Transarterial Chemoembolization Procedures Research Articles

Morbidity and mortality following transarterial liver chemoembolization in patients with hepatocellular carcinoma and synthetic hepatic dysfunction

The purpose of this study was to determine the rate and risk factors for the development of irreversible hepatotoxicity after transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) and synthetic hepatic dysfunction. Two hundred fifty-one consecutive patients with HCC and hepatic dysfunction who underwent 443 TACE procedures from 2005 to 2010 were retrospectively reviewed. The included patients met one of the following criteria: a pre-TACE bilirubin level ≥ 2 mg/dL, an international normalized ratio (INR) > 1.5, a creatinine level > 1.2 mg/dL, a platelet count ≤ 60,000/mL, a Model for End-Stage Liver Disease (MELD) score > 15, Child-Turcotte-Pugh class B or C, ascites, or portal vein thrombosis. Hepatotoxicity was defined as new or worsening ascites, encephalopathy, or grade 3 or 4 toxicity (bilirubin, aspartate aminotransferase, alanine aminotransferase, creatinine, or INR) according to the National Cancer Institute Common Terminology Criteria for Adverse Events. The rate and risk factors for death or urgent liver transplantation within 6 weeks of TACE and irreversible hepatotoxicity were determined with a generalized estimating equation analysis. Reversible hepatotoxicity developed after 90 procedures (20%) in 78 patients (31%). Irreversible hepatotoxicity developed after 41 procedures (9%) in 37 patients (15%). Six patients (2%) underwent urgent liver transplantation, and 11 (4%) died within 6 weeks of TACE. Patients at increased risk for procedure-related mortality or urgent liver transplantation within 6 weeks of TACE had a baseline serum bilirubin level ≥ 4.0 mg/dL (P = 0.01), an elevated INR (P < 0.001), hypoalbuminemia with an albumin level < 2.0 g/L (P = 0.01), a serum creatinine level > 2.0 mg/dL (P = 0.02), large ascites (P = 0.002), encephalopathy (P = 0.005), or a MELD score ≥ 20 (P < 0.001). In conclusion, TACE can be performed safely in patients with baseline hepatic dysfunction. However, a poor hepatic reserve increases the risk of irreversible hepatotoxicity, which may lead to death or the need for urgent liver transplantation.

Clinical factors related to long-term administration of sorafenib in patients with hepatocellular carcinoma

BackgroundSorafenib has been approved in the indication of unresectable hepatocellular carcinoma, but there are many cases in which administration of the drug is discontinued due to severe side effects. In this study, we compared the characteristics of patients who continued and discontinued sorafenib.MethodsNinety-six patients (75 men and 21 women) were initiated on sorafenib from July 2009 through September 2011. The patient characteristics of interest included gender, age, etiology, Child-Pugh classification, treatment history and frequency, and levels of α-fetoprotein, des- gamma-carboxy prothrombin, aspartate amino acid transferase, and alanine aminotransferase. Duration of administration of sorafenib and reasons for its discontinuation were compared.ResultsMedian overall survival was 11.8 months. Discontinuation of sorafenib within 90 days was identified as an independent prognostic factor for overall survival on multivariate analysis (P < 0.0001). Transarterial chemoembolization performed six times or more (P = 0.013) was also identified as an independent factor contributing to discontinuation of sorafenib within 90 days in multivariate analysis. Patients who received sorafenib for ≥90 days had significantly longer overall survival than those who discontinued it (P < 0.0001).ConclusionProlonged treatment with sorafenib is an important factor in achieving extended overall survival. We recommend starting sorafenib before latent liver damage has occurred as a result of too many transarterial chemoembolization procedures.

