Improving pain control during transarterial chemoembolization for hepatocellular carcinoma performed under local anesthesia with multimodal analgesia.

PURPOSE: The purpose of this study was to assess the performance of a reinforced analgesic protocol (RAP) on pain control in patients undergoing conventional trans-arterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Eighty-one consecutive patients (57 men, 24 women) with a mean age of 69 ± 10 (standard deviation) years (age range: 49-92 years) underwent 103 cTACEs. Standard antalgic protocol (50 mg hydroxyzine, 10 mg oxycodone, 8 mg ondansetron, and lidocaine for local anesthesia) was prospectively compared to a RAP (standard + 40 mg 2-h infusion nefopam and 50 mg tramadol). The individual pain risk was stratified based on age, the presence of cirrhosis and alcoholic liver disease, and patients were assigned to a low-risk group (standard protocol) or high-risk group (RAP). The primary endpoint was severe periprocedural abdominal pain (SAP), defined as a visual analog scale score ≥30/100. A predefined intermediate analysis was performed to monitor the benefit-risk of the RAP. Based on the intermediate analysis, all patients were treated with the RAP. RESULTS: The intermediate analysis performed after 52 cTACE showed that 2/17 (12%) high-risk patients (i.e., those receiving the RAP) experienced SAP compared to 15/35 (43%) low-risk patients (odds ratio [OR] = 0.18; 95% confidence interval [CI]: 0.02-0.98; P = 0.03). Analysis of all procedures showed that 12/67 (18%) patients in cTACE receiving the RAP experienced SAP compared to 15/36 (42%) patients who did not receive it (OR = 3.27; 95% CI: 1.32-8.14; P = 0.01). There were no statistical differences in adverse events, particularly for nausea, between groups. CONCLUSION: Reinforcing the analgesic protocol by combining non-opioid and opioid molecules reduces perioperative pain in patients undergoing cTACE for HCC.

Summary of key guidelines for locoregional treatment of HCC in Asia, Europe, South and North America.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide accounting for over 800,000 new cases in 2018, with the highest incidence in Asia and Africa where hepatitis B is the most common risk factor. In Europe, Japan, and the United States, hepatitis C chronic alcohol abuse and non-alcoholic fatty liver disease are more common risk factors. Five-year survival is low, less than 20% worldwide. HCC is a particularly challenging disease to treat because therapeutic options and prognosis must also consider hepatitis or cirrhosis independent of the malignancy. Locoregional therapies (LRT) including ablation, arterially directed therapy and external beam radiation are the preferred treatments for patients with good performance status, unresectable disease limited to the liver and preserved liver function. In practice, patients with portal vein tumor thrombus and limited extrahepatic disease may also be considered candidates for LRT. There are several guidelines developed by expert panels provide recommendations on treating this challenging disease including the Barcelona Clinic Liver Cancer, European Association for the Study of the Liver, European Society for Medical Oncology, American Association for the Study of the Liver Diseases, and the National Comprehensive Cancer Network. The purpose of this paper is to review the guidelines as they are applied clinically in regions with high incidence of HCC.

Health-related quality of life in locally advanced hepatocellular carcinoma treated by either radioembolisation or sorafenib (SARAH trial).

BACKGROUND: The aim of this ancillary study of the SARAH trial is to compare health-related quality of life (HRQoL) in patients with locally advanced or inoperable hepatocellular carcinoma (HCC) treated with transarterial radioembolisation (TARE) or sorafenib. METHODS: This study included randomised patients who received either TARE or at least one dose of sorafenib with no major deviation in the protocol and who had at least one QoL follow-up assessment in addition to the baseline evaluation. QoL was assessed from the date of randomisation using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire, until disease progression or other reasons for stopping study participation. Data were analysed using linear mixed and time-dependent models. RESULTS: A total of 285 patients were included (122 and 163, in the TARE and sorafenib groups, respectively). Questionnaire completion rates were similar (77.5% versus 80.4%, in the TARE and sorafenib groups, respectively, p = 0.25). Longitudinal HRQoL analysis showed a significant treatment and time effects for fatigue and global health status, and significant treatment, time and treatment by time interaction effects for appetite loss, diarrhoea and social functioning. The median time to deterioration for the global health status was 3.9 months (95% confidence interval [CI] 3.7-4.3) versus 2.6 months (95% CI 2.0-3.0) in the TARE and sorafenib groups, respectively. CONCLUSIONS: HRQoL was preserved longer with TARE than with sorafenib in locally advanced HCC. These data could be used to optimise management of patients with advanced or inoperable HCC.

