Tumor response and survival varies in patients treated with transarterial chemoembolization (TACE) for intermediate stage hepatocellular carcinoma (HCC) and may be associated with several factors.

To evaluate safety and efficacy of TACE in patients with intermediate stage HCC and to identify factors related to tumor response and survival.

Consecutive patients with HCC treated with TACE between September 2008 and September 2018 were retrospectively reviewed.

In 87 patients (71 men; mean age = 68 ± 9 years), 327 TACE treatments were performed (mean = 3/patient; range = 1-12). Mean and median overall survival were 32 and 19 months, respectively. Survival rates at 30 days, one, three, and five years were 99%, 71%, 19%, and 8%, respectively. Objective response (OR) was seen in 84% and disease control (DC) was seen in 92% of the patients. Patients in whom peritumoral portal lipiodol enhancement (PPLE) was seen during TACE had better OR (97 vs. 73%; P = 0.007) and DC (100 vs. 85%; P = 0.024), and a reduced risk of death (hazard ratio [HR] = 0.52; 95% confidence interval = 0.32-0.86) compared to those without PPLE. Severe adverse events were rare (15%) and occurred more often in patients with a larger tumor size.

TACE was effective and safe in patients with intermediate stage HCC. Patients with PPLE during TACE had better tumor response and longer survival than those without PPLE. Severe adverse events occurred more often in patients with larger tumors.

To evaluate the influence of sarcopenia on survival in patients with hepatocellular carcinoma (HCC) treated with ⁹⁰Y radioembolization.

This single-center retrospective cohort study analyzed 82 consecutive patients (65 men and 17 women, mean age 65 years, range 31-83 years) with HCC treated with ⁹⁰Y radioembolization between December 2013 and December 2017. Sarcopenia was assessed on pre-procedure MRI performed within 100 days prior to ⁹⁰Y radioembolization by segmenting the paraspinal musculature at the level of the superior mesenteric artery origin and subtracting fat-intensity pixels to yield fat-free muscle area (FFMA). Sarcopenia was defined as FFMA ≤31.97 cm² for men and ≤28.95 cm² for women. Survival at 90 days, 180 days, 1 year, and 3 years following initial treatment was assessed using medical and public obituary records.

Sarcopenia was identified in 30% (25/82) of patients. Death was reported for 49% (32/65) of males and 71% (8/17) of females (mean follow-up 19.6 months, range 21 days-58 months). Patients with sarcopenia were found to have increased mortality at 180 days (31.8% vs. 8.9%) and 1 year (68.2% vs. 21.2%). Sarcopenia was an independent predictor of mortality adjusted for BCLC stage and sub-analysis demonstrated that sarcopenia independently predicted increased mortality for patients with BCLC stage B disease.

Sarcopenia was associated with increased 180-day and 1-year mortality in HCC patients undergoing ⁹⁰Y radioembolization. Sarcopenia was an independent predictor of survival adjusted for BCLC stage with significant deviation in the survival curves of BCLC stage B patients with and without sarcopenia.

Hepatocellular carcinoma (HCC) is the primary tumour of the liver with the greatest incidence, particularly in the elderly. Additionally, improvements in the treatments for chronic liver diseases have increased the number of elderly patients who might be affected by HCC. Little evidence exists regarding HCC in old patients, and the elderly are still underrepresented and undertreated in clinical trials. In fact, this population represents a complex subgroup of patients who are hard to manage, especially due to the presence of multiple comorbidities. Therefore, the choice of treatment is mainly decided by the physician in the clinical practice, who often tend not to treat elderly patients in order to avoid the possibility of adverse events, which may alter their unstable equilibrium. In this context, the clarification of the optimal treatment strategy for elderly patients affected by HCC has become an urgent necessity. The aim of this review is to provide an overview of the available data regarding the treatment of HCC in elderly patients, starting from the definition of "elderly" and the geriatric assessment and scales. We explain the possible treatment choices according to the Barcelona Clinic Liver Cancer (BCLC) scale and their feasibility in the elderly population.