Drug eluting beads on cytology smears

To the Editor, Transarterial chemoembolization (TACE) is the most widely used primary treatment for unresectable hepatocellular carcinoma (HCC). TACE increases the in-situ dwell time and concentration of drug through vascular occlusion by drug-eluting beads (DEB). DEB consist of injectable polymeric microspheres of calibrated size that can be loaded with various antineoplastic solutions.[1] We describe here the appearance of doxorubicin drug eluding beads on cytology in a 60-year-old African-American male with a past medical history of hepatitis C, hypertension, HCC, hypothyroidism, and arthritis. The patient underwent three TACE procedures within the year for treatment of HCC. Four months after the last chemoembolization, a computed tomography (CT) scan showed a suspicious lesion next to the TACE area. An ultrasound guided fine needle aspiration and core biopsies were done of the suspicious lesion. The cytology showed moderately cellular smears composed of groups of neoplastic cells with endothelial wrapping consistent with HCC. Intermixed with hepatocytes were circumscribed dense eosinophilic globules consistent with the DEB from chemoembolization [Figures ​[Figures11–3], done 4 months ago. The core biopsy showed nests of malignant cells with focal pseudoacinar pattern, in background of cirrhosis. On reticulin stain the tumor showed decreased staining with thickened trabeculae confirming the diagnosis of HCC seen on smears. A total of four fine needle passes and two 18 gauge core biopsies were done. The chemoembolization beads were seen only in one air dried smear. Figure 1 Drug eluting beads on cytology smear (4× diff quik stain) Figure 3 drug eluting beads on cytology smear (4× diff quik stain) Figure 2 Drug eluting beads on cytology smear (4× diff quik stain) Developed in mid-2000, DEB can be loaded with cytotoxic drugs for the chemoembolization of hypervascular tumors.[2] These beads slowly release the cytotoxic drug in a controlled fashion into the tumor, inflicting local ischemia while reducing systemic drug concentrations.[2] In our patient the doxorubicin eluting beads were used. These were seen as homogenous, well circumscribed purple, foreign body globules measuring in size from 100–300 μm on air dried cytology smears stained with Romanowsky stain [Figures ​[Figures11–3]. Previously described microscopic appearance of drug eluting and radioactive beads has been reported in histology tissue sections.[1,3–5] The rationale of using these DEB is based on the assumption that the vector releases its chemotherapeutic agent, which is able to diffuse locally in the embolized area and causes the necrosis of the target tissue.[1] The tissue adjacent to beads shows characteristic coagulative necrosis and an inflammatory–fibrotic reaction few weeks after the procedure. The DEB have been demonstrated in the tissue sections from explanted liver, but to our knowledge they have not yet been described in a cytology preparation. In the current case we did see a foreign body type giant cell [Figure 4] but did not see any necrosis or fibro-inflammatory reaction adjacent to the beads. Figure 4 Foreign body type of giant cell (400× diff quik stain)

Safety and Feasibility of Same-day Discharge of Patients with Unresectable Hepatocellular Carcinoma Treated with Doxorubicin Drug-eluting Bead Transcatheter Chemoembolization

PurposeThe aim of this study was to investigate the safety and feasibility of same-day discharge of patients with unresectable hepatocellular carcinoma (HCC) after doxorubicin drug-eluting bead (DEB) transarterial chemoembolization and to elucidate the factors predisposing to overnight admission. Materials and MethodsConsecutive patients with unresectable HCC who underwent superselective 100–300 μm DEB transarterial chemoembolization were included. The parameters of same-day therapy (group A) were compared with those of patients admitted overnight (group B). A χ2 test and a t test were used to compare categorical and continuous variables accordingly. ResultsSeventy-six patients (mean, 61 y) received 110 DEB transarterial chemoembolization treatments over an 8-month study period. In 84.5% (93/110) of DEB transarterial chemoembolization procedures, the patients were discharged on the same day (group A). The causes of hospitalization included the worsening of comorbidities in 41.1% (7/17), pain control in 29.4% (5/17), and groin and closure device–related complications in 29.4% (5/17) of patients. The mean Charlson comorbidity scores in groups A and B were 6.96 (standard deviation [SD] ± 1.98) and 8.47 (SD ± 2.18) (P = .0005), respectively. All of the patients in group B had Barcelona Clinic Liver Cancer (BCLC) stages C and D HCC (P = .024). There were no Common Terminology Criteria for Adverse Events (CTCAE) grade III or worse adverse events (AEs). There was no mortality or emergency visits within 30 days of discharge. ConclusionsSame-day discharge after superselective DEB transarterial chemoembolization for unresectable HCC is safe and feasible. BCLC C or D stage of disease, a higher Charlson comorbidity score, and groin or closure device complications are correlated with a greater likelihood for overnight admission.

