tardus-parvus waveforms after liver transplantation: a case of wide discrepancy between donor and recipient hepatic arteries mimicking anastomotic stenosis.

BACKGROUND: Parvus-tardus waveforms of the hepatic artery after liver transplantation usually indicate an arterial complication and severe impairment of hepatic arterial perfusion with a sensitivity of 91% and a specificity of 99.1%. Thus, it has been emphasized that detection of such waveforms should prompt emergency angiography. MATERIALS AND METHODS: Arterial reconstruction during a liver transplantation was successfully accomplished by an end-to-end anastomosis, performing a "flute-spout" widening of the anastomosis with a 7/0 prolene running suture between a small recipient proper hepatic artery and the donor common hepatic artery. RESULTS: On day 7 posttransplantation color Doppler ultrasonography revealed a parvus-tardus waveform pattern in the hepatic arterial flow. Computed tomographic (CT) angiography showed only a caliber discrepancy between the donor and recipient stumps, excluding an arterial stenosis or thrombosis. Since normal liver function persisted, the patient underwent routine follow-up. After 15 months the patient was alive and well; hepatic artery spectral waveforms were unchanged and liver functions were consistent with a mild hepatitis C virus (HCV) recurrence. CONCLUSIONS: This is a report of false positive tardus-parvus waveforms, due to a discrepancy between the donor and recipient arteries despite a wide anastomosis. Knowledge of technical reconstruction details may be helpful for correct interpretation of color Doppler findings. CT angiography should be considered before more invasive examinations.

Diagnosis and treatment of hepatic artery stenosis after orthotopic liver transplantation.

PURPOSE: The purpose of this study was to evaluate the accuracy of Multidetector Computed Tomographic Angiography (MDCTA) to detect hepatic artery (HA) stenosis after orthotopic liver transplantation (OLT) and the efficacy of treatment using percutaneous transluminal angioplasty (PTA). MATERIALS AND METHODS: Twenty-two consecutive patients with OLT underwent MDCTA for evaluation of HA, followed by digital subtraction angiography (DSA) (gold standard). Source images (Ax) were processed, obtaining multiplanar reformations (MPRs), maximum intensity projections (MIPs), and volume renderings (VRs). Images were evaluated to identify the following: (1) arterial depiction (celiac axis, anastomosis, and left [LHA] and right [RHA] HA), (2) detection of stenoses, and (3) grading of stenoses. Indications for PTA were set at MDCTA and DSA, and PTA was performed when appropriate. RESULTS: MDCTA depicted the celiac axis and anastomoses in all patients; LHA and RHA were visualized in 21 of 22 patients with Ax, MPRs, and MIPs, and in 17 of 22 with VRs. All reconstruction modalities enabled correct diagnosis of celiac (n = 3) and anastomotic stenoses (n = 14). Of 6 LHA and RHA stenoses, 4 (66.7%) were visualized with Ax, MPRs, and VRs, and 5 (83.3%) were visualized with MIPs. Stenosis was overestimated in 9 (39.1%) cases with VRs and in 3 (13%) with the other modalities. PTA was performed in 8 cases, with 1 case of arterial dissection requiring re-OLT. At a median follow-up of 28 months, the primary and secondary patency rates were 71.4% (5 of 7) and 85.7% (6 of 7), respectively. CONCLUSIONS: MDCTA and accurate postprocessing enable confident depiction of the arterial anatomy and detection of stenosis after OLT. PTA is safe and allows allograft saving, at least until another suitable donor becomes available.

Role of interventional radiology in the management of vascular complications after liver transplantation.

The purpose of this study is to review the role of the percutaneous interventional procedures in the treatment of vascular complications after orthotopic liver transplantations (OLT). Vascular complications, such as arterial stenosis and venous thrombosis, which occur in approximately 1% to 10% of liver transplant patients, are associated with a higher risk of graft dysfunction. Percutaneous interventional procedures, including angioplasty, local thrombolysis, and embolization, are useful to manage these complications. A reduced blood loss and a low incidence of procedural complications allow for rapid recovery. Hepatic arterial and portal vein anastomotic stenosis can be treated effectively by means of balloon dilation; stenting has also been proposed, particularly for venous complications. Infusional local thrombolysis may be useful in venous thrombosis. Arteriovenous fistulas, occurring at the level of the anastomosis or after liver biopsy, require intraarterial embolization using microcoils or gelfoam. Timing of the intervention for the treatment of ischemic complications is of outmost importance to guarantee liver functional recovery and avoid irreversible parenchymal injuries. Other interventional procedures may be extremely useful to manage portal hypertension after OLT; for example, by creation of transjugular portosystemic shunts, or, in the case of associated hypersplenism, transarterial embolization of the splenic artery. Finally, in patients with recurrent hepatitis, the transjugular approach has been shown to be safe and effective for liver biopsy, whereas transarterial chemoembolization may be extremely useful to treat recurrent hepatocarcinoma.

Duplex ultrasonographic study of the renal arteries before and after renal artery stenting.

The aim of our study was to evaluate feasibility and accuracy of colour-coded duplex US in the detection of renal artery stenosis before and after stenting. Eighty-four patients (23 women, 61 men; mean age 64 years) with significant renal artery stenosis were studied with Doppler US, before and after stenting. A combined anterior and translumbar approach was used to visualise the renal arteries. Renal artery stenosis and in-stent restenosis were proved by the increase of renal peak systolic velocity (PSV) and reno-aortic ratio (RAR). Laboratory-specific threshold values of PSV and RAR were used to assess sensitivity and specificity of Doppler US. The renal arteries were visualised in all patients (feasibility 100%). A statistically significant difference of PSV and RAR was demonstrated between patent and stenotic renal arteries, before stenting, and between stenotic and stented renal arteries. No difference was demonstrated in cases of in-stent restenosis ( n=21). Before stenting, sensitivity of PSV and RAR was 93%, whereas specificity rates were 92 and 96%, respectively. After stenting sensitivity and specificity rates were, respectively, 90 and 93% for PSV, and 95 and 95% for RAR. Doppler US represents a feasible and reliable technique in the detection of renal artery stenosis and in-stent restenosis, although laboratory-specific threshold values are required to improve its accuracy.