NEMESIS: Noninferiority, Individual-Patient Metaanalysis of Selective Internal Radiation Therapy with 90Y Resin Microspheres Versus Sorafenib in Advanced Hepatocellular Carcinoma.

In randomized clinical trials, no survival benefit has been observed for selective internal radiation therapy (SIRT) over sorafenib in patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess, through a metaanalysis, whether overall survival (OS) with SIRT, as monotherapy or followed by sorafenib, is noninferior to sorafenib and to compare safety profiles for patients with advanced HCC. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library up to February 2019 to identify randomized clinical trials comparing SIRT, as monotherapy or followed by sorafenib, with sorafenib monotherapy among patients with advanced HCC. The main outcomes were OS and frequency of treatment-related severe adverse events (≥grade 3). The per-protocol population was the primary analysis population. A noninferiority margin of 1.08 in terms of hazard ratio was prespecified for the upper boundary of 95% confidence interval for OS. Prespecified subgroup analyses were performed. Results: Three randomized clinical trials, involving 1,243 patients, comparing sorafenib with SIRT (SIRveNIB and SARAH) or SIRT followed by sorafenib (SORAMIC), were included. After randomization, 411 of 635 (64.7%) patients allocated to SIRT and 522 of 608 (85.8%) allocated to sorafenib completed the studies without major protocol deviations. Median OS with SIRT, whether or not followed by sorafenib, was noninferior to sorafenib (10.2 and 9.2 mo [hazard ratio, 0.91; 95% confidence interval, 0.78-1.05]). Treatment-related severe adverse events were reported in 149 of 515 patients (28.9%) who received SIRT and 249 of 575 (43.3%) who received sorafenib only (P < 0.01). Conclusion: SIRT as initial therapy for advanced HCC is noninferior to sorafenib in terms of OS and offers a better safety profile.

Tumor burden and liver function in HCC patient selection for selective internal radiation therapy: SARAH post-hoc study.

Aim: To determine whether a liver tumor burden ≤25% and well-preserved liver function (albumin-bilirubin grade 1) are appropriate criteria for identifying patients with unresectable hepatocellular carcinoma who may benefit from selective internal radiation therapy (SIRT) using 90yttrium resin microspheres versus sorafenib. Patients & methods: Post-hoc analysis of patients in the intention-to-treat population of the SARAH trial (SIRT vs sorafenib) with ≤25% tumor burden and albumin-bilirubin grade 1. Primary end point: overall survival. Results: Median overall survival was 21.9 months (95% CI: 15.2-32.5, n = 37) with SIRT and 17.0 months (11.6-20.8, n = 48) with sorafenib (hazard ratios: 0.73; 95% CI: 0.44-1.21; p = 0.22). Conclusion: A combination of good liver function and low tumor burden may be relevant for selection of hepatocellular carcinoma patients for SIRT.

Lipiodol retention pattern after TACE for HCC is a predictor for local progression in lesions with complete response.