Current Status of Hepatocellular Carcinoma Treatment in Japan

Transarterial chemoembolization (TACE) is the gold standard of treatment for intermediate-stage hepatocellular carcinoma (HCC), and involves the administration of cytotoxic drugs, with or without lipiodol, by means of a catheter directly to the hepatic artery followed by the administration of embolizing agents such as spherical gelatin or polyvinyl alcohol particles. There are currently no global guidelines regarding the dose, choice or combination of cytotoxic agents for TACE; therefore it is difficult to compare data from different TACE studies. Superselective TACE with lipiodol is the primary TACE procedure that offers satisfactory levels of local control with a lower risk of complications. Approximately 40–70% of patients with HCC with tumours sized 4–5 cm or less attained complete tumour necrosis or remained local recurrence free for 3 years or longer following TACE. The early identification of unresponsiveness to TACE is important to allow for a timely switch to alternative therapies. The use of novel embolizing materials in TACE such as drug-eluting beads and radioembolization is likely to have beneficial effects. Indeed, the increase in angiogenic activity following TACE emphasizes the potential of TACE in combination with targeted molecular therapies such as the anti-angiogenesis inhibitor, sorafenib.

Transarterial Chemoembolization Plus Sorafenib: A Sequential Therapeutic Scheme for HCV-Related Intermediate-Stage Hepatocellular Carcinoma: A Randomized Clinical Trial

Recurrence of hepatocellular carcinoma (HCC) is a major problem after surgical or ablative treatments. The aim of this prospective, single-center, placebo-controlled, randomized, double-blind clinical study was to evaluate the effectiveness of transarterial chemoembolization (TACE) combined with sorafenib as a sequential treatment regimen in delaying time to progression (TTP) of intermediate-stage HCC in patients with chronic hepatitis C virus (HCV) infection. Between October, 2007 and January, 2011, 80 HCV-infected patients with Barcelona Clinic Liver Cancer stage B HCC underwent the TACE procedure. All had Child-Pugh class A disease. They were randomized 1:1 to receive sorafenib at a dose of 400 mg twice daily or placebo. Endpoints were the TTP and the rates of adverse events and toxicity. Sixty-two of 80 patients (77%), 31 in the sorafenib group and 31 in the control group, completed the study. The median TTP was 9.2 months in the sorafenib group and 4.9 months in the placebo group (hazard ratio, 2.5; 95% confidence interval, 1.66-7.56; p < .001). Metachronous, multicentric HCC progression occurred less frequently in sorafenib-treated patients (p < .05). Adverse reactions to sorafenib caused withdrawal from the study of 9 (22%) patients. A conventional TACE procedure followed by sorafenib treatment resulted in a significantly longer TTP in patients with intermediate-stage HCV-related HCC, with no unexpected side effects.

Interventional Radiology in Oncology: Clinical Management of Patients Undergoing Transarterial Chemoembolization for Hepatic Malignancies

Interventional radiology procedures treat a variety of solid tumor malignancies. Transarterial chemoembolization (TACE) is a minimally invasive procedure performed under fluoroscopic guidance that is used in treatment of hepatic malignancies because of hepatocellular carcinoma or malignancy that has metastasized to the liver. Patients undergoing a TACE procedure may manifest postembolization symptoms such as fever, nausea, vomiting, and abdominal pain, which may persist after discharge. Patients need to be educated on the importance of compliance with prescribed medications, clinical symptoms to be expected, and signs of potential complications that need to be reported.

Perspectives on the Design of Clinical Trials Combining Transarterial Chemoembolization and Molecular Targeted Therapy