[CT virtual angioscopy in the study of thoracic aortic dissection]. / Angioscopia virtuale con TC spirale nello studio delle dissecazioni dell'aorta toracica.

PURPOSE: Virtual endoscopy is a technique in which helical-CT and MR data sets are processed by a special software creating a three-dimensional viewing of the inner surface of hollow viscera that simulates the endoscopic view. We report our 2.5-year experience with virtual intraluminal endoscopy (VIE) in the study of the thoracic aorta in patients with aortic dissection and in patients with normal aorta. MATERIAL AND METHODS: From December 1997 to June 2000, CT angiography (CTA) data sets of the thoracic aorta obtained in a series of 43 patients were retrospectively evaluated. Our series included 23 patients with clinical or radiological suspicion of aortic dissection and 20 patients in whom the study of the thoracic aorta was carried out as a necessary completion of an abdominal aortic disease. CTA data sets were processed with a dedicated software (Navigator); the view point and view direction could be set arbitrarily in the vessel, obtaining an intraluminal endoscopic view of the inner surface of the vessel. Multiple views were obtained and visualised consecutively through a cine-loop technique. The entire thoracic aorta was studied. RESULTS: VIE enabled correct visualisation of the intimal flap in all cases of aortic dissection (=23) and of its origin at the level of the ascending aorta in 16 cases (Stanford A) and in the descending aorta in the remaining 7 patients (Stanford B). In the control group (=20) no signs of intimal flap were identified with the VIE. In all patients with aortic dissection false and true lumen were entirely visualised. VIE allowed the understanding of the relation between false lumen and supraaortic vessels that originated from the true lumen in all cases and were found to be dissected in 6 patients. In 16 cases the dissection included thoracic and abdominal aorta. In some cases the endoscopic view was altered by artifacts related to the selected threshold levels and represented by pierced surface and floating shape artifacts. A correlation with axial and multiplanar (MPR) images allowed the correct interpretation of such artifacts. CONCLUSIONS: According to our experience, virtual endoscopy represents a useful tool in the evaluation of the dissection of the thoracic aorta, allowing a better definition of anatomical details. A correlation with axial images and multiplanar views remains compulsory for a better understanding of VIE findings, which is nevertheless significantly influenced by the operator's experience.

Endoluminal treatment of abdominal aortic aneurysms.

BACKGROUND: We report our preliminary results with endovascular treatment of abdominal aortic aneurysms (AAA). METHODS: Between October 1998 and June 2000, 64 patients (62 male, two female; mean age = 70 years) underwent endovascular repair of AAA. Different types of prostheses were used, both bifurcated (n = 58) and straight (n = 6). We performed duplex sonography and spiral computed tomographic angiography (CTA) at discharge and at 3, 6, 12, and 18 months. Follow-up ranged from 1 to 20 months. RESULTS: All procedures were successful, except for three immediate and one late surgical conversions (6.2%). One patient died 14 days after immediate surgical conversion. At discharge, CTA showed 13 endoleaks: three resolved spontaneously, six persisted during follow-up, and four (one angioplasty and three embolizations) were treated successfully. Stenosis of an iliac branch occurred in one patient after 3 months and was successfully treated by angioplasty. Late endoleaks were detected by imaging follow-up in four cases, three at 1 year and one at 6 months, requiring deployment of distal extender cuffs (n = 2), a proximal cuff (n = 1), and lumbar embolization (n = 2). CONCLUSION: Our preliminary experience supports the efficacy of endovascular repair in selected patients, but strict and accurate follow-up is required.

Renal artery stenting in patients with a solitary functioning kidney.

PURPOSE: To retrospectively evaluate the results of renal artery stenting in patients with renovascular disease and a solitary functioning kidney. METHODS: Palmaz stents were placed in 16 patients with a solitary functioning kidney, renal artery stenosis, hypertension and renal failure. Stenoses were evaluated with color Doppler ultrasound, MR angiography and digital subtraction angiography (DSA). Indications for stenting were: recoil after percutaneous transluminal renal angioplasty (PTRA) (63%), arterial dissection after PTRA (13%) and primary stenting (25%). Immediate results were evaluated by DSA. On follow-up (6-36 months), patients underwent periodical evaluation of clinical conditions (blood pressure and serum creatinine level) and stent patency, by means of color Doppler ultrasound. RESULTS: Stent placement was successful in all patients (100%). Cumulative primary patency rate was: 100% at 1 day, 93.75% at 6 months, 81.25% at 12 months and 75% at 24 months. A significant reduction in diastolic blood pressure occurred (mean +/- SD 104 +/- 6 vs 92 +/- 3; p < 0.05); renal function improved or stabilized in over 80% of patients. However, there was no significant difference in the creatinine values before and after treatment (mean +/- SD 200 +/- 142 micromol/l vs 197 +/- 182 micromol/l; p > 0.05). CONCLUSION: Renal artery stenting, both after PTRA and as primary stenting, represents a safe procedure, able to preserve renal function in patients with a solitary functioning kidney.