BACKGROUND: To evaluate the predictive value of the lipiodol retention pattern for local progression of HCC with a complete response (CR) on CT according to mRECIST criteria after a first session of conventional chemoembolization (cTACE). METHODS: From January 2014 to May 2016 all consecutive patients undergoing a first cTACE session for HCC were identified. Inclusion criteria were the presence of ≤3 HCCs and available pre- and post-cTACE CT. Tumor response was classified according to mRECIST criteria. The analysis focused on tumors with a CR. The lipiodol retention pattern in these tumors was classified as complete (C-Lip, covering the entire tumor volume), or incomplete (I-Lip). Local progression was defined as the reappearance of areas of enhancement on arterial-phase images with washout on portal/delayed phase images within 2 cm from treated tumors on follow-up CT. RESULTS: The final population included 50 patients with 82 HCCs. A total of 46 (56%) HCCs were classified with a CR, including 16 (35%) with I-Lip, and 30 (65%) with C-Lip. After a median follow-up of 14 months (3.2-35.9 months), 15/16 (94%) and 10/30 (30%) of I-Lip and C-Lip HCCs showed local progression on CT, respectively (p < 0.001), with no significant difference in the time to progression (mean 11.1 ± 2 vs. 13.4 ± 3 months for I-Lip and C-Lip, respectively p = 0.51). CONCLUSIONS: HCCs with incomplete lipiodol retention after a first cTACE session have a high risk of local progression even when there is a CR according to mRECIST, and should be considered to be incompletely treated.

Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial.

BACKGROUND: Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma. We aimed to compare the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 (90Y) resin microspheres in patients with hepatocellular carcinoma. METHODS: SARAH was a multicentre, open-label, randomised, controlled, investigator-initiated, phase 3 trial done at 25 centres specialising in liver diseases in France. Patients were eligible if they were aged at least 18 years with a life expectancy greater than 3 months, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, Child-Pugh liver function class A or B score of 7 or lower, and locally advanced hepatocellular carcinoma (Barcelona Clinic Liver Cancer [BCLC] stage C), or new hepatocellular carcinoma not eligible for surgical resection, liver transplantation, or thermal ablation after a previously cured hepatocellular carcinoma (cured by surgery or thermoablative therapy), or hepatocellular carcinoma with two unsuccessful rounds of transarterial chemoembolisation. Patients were randomly assigned (1:1) by a permutated block method with block sizes two and four to receive continuous oral sorafenib (400 mg twice daily) or SIRT with 90Y-loaded resin microspheres 2-5 weeks after randomisation. Patients were stratified according to randomising centre, ECOG performance status, previous transarterial chemoembolisation, and presence of macroscopic vascular invasion. The primary endpoint was overall survival. Analyses were done on the intention-to-treat population; safety was assessed in all patients who received at least one dose of sorafenib or underwent at least one of the SIRT work-up exams. This study has been completed and the final results are reported here. The trial is registered with ClinicalTrials.gov, number NCT01482442. FINDINGS: Between Dec 5, 2011, and March 12, 2015, 467 patients were randomly assigned; after eight patients withdrew consent, 237 were assigned to SIRT and 222 to sorafenib. In the SIRT group, 53 (22%) of 237 patients did not receive SIRT; 26 (49%) of these 53 patients were treated with sorafenib. Median follow-up was 27·9 months (IQR 21·9-33·6) in the SIRT group and 28·1 months (20·0-35·3) in the sorafenib group. Median overall survival was 8·0 months (95% CI 6·7-9·9) in the SIRT group versus 9·9 months (8·7-11·4) in the sorafenib group (hazard ratio 1·15 [95% CI 0·94-1·41] for SIRT vs sorafenib; p=0·18). In the safety population, at least one serious adverse event was reported in 174 (77%) of 226 patients in the SIRT group and in 176 (82%) of 216 in the sorafenib group. The most frequent grade 3 or worse treatment-related adverse events were fatigue (20 [9%] vs 41 [19%]), liver dysfunction (25 [11%] vs 27 [13%]), increased laboratory liver values (20 [9%] vs 16 [7%]), haematological abnormalities (23 [10%] vs 30 [14%]), diarrhoea (three [1%] vs 30 [14%]), abdominal pain (six [3%] vs 14 [6%]), increased creatinine (four [2%] vs 12 [6%]), and hand-foot skin reaction (one [<1%] vs 12 [6%]). 19 deaths in the SIRT group and 12 in the sorafenib group were deemed to be treatment related. INTERPRETATION: In patients with locally advanced or intermediate-stage hepatocellular carcinoma after unsuccessful transarterial chemoembolisation, overall survival did not significantly differ between the two groups. Quality of life and tolerance might help when choosing between the two treatments. FUNDING: Sirtex Medical Inc.