Transarterial chemoembolization (TACE) moderately prolongs the survival of patients with intermediate-stage hepatocellular carcinoma. Molecular targeted therapy (MTT) may improve the efficacy of TACE. However, the findings of clinical trials evaluating the efficacy of a combination of TACE and MTT are conflicting. We hypothesized that this disparity can be prevented using alternative study designs. In this review, we classify the pertinent issues of study designs into five domains: primary endpoints, patients, TACE procedures, timing of randomization, and drug administration. Furthermore, we discuss the methods for increasing the success rate by minimizing potentially confounding factors within these five domains. Transarterial chemoembolization (TACE) is the current standard therapy for patients with Barcelona Clinic Liver Cancer (BCLC) intermediate-stage hepatocellular carcinoma (HCC) [1–3]. The survival benefit of TACE is supported by the results of meta-analysis of clinical trials comparing TACE with other conservative treatments in patients with inoperable HCC [4]. The results showed that the median survival of patients improved from approximately 16 to 20 months following TACE [4, 5]. Although advances in TACE techniques and the use of new embolization agents may improve the efficacy of TACE [6, 7], other approaches are needed to further improve the outcome in HCC patients treated using TACE. Molecular targeted therapy (MTT) has improved the survival of patients with advanced-stage HCC [5, 8]. Therefore, combining MTT and TACE may additionally improve the survival in patients with intermediate-stage HCC. Many molecular targeted agents (MTA) are currently undergoing evaluation in randomized trials (table 1). However, the designs of these trials differ significantly. The results of two trials combining sorafenib and TACE were recently reported. Both trials failed to demonstrate a therapeutic benefit of the combination therapy for time to tumor progression (TTP) or overall survival (OS) [9, 10]. However, specific subgroups of patients who received treatment for more than 6 months exhibited significantly better survival (table 2). Because median survival can be greater than 2 years in patients with intermediate-stage HCC, it is likely that an extended exposure period is necessary for MTA effects to reach the biological threshold at which survival benefit becomes measurable. Therefore, early discontinuation of study drug treatment may significantly undermine the statistical power of efficacy analysis in randomized trials (fig. 1). Clinical trials should be designed to minimize confounding factors that could lead to early discontinuation of study drug [1–3, 11, 12]. Factors that are crucial in this regard can be categorized into five domains: (1) selection of primary endpoints, (2) selection of patient population, (3) selection of TACE procedures, (4) timing of randomization, and (5) study drug administration. In this review we discuss the confounding effects potentially associated with each domain and the possible interactions among domains in trials combining TACE and MTA. We also discuss strategies that can help improve sensitivity and accuracy measurements of MTA efficacy.

Value of 18-FDG-Positron Emission Tomography/Computed Tomography Before and After Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma Undergoing Liver Transplantation: Initial Results

IntroductionLiver transplantation is the treatment of choice for various types of end-stage liver disease and the most appropriate alternative for the treatment of hepatocellular carcinoma (HCC)-associated liver cirrhosis. The aim of this study was to describe our initial experience with the use of 18-FDG positron emission tomography (PET)/computed tomography CT before and after transarterial chemoembolization (TACE) in HCC patients undergoing liver transplantation, seeking to predict the percentage of tumor necrosis achieved by TACE procedures. Patients and MethodsFrom January 2007 through December 2009, 39 patients with HCC and liver cirrhosis were included in our liver transplantation program. We selected the 6 subjects who underwent 18-fluorodeoxyglucose PET/CT (18-FDG PET/CT) pre- and post-TACE. ResultsThe median SUV (standarized uptake value) in the lesions studied were 4 (range, 2.79–6.95) before TACE with a median post-TACE SUV of 0 (range, 0–4). Among patients whose post-TACE SUV decreased to <3, the percentage of necrosis after studying the hepatectomy was >80%. ConclusionPerformance of an 18-FDG PET/CT before and after TACE and comparison of SUV in patients with HCC awaiting liver transplantation provided valuable information regarding the effectiveness of TACE.

Transarterial Chemoembolization With Cisplatin as Second-Line Treatment for Hepatocellular Carcinoma Unresponsive to Chemoembolization With Epirubicin-Lipiodol Emulsion

The purpose of this retrospective study was to investigate the efficacy of transarterial chemoembolization (TACE) using cisplatin as a second-line treatment for advanced hepatocellular carcinoma (HCC) unresponsive to TACE using epirubicin-Lipiodol emulsion at our institution. Between January 2006 and March 2009, 51 patients with unresectable HCC underwent TACE using cisplatin. All patients had shown persistent viable tumor or tumor progression after at least 2 sessions of TACE using epirubicin-Lipiodol emulsion. TACE procedures consisted of arterial injection of a mixture of Lipiodol and cisplatin (30-100mg [mean 57±21]) (n=29) or arterial infusion of cisplatin (30-100mg [mean 87±19]) solution (n=22) followed by injection of 1-mm porous gelatin particles. Early tumor response was assessed by contrast-enhanced computed tomography (CT) according to Response Evaluation Criteria in Solid Tumors (RECIST) and European Association for the Study of the Liver (EASL) criteria. Overall survival and progression-free survival was calculated using the Kaplan-Meier method. Toxicity was assessed according to NCI-CTCAE version 3 criteria. Response rates were 11.8 and 27.5% by RECIST and EASL criteria, respectively. Overall survival rates were 61.9, 48.2, and 28.9% at 1, 2, and 3years, respectively, and the median survival time was 15.4months. Progression-free survival rate was 35.2% at 1year, and median progression-free survival time was 3.1months. No major complications were observed, and the occurrence of postembolization syndrome was minimal. Grade 3 to 4 toxicities included thrombocytopenia (5.8%), increased aspartate aminotransferase (AST) level (35.3%), and increased alanine aminotransferase (ALT) level (23.5%). Switching the TACE anticancer drug from epirubicin to cisplatin might be the feasible option for advanced HCC, even when considered resistant to the initial form of TACE.

Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma: Predictors of Survival

Transarterial chemoembolization (TACE) is the mainstay of management for patients with hepatocellular carcinoma who are not suitable for curative treatments. To determine factors associated with mortality after the first TACE procedure. From January 2004 to May 2008, 60 patients underwent TACE as treatment for hepatocellular carcinoma. Clinical and biochemical parameters before TACE, and response after TACE, were evaluated with conventional classifications (WHO, Response Evaluation Criteria in Solid Tumors [RECIST], and European Association for the Study of the Liver [EASL] criteria) and with one-, two- and three-dimensional assessment. Overall median survival after the first TACE procedure was 17.1±3.4 months. According to Cox regression analysis, having an alpha-fetoprotein level of greater than 200 ng⁄mL (HR 2.35 [P=0.02]) and a Model for End-stage Liver Disease (MELD) score of greater than 10 (HR 4.19 [P=0.001]) were associated with higher risk of mortality; whereas reduction in tumour size measured in one dimension (HR 0.96 [P=0.005]), two dimensions (HR 0.98 [P=0.004]) and three dimensions (HR 0.98 [P=0.001]) was associated with lower risk of mortality. Moreover, reduction in tumour size by 3% or more assessed in one, two or three dimensions was associated with lower risk of mortality (HR 0.48 [P=0.04]; HR 0.36 [P=0.01]; HR 0.31 [P=0.003], respectively). The three conventional classifications were not useful for predicting mortality (WHO: HR 1.07 [P=0.9]; RECIST: HR 0.94 [P=0.9]; EASL: HR 0.94 [P=0.9]). Having an alpha-fetoprotein level of greater than 200 ng⁄mL and a MELD score of greater than 10 before undergoing TACE was associated with a greater risk of mortality. Conventional classifications of response were not useful for predicting mortality. Reduction in tumour size after the first TACE procedure was associated with better survival, primarily if patients had more than a 3% reduction in tumour size assessed by three-dimensional measurement.

Semiautomated Segmentation for Volumetric Analysis of Intratumoral Ethiodol Uptake and Subsequent Tumor Necrosis After Chemoembolization

Linear measurements, such as those described by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, may be limited for assessment of response after transarterial chemoembolization (TACE). The purpose of this pilot study was to show intra- and interobserver reproducibility of volumetric measurements of Ethiodol (ethiodized oil) seen within tumor 24 hours after TACE and of necrotic and viable tumor 1 month after treatment. Volumetric measurements are compared with linear measurements and survival outcomes. Between 2006 and 2009, 37 consecutive TACE procedures were performed in 27 patients with hepatic malignancies. CT images obtained 24 hours and 1 month after TACE were retrospectively analyzed. Three observers measured volumes twice. Intraoperator reproducibility was determined using Wilcoxon's signed rank test to assess whether the difference in each volumetric measurement approaches zero. The intraclass correlation coefficient (ICC) and Bland-Altman plots were used to determine interoperator reproducibility. Survival data were retrospectively obtained from the electronic medical record. Good intraobserver reproducibility and interobserver reproducibility (p > 0.05, ICC > 0.9, respectively) were shown for Ethiodol, whole tumor, and necrotic tumor volumes. The volume of Ethiodol correlated with subsequent necrotic tumor volume (p = 0.009), reduction in whole tumor volume (p = 0.004), and patient survival (p = 0.029). Kaplan-Meier curves suggest that Ethiodol accumulation in more than 50% of the tumor and a 10% or greater increase in the volume of necrotic tumor correlated with survival (p = 0.028 and 0.047, respectively). Semiautomated volumetric analysis can be performed with good intra- and interobserver reproducibility. The volume of Ethiodol accumulated in the tumor after TACE correlates with subsequent necrosis. These early measurements may predict survival outcomes.