Imaging review of hepatocellular carcinoma after thermal ablation: The good, the bad, and the ugly.

Image-guided thermal ablation is a well-established locoregional technique for the treatment of hepatocellular carcinoma (HCC). HCC surveillance programs have led to an increase in the number of patients diagnosed at an early stage of the disease who are eligible for thermal ablation. Tumor response is assessed on imaging and requires extensive follow-up; thus, radiologists play a key role in defining the technical success and efficacy of treatment as well as identifying progressive disease. Although they are rare, complications, such as secondary infections, must also be identified. Several contrast-enhanced imaging techniques can be used at different postprocedural timepoints but magnetic resonance imaging (MRI) and computed tomography (CT), which allow both liver-centered and whole-body imaging are the cornerstones of follow-up. This review describes the imaging features of HCC following thermal ablation. After describing the basic technical elements of follow-up imaging, imaging findings are divided into three groups: normal and expected features (the good), abnormal features, uncontrolled disease, and complications (the bad), and atypical or rare presentations (the ugly). J. Magn. Reson. Imaging 2016;44:1070-1090.

Correlation of tumor response on computed tomography with pathological necrosis in hepatocellular carcinoma treated by chemoembolization before liver transplantation.

The purpose of this article was to compare the results of Response Evaluation Criteria in Solid Tumors (RECIST), modified Response Evaluation Criteria in Solid Tumors (mRECIST), and European Association for the Study of the Liver (EASL) criteria for the evaluation of tumor necrosis in patients treated with transarterial chemoembolization before liver transplantation (LT) for hepatocellular carcinoma. Response to treatment was evaluated on computed tomography scan by 2 independent readers based on RECIST, mRECIST, and EASL criteria, and compared with tumor necrosis assessed by explant pathology. Necrosis was defined as major when >90%. Factors associated with major necrosis were tested by multivariate analysis. Fifty-eight patients (53 males; mean age, 54 years; range, 31-64 years) were included with 88 nodules. Fifty-one (58%) nodules were shown to have major necrosis. Among them readers 1 and 2 identified a complete response (CR) according to RECIST, mRECIST, and EASL criteria in 2 (4%), 47 (92%), and 47 (92%), and 1 (2%), 45 (88%), and 45 (88%) nodules, respectively. However, 12-14 of 59 nodules classified as CR on mRECIST or EASL criteria were found to have intermediate or minor necrosis (overestimation in 20%-24% of the patients). Combining the classification of CR by mRECIST and EASL criteria and complete lipiodol deposition reduced the overestimation to 11%. Among 59 nodules classified with a CR according to mRECIST or EASL, those with complete lipiodol deposition (n = 36, 61%) had a higher rate of necrosis than those with incomplete lipiodol deposition (n = 23, 39%): 95% versus 68% and 95% versus 63% for reader 1 and 2, respectively. In conclusion, CR based on mRECIST/EASL combined with complete lipiodol deposition was better for identification of major tumor necrosis. Even in the presence of CR according to mRECIST/EASL, incomplete lipiodol deposition should be considered indicative of substantial viable tumor remnant. Liver Transplantation 22 1491-1500 2016 AASLD.

Radioembolisation with yttrium‒90 microspheres versus sorafenib for treatment of advanced hepatocellular carcinoma (SARAH): study protocol for a randomised controlled trial.