Acute Ischemic Cholecystitis After Transarterial Chemoembolization of Hepatocellular Carcinoma

To determine the incidence and clinical outcome of acute ischemic cholecystitis after transarterial chemoembolization (TACE) of hepatocellular carcinoma. In this ethics board-approved study, a retrospective review of 355 TACE procedures performed in 246 patients during a 5-year period was performed. The review of postintervention computed tomography (CT) reports for findings indicative of acute cholecystitis identified 12 patients (4.9%). In these patients, all CT scans, laboratory results (white blood cell count, alkaline phosphatase level, total bilirubin level), and clinical reports were analyzed to assess imaging findings and outcomes at the following time points: before TACE, within the first week after the procedure, as well as 1 and 6 months post-TACE. In 11 of 12 cases, the dominant finding on CT was new gallbladder wall thickening of up to 12 mm, which developed within 24 hours in 10 patients and within the first month after TACE in 1 patient. Gallbladder wall thickening persisted in 1 patient for at least 6 months. Eleven of 12 patients showed deposition of Lipiodol in the gallbladder wall. In 1 patient, the dominant finding on CT was pericholecystic stranding that resolved on follow-up CT after 1 month. None of the patients demonstrated gas in the gallbladder wall, significant pericholecystic fluid, abdominal or liver abscesses. Blood work results revealed transient increase in white blood cell count, alkaline phosphatase level, and total bilirubin level, not different from that seen after TACE in patients without CT evidence of cholecystitis. Clinical reports documented transient right upper quadrant pain for a few days and up to 1 month in 1 case with eventual symptom relief. None of the cases required surgical or radiological intervention. All but 1 case demonstrated normal gallbladder wall thickness after 6 months. Acute ischemic cholecystitis is not an uncommon complication after TACE. However, it is self-limiting and does not seem to require any intervention or surgery.

Abstract No. 286: Biliary complications after transarterial chemoembolization for hepatocellular carcinoma

Given the range of techniques and chemoembolic formulations currently in use, the prevalence and risk factors for biliary injury following transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) remain unclear. The purpose of this study is to determine the prevalence of biliary complications following three-drug and gelfoam TACE. Records of 122 consecutive patients (mean age 61 years; 96 men) who underwent TACE (1-8 treatments per patient) for HCC in 2008 were retrospectively reviewed. Segmental or subsegmental TACE using a mixture of doxorubicin 25 mg, cisplatin 50 mg and mitomycin C 10 mg with Ethiodol followed by gelfoam slurry was performed. All patients completed follow-up liver function tests and a contrast-enhanced CT of the abdomen four weeks after TACE. Biliary complications including intrahepatic biliary ductal dilation, biloma or biliary sepsis were encountered in 12 patients (10%). Four of the patients developed cholangitis which required hospital admission, and one presented with a liver abscess which was treated with intravenous antibiotics. The remaining seven (58%) were asymptomatic with new segmental or lobar intrahepatic biliary ductal dilation noted on routine followup CT. Patients with a biliary complication had undergone a higher number of TACE procedures (3.2 versus 2.3; p=0.05). Biliary complications after TACE may be more prevalent in current practice than previously described in the literature.

Transarterial chemoembolization as initial treatment for unresectable hepatocellular carcinoma in southern China

To identify prognostic factors from pretreatment variables of the initial transarterial chemoembolization (TACE) procedure in unresectable hepatocellular carcinoma (HCC). One thousand and five hundred and sixty-nine patients with unresectable HCC underwent TACE as initial treatment were retrospectively studied. Pretreatment variables of the initial TACE procedure with a P value less than 0.05 by univariate analysis were subjected to Cox proportional hazards model. The median overall survival time and 1-, 5-, 10-year survival rates were 10.37 mo, 47%, 10%, and 7%, respectively. A Cox proportional hazard model showed that 8 pretreatment factors of regional lymph nodes metastasis, Child-Pugh class, macrovascular invasion, greatest dimension, alpha-fetoprotein (AFP), Hepatitis virus B, tumor capsule, and nodules were independent prognostic factors. Patients with multimodality therapy have better survival than those with TACE treatment only. Tumor status, hepatic function reserve, AFP, and hepatitis virus B status were independent prognostic factors for unresectable HCC. Distant metastasis might not be a contraindication to TACE. Multimodality therapy might improve survival.

Clinical Factors Associated with Dense and Wedge-Shaped Nephrograms Detected 24 h After Chemoembolization

This investigation aimed to evaluate patient characteristics and procedural factors associated with abnormal nephrograms encountered on noncontrast computed axial tomography (CAT) obtained 24-h after transarterial chemoembolization (TACE) for primary and metastatic hepatic malignancies. Sixty hepatic chemoembolization procedures were performed in 29 patients who had a median age of 63 years (range 42–79). The male-to-female ratio was 16:13. Noncontrast CAT scans were obtained approximately 24 h after TACE as part of our institutional protocol and were examined for persistent renal nephrograms. These findings were compared with clinical and procedural parameters to determine whether there was any association with these factors or with the occurrence of acute renal failure (ARF). Abnormally persistent CAT nephrograms were observed 24 h after 28 of 60 (46.7%) TACE procedures, of which 14 (23.3%) were persistent, bilaterally dense, global nephrograms, and 14 (23.3%) were small, wedge-shaped, and focal nephrograms. The change in serum creatinine from baseline to 24 h was significantly greater (p = 0.031) in the global nephrogram group. The presence of cirrhosis, Child-Pugh score, procedure time, baseline renal insufficiency, and lower periprocedural mean arterial blood pressure were also statistically significantly associated with the occurrence of bilateral globally dense nephrograms. The procedure time was statistically significantly associated with the occurrence of wedge-like focally persistent nephrograms. Global, persistently dense nephrograms and wedge-shaped focally persistent nephrograms are not infrequently observed after TACE. Persistent global nephrograms can be an important clinical indicator of ARF. The wedge nephrogram may represent focal renal ischemia.

Pilot Study of Transarterial Chemoembolization With Pirarubicin and Amiodarone for Unresectable Hepatocellular Carcinoma

Further to a previous study whereby we reported that an in vitro emulsion of pirarubicin, amiodarone, and lipiodol was more stable and cytotoxic than a classic doxorubicin-lipiodol mixture, we designed a pilot study to evaluate efficacy and toxicity of a transarterial chemoembolization (TACE) procedure using a combination of pirarubicin, amiodarone, lipiodol, and gelatin sponge. The 43 patients included in this study underwent TACE for unresectable hepatocellular carcinoma. Computed tomography scans were performed to assess tumor response (RECIST) and lipiodol uptake after the first session. Median follow-up lasted 30 months. Endpoints were overall and progression-free survival. Survival was estimated using Kaplan Meier estimations and compared using log-rank tests. Univariate and multivariate Cox analyses were used to calculate hazard ratios with their 95% confidence interval (CI). Twenty-seven (67.5%) patients had alcoholic cirrhosis. Mean tumor size was 9.5 cm (1-20 cm) and 37/43 were multifocal or diffuse. Cancer of the liver Italian program score was 0 in 7/40 and 1 in 16/40. Mean number of TACE sessions was 3.5 (1-11). There were 3 treatment-related deaths (2 severe sepsis, 1 bowel perforation). A partial response and a stable disease were observed in 12 (28%) and 29 (67%) patients, respectively. Median overall and progression-free survivals were 29 months (95% CI: 13.8-45) and 15 months (95% CI: 11.5-20.8), respectively. Cancer of the liver Italian program score <or=1 (P = 0.042) and lipiodol uptake >25% (P = 0.003) were independent prognostic factors for better overall survival. This new TACE procedure is safe with a high overall survival rate and certainly deserves phase III investigation to compare it with classic treatments such as doxorubicin-lipiodol TACE.

Transarterial chemoembolization (TACE) of liver metastases (LM) from colorectal carcinoma (CRC) adopting drug eluting beads preloaded with irinotecan (DEBIRI): Results of a phase II study on 82 patients