BACKGROUND: Untreated advanced hepatocellular carcinoma (HCC) is linked to poor prognosis. While sorafenib is the current recommended treatment for advanced HCC, radioembolisation (RE; also called selective internal radiation therapy or SIRT) with yttrium-90 microspheres has shown efficacy in cohort studies. However, there are no head-to-head trials comparing radiation therapy with yttrium-90 microspheres and sorafenib in advanced HCC. The SARAH trial has been designed to compare the efficacy and safety of sorafenib therapy and RE using yttrium-90 resin microspheres (SIR-Spheres™; Sirtex Medical Limited, North Sydney, Australia) in patients with advanced HCC. Quality of life (QoL) and cost-effectiveness will also be compared between therapies. METHODS/DESIGN: SARAH is a prospective, randomised, controlled, open-label, multicentre trial comparing the efficacy of RE with sorafenib in the treatment of patients with advanced HCC. The trial aims to recruit adults with a life expectancy of >3 months, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1, and: advanced HCC according to the Barcelona criteria (stage C) or recurrent HCC after surgical or thermoablative treatment who are not eligible for surgical resection, liver transplantation or thermal ablation; or two rounds of failed chemoembolisation. Patients will be randomised 1:1 to receive either RE or sorafenib 400 mg twice daily. All patients will be monitored for between 12 and 48 months following start of treatment. The primary endpoint of the SARAH trial is overall survival (OS). Secondary endpoints include: adverse events, progression-free survival at 6 months; tumour response rate; general or liver disease-specific QoL scores; and cost of each treatment strategy. Assuming an increase in median OS of 4 months with RE versus sorafenib therapy, randomising at least 400 patients (200 in each treatment arm) will be sufficient for 80% power and a bilateral alpha risk of 5%; therefore, 440 patients will be enrolled to allow for 10% loss of patients due to ineligibility. DISCUSSION: The SARAH trial is the first randomised head-to-head study to compare RE with sorafenib in advanced HCC, and will establish the potential role of RE in HCC treatment guidelines. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01482442, first received 28 November 2011.

Quantification of the triglyceride fatty acid composition with 3.0 T MRI.

The aim of this work was to validate a sequential method for quantifying the triglyceride fatty acid composition with 3.0 T MRI. The image acquisition was performed with a 3D spoiled gradient multiple echo sequence. A specific phase correction algorithm was implemented to correct the native phase images for wrap, zero- and first-order phase and rebuild the real part images. Then, using a model of a fat (1)H MR spectrum integrating nine components, the number of double bonds (ndb) and the number of methylene-interrupted double bonds (nmidb) were derived. The chain length (CL) was obtained from these parameters using heuristic approximation. Validations were performed on different vegetable oils whose theoretical fatty acid composition was used as reference and in five human subjects. In vivo measurements were made in the liver and in the subcutaneous and visceral adipose tissues. Linear regressions showed strong correlations between ndb and nmidb quantified with MRI and the theoretical values calculated using oil composition. Mean ndb/nmidb/CL were 1.80 ± 0.25/0.51 ± 0.21/17.43 ± 0.07, 2.72 ± 0.31/0.94 ± 0.16/17.47 ± 0.08 and 2.53 ± 0.21/0.84 ± 0.14/17.43 ± 0.07 in the liver, subcutaneous and visceral adipose tissues respectively. The results suggest that the triglyceride fatty acid composition can be assessed in human fatty liver and adipose tissues with a clinically relevant MRI method at 3.0 T.

Validation of dynamic contrast-enhanced ultrasound in predicting outcomes of antiangiogenic therapy for solid tumors: the French multicenter support for innovative and expensive techniques study.

OBJECTIVES: Dynamic contrast-enhanced ultrasound (DCE-US) has been used in single-center studies to evaluate tumor response to antiangiogenic treatments: the change of area under the perfusion curve (AUC), a criterion linked to blood volume, was consistently correlated with the Response Evaluation Criteria in Solid Tumors response. The main objective here was to do a multicentric validation of the use of DCE-US to evaluate tumor response in different solid tumor types treated by several antiangiogenic agents. A secondary objective was to evaluate the costs of the procedure. MATERIALS AND METHODS: This prospective study included patients from 2007 to 2010 in 19 centers (8 teaching hospitals and 11 comprehensive cancer centers). All patients treated with antiangiogenic therapy were eligible. Dynamic contrast-enhanced ultrasound examinations were performed at baseline as well as on days 7, 15, 30, and 60. For each examination, a perfusion curve was recorded during 3 minutes after injection of a contrast agent. Change from baseline at each time point was estimated for each of 7 fitted criteria. The main end point was freedom from progression (FFP). Criterion/time-point combinations with the strongest correlation with FFP were analyzed further to estimate an optimal cutoff point. RESULTS: A total of 1968 DCE-US examinations in 539 patients were analyzed. The median follow-up was 1.65 years. Variations from baseline were significant at day 30 for several criteria, with AUC having the most significant association with FFP (P = 0.00002). Patients with a greater than 40% decrease in AUC at day 30 had better FFP (P = 0.005) and overall survival (P = 0.05). The mean cost of each DCE-US was 180&OV0556;, which corresponds to $250 using the current exchange rate. CONCLUSIONS: Dynamic contrast-enhanced ultrasound is a new functional imaging technique that provides a validated criterion, namely, the change of AUC from baseline to day 30, which is predictive of tumor progression in a large multicenter cohort. Because of its low cost, it should be considered in the routine evaluation of solid tumors treated with antiangiogenic therapy.

Alternative Response Criteria (Choi, European association for the study of the liver, and modified Response Evaluation Criteria in Solid Tumors [RECIST]) Versus RECIST 1.1 in patients with advanced hepatocellular carcinoma treated with sorafenib.

INTRODUCTION: Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), may underestimate activity and does not predict survival in patients with hepatocellular carcinoma (HCC) treated with sorafenib. This study assessed the value of alternative radiological criteria to evaluate response in HCC patients treated with sorafenib. PATIENTS AND METHODS: A retrospective blinded central analysis was performed of computed tomography (CT) scans from baseline and the first tumor evaluation in consecutive patients treated with sorafenib over a 2-year period in a single institution. Four different evaluation criteria were used: Choi, European Association for the Study of the Liver (EASL), modified RECIST (mRECIST), and RECIST 1.1. RESULTS: Among 82 HCC patients, 64 with Barcelona Clinic Liver Cancer stage B-C were evaluable with a median follow-up of 22 months. Median duration of sorafenib treatment was 5.7 months, and median overall survival was 12.8 months. At the time of the first CT scan, performed after a median of 2.1 months, Choi, EASL, mRECIST, and RECIST 1.1 identified 51%, 28%, 28%, and 3% objective responses, respectively. Responders by all criteria showed consistent overall survival >20 months. Among patients with stable disease according to RECIST 1.1, those identified as responders by Choi had significantly better overall survival than Choi nonresponders (22.4 vs. 10.6 months; hazard ratio: 0.43, 95% confidence interval: 0.15-0.86, p = .0097). CONCLUSION: Choi, EASL, and mRECIST criteria appear more appropriate than RECIST 1.1 to identify responders with long survival among advanced HCC patients benefiting from sorafenib.

Advanced Hepatocellular Carcinoma: early evaluation of response to targeted therapy and prognostic value of Perfusion CT and Dynamic Contrast Enhanced-Ultrasound. Preliminary results.

PURPOSE: To investigate whether there is any correlation between standard endpoints and tumor perfusion measurements with Perfusion CT and Dynamic Contrast-Enhanced Ultrasonography (DCE-US) in patients with advanced Hepatocellular Carcinoma (HCC) treated with targeted therapy. MATERIALS AND METHODS: Nineteen patients were evaluated during targeted therapy (sorafenib n=16, sunitinib n=3). Changes in tumor perfusion measurements between baseline and month 1 were assessed and compared using RECIST progression criteria at month 2. RESULTS: Median time to progression according to RECIST was 117 days and median time to death was 208 days. Perfusion CT values before treatment were significantly increased in HCC compared to the surrounding liver (n=17, P<.02). Eleven patients received complete examinations with both techniques at baseline and month 1. A non-significant decrease was found in all Perfusion CT values between RECIST nonprogressors (n=7) and progressors (n=4): mean Blood Volume: -27.9 vs. -11.1% and mean Blood Flow: -25.0 vs. -11.7% respectively. With DCE-US, opposite changes were found (mean Area Under the Curve AUC: -38.3 vs. 436.3%). RECIST progression at month 2 was significantly correlated with a threshold 40% decrease in AUC (P=.015). None of the patients with a decrease in AUC≥40% was a progressor at month 2. CONCLUSION: Despite perfusion changes with both Perfusion CT and DCE-US in patients receiving treatment, only DCE-US at month 1 (with a decrease in the AUC of more than 40%) predicted non-progression at month 2 and may be a potential surrogate marker of tumor response during targeted therapy.