4092 Background: DC beads are new embolic microspheres capable to load IRI. The present phase II study investigated response and side effects after TACE adopting DEBIRI in 82 patients with LM from CRC not resectable and in progression after two lines of chemtherapy. Methods: A total of 185 TACE procedures were performed. A suspension of polyvinyl-alcohol beads (DC Bead) preloaded with Irinotecan ( 81 TACE procedures with 2ml of microspheres preloaded with 100mgr of Irinotecan and 104 with 4ml loaded with 200mgr of Irinotecan) was delivered selectively into hepatic arteries. All pts received a well defined prophylactic treatment against nausea and vomiting, infections, and upper quadrant right pain (UQRP).Tropisetron, hydration, antibiotics, morphine and intra-arterial lidocaine was delivered as reported in previous experiences ( ASCO GI abs 356,2007; IN VIVO. 21, 6, 2007). Follow-up studies were performed by contrast enhanced spiral multislice computed tomography (MsCT) 1 month after the procedures and every 3 months or when clinically required. Quality of life (QoL) was assessed by Edmonton SAS improvement scale before, after TACE and then monthly. Results: We obtained 100% technical success in TACEs performed, and no complications due to the procedure occurred. Patients developed a postembolization-syndrome with the following side effects : UQRP (G2), fever (G2), nausea (G2) and increased transaminases (G2–3) in 40%,80%,80%,70% respectively out of 185 procedures done. One pt presented acute pancreatitis. The median follow-up was 18.2 months. Within 1 month after treatment, CT scan showed significant ( 75–100%) reduction of metastatic contrast enhancement in all lesions treated. Therapeutic response (according to RECIST was observed in 78% of patients. After TACE. 75 out 82 pts (90%) declare a general improvement of QoL long lasting. Conclusions: We suggest that TACE with DEBIRI could be a palliative therapy for LM from CRC. Our promising experience need to be confirmed with further phase III studies. Mid and long-term results need to be carefully evaluated comparing them with systemic chemotherapy. No significant financial relationships to disclose.

Selective internal radiation therapy (SIRT) as salvage therapy for uveal melanoma (UM) hepatic metastases

9066 Background: The liver is the first site of metastasis in &gt;80% of patients with UM. Transarterial chemoembolization (TACE) has been used to control hepatic metastases, however, patients eventually progress through or experience complications related to TACE. We report our results using SIRT as salvage therapy for patients with UM liver metastases who are no longer candidates for TACE. Methods: Patients with UM liver metastases previously treated with TACE were treated with SIRT. Patients were followed 1-month post-SIRT for acute toxicity then every 3 months for tumor response evaluation and for complications of delayed toxicity. Common Toxicity Criteria 3.0 (CTC) was used for toxicity assessment. Best radiographic tumor response was determined by MRI using RECIST criteria. Results: Five men and 7 women, ages 48–81 (median 65) with UM liver metastases were treated with SIRT after tumor progression post-TACE (n=9), complications of TACE (n=1) or patient preference (n=2). Pretreatment whole liver tumor burdens were as follows: &lt;25% (n=10), 25–50% (n=1) and &gt;50% (n=1). Patients had both hepatic lobes treated on separate occasions (n=7), one lobe (n=3) or whole liver (n=2) therapy. Treatment dose per patient was reduced by 25% due to prior TACE procedures. The mean total SIRT dose delivered was 1.0 GBq (0.62–1.47 GBq). Five patients had an increase in hepatic enzymes (Grade 1–4) at 1-month follow-up. No procedure related deaths or serious adverse events were experienced. Best tumor response was as follows: CR (n=0), PR (n=0), SD (n=8), PD (n=4), with a median follow-up of 7.8 months (1.0–16.0). The median time to liver progression was 7.0 months (1.0- 15.5). Nine of the 12 patients, including 2 patients with &gt;25% pretreatment tumor burden, died due to progression of liver disease (n=6), extrahepatic disease (n=1) or both (n=2). Post-SIRT, median overall patient survival was 10.8 months (1.0–19.0). Three patients (ECOG 0 performance status) are still alive at 13.5–19.0 months (median 16.2 months) following SIRT. Conclusions: SIRT was safely used and showed a potential clinical benefit for patients previously treated with TACE. Further investigation is warranted to determine if SIRT should be employed as a first line therapy for patients with UM liver metastases. No significant financial relationships to disclose.

Rupture and intra-peritoneal bleeding of a hepatocellular carcinoma after a transarterial chemoembolization procedure: a case report

BackgroundTransarterial chemoembolization (TACE) is a well accepted treatment for inoperable hepatocellular carcinoma (HCC). While minor complications involve 10% of all patients, severe complications are rare.Case PresentationWe describe a case of a 90-year-old male with a large, superficial HCC who underwent TACE. He had a significant intraperitoneal bleed secondary to tumor rupture immediately following the procedure.ConclusionTumor size and superficial location must be considered risk factors for tumor rupture and related complications.