Transarterial chemoembolisation: effect of selectivity on tolerance, tumour response and survival.

AIMS: To compare selective and non-selective TACE techniques in the treatment of HCC with a special emphasis on clinical and liver tolerance, tumour response and survival. METHODS: 184 patients with advanced HCC were retrospectively included. Three different TACE techniques were compared: non selective lipiodol-chemotherapy + non selective embolisation (TACE-technique group 1), non selective lipiodol-chemotherapy + selective embolisation (group 2), and selective lipiodol-chemotherapy + selective embolisation (group 3). RESULTS: In multivariate analysis TACE-technique group is an independently significant prognostic factor for poor clinical tolerance, poor liver tolerance and tumour response. The rate of patients with poor clinical tolerance was lower in group 3 (27.0%) than in groups 1 (64.1%, p < 10(-3)) or 2 (66.7%, p < 10(-3)). The rate of patients with poor liver tolerance was higher in group 2 (34.0%) than in groups 1 (17.6%, p = 0.050) or 3 (6.9%, p = 0.011). The rate of patients with tumour response was higher when embolisation was selective versus non-selective, i.e., group 2 + 3 (78.7%) versus group 1 (62.5%, p = 0.054). Overall survival was not significantly different between the three groups (p = 0.383). CONCLUSION: Both selective techniques resulted in better tumour response. As for improving tolerance, our study suggests that the main technical factor is the use of selective lipiodol-chemotherapy injection.

Portal vein embolization with N-butyl cyanoacrylate before partial hepatectomy in patients with hepatocellular carcinoma and underlying cirrhosis or advanced fibrosis.

PURPOSE: To describe the safety, complications, and liver regeneration associated with the left liver after embolization of the right portal vein (PV) in patients with hepatocellular carcinoma (HCC) developed in the setting of advanced liver fibrosis and cirrhosis. MATERIALS AND METHODS: Forty patients (31 men, nine women; mean age, 62 years) with HCC underwent PV embolization over a 4-year period. Embolization was performed from a left PV percutaneous access with use of n-butyl cyanoacrylate (NBCA) mixed with iodized oil. Computed tomography (CT) volumetry was performed before and 1 month after PV embolization to measure the left lobe volume as well as the functional liver ratio defined by the ratio between the left lobe and the total liver volume minus tumoral volume. PV pressure and liver enzyme levels were compared before and 1 month after the procedure and complications were registered. Factors potentially affecting regeneration (age, sex, diabetes, chemoembolization, functional liver ratio before PV embolization, and Knodell histologic score) were evaluated by one-way and stepwise regression analysis. RESULTS: PV embolization could be achieved successfully in all cases. Two patients had partial PV thrombosis on the 1-month follow-up CT and two patients developed transient ascites after PV embolization. The left lobe volume increase was 41% +/- 32% after PV embolization and the functional liver ratio increased from 28% +/- 10% to 36% +/- 10% (P < .0001). Hypertrophy of the left lobe was greater in patients with a low functional liver ratio before PV embolization and those with an F3 fibrosis score. Other factors had no influence on left lobe regeneration. CONCLUSION: PV embolization with use of NBCA is feasible in patients with advanced fibrosis and cirrhosis. Hypertrophy of the left lobe of the liver after PV embolization has a statistically significant correlation with lower functional liver ratio and lower degrees of fibrosis.