Intermediate-stage Hepatocellular Carcinoma (HCC) represents a wide range of disease burden. Patients with different levels of liver function, tumor size, and number of lesions may all have intermediate-stage disease according to the Barcelona Clinic Liver Cancer (BCLC) staging system. Several minimally invasive image-guided locoregional therapies are available for the treatment of intermediate-stage HCC, including conventional transarterial chemoembolization (cTACE), drug-eluting bead TACE (DEB-TACE), yttrium-90 radioembolization (Y-90 RE), thermal ablation, bland embolization, and combination therapy. Available clinical evidence points to cTACE as the current gold standard for the locoregional treatment of intermediate-stage HCC. DEB-TACE is at best non-inferior to cTACE in terms of survival benefit. Y-90 RE is a maturing therapy, and some institutions have adopted it as first-line therapy for intermediate-stage HCC. Thermal ablation combined with TACE may be used in select patients, while bland embolization has only limited evidence for its use. The combination of locoregional therapy with VEGF inhibitors or immune checkpoint inhibitors has also been explored. This article will examine in detail the clinical evidence supporting available locoregional treatment options for intermediate-stage HCC.

To evaluate the clinical utility of bland arterial embolization using microspheres in patients with hypervascular liver metastases refractory to standard treatments.

Primary endpoints of this prospective single-arm non-comparative study were objective response and disease control rates (ORR and DCR), based on the modified Response Evaluation Criteria in Solid Tumors at 4 weeks after embolization. Secondary endpoints were ORR according to primary tumor, overall survival, progression-free survival (PFS), and safety.

Twenty-five patients with a median age of 66 years (range, 40-95 years) were enrolled in this study. The median maximum diameter of liver metastasis was 3.7 cm (range, 2.0-15.2 cm). Primary lesions were colorectal cancer in 12 patients (48%, 12/25), other cancer in 7 (28%, 7/25), neuroendocrine tumor in 4 (16%, 4/25), and sarcoma in 2 (8%, 2/25). ORR and DCR were 52% (13/25) and 72% (18/25) in all patients, 42% (5/12) and 75% (9/12) in colorectal cancer patients, and 62% (8/13) and 69% (9/13) in other malignant tumor patients (p = 0.43, p > 0.99). Median survival time was 19 months in all patients, 19 months in colorectal cancer patients, and 8 months (p = 0.16) in other malignant tumor patients. Median PFS time was 4 months in all patients, 4 months in colorectal cancer patients, and 6 months (p = 0.0085) in other malignant tumor patients. There were no grade-3 or -4 adverse events.

Microsphere embolization appears to be an effective and safe treatment for hypervascular liver metastases refractory to standard treatments.

Several scoring systems have been proposed to predict the outcome of transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). However, the application of these scores to a bridging to transplant setting is poorly validated. Evaluation of the applicability of prognostic scores for patients undergoing TACE in palliative intention vs. bridging therapy to liver transplantation (LT) is necessary.

Between 2008 and 2017, 148 patients with HCC received 492 completed TACE procedures (158 for bridging to transplant; 334 TACE procedures in palliative treatment intention at our center and were analyzed retrospectively. Scores (ART, CLIP, ALBI, APRI, SNACOR, HAP, STATE score, Child-Pugh, MELD, Okuda and BCLC) were calculated and evaluated for prediction of overall survival. ROC analysis was performed to assess prediction of 3-year survival and treatment discontinuation.

In patients receiving TACE in palliative intention most scores predicted OS in univariate analysis but only mSNACOR score (p = 0.006), State score (p < 0.001) and Child-Pugh score (p < 0.001) revealed statistical significance in the multivariate analysis. In the bridging to LT cohort only the BCLC score revealed statistical significance (p = 0.002).

Clinical usability of suggested scoring systems for TACE might be limited depending on the individual patient cohorts and the indication. Especially in patients receiving TACE as bridging to LT none of the scores showed sufficiently applicability. In our study Child-Pugh score, STATE score and mSNACOR score showed the best performance assessing OS in patients with TACE as palliative therapy.

The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is progressively increasing. The aim of this study was to determine the safety and efficacy of conventional transarterial chemoembolization (TACE) in elderly HCC patients compared with younger adults.

A consecutive cohort of unresectable HCC patients treated with TACE as a first-line treatment was retrospectively analyzed. Patients were categorized into "elderly" (≥ 70 years, 80 patients) and "younger" (< 70 years, 145 patients). Liver-related death and progression-free survival after TACE were compared before and after propensity score matching. A competing risk regression analysis was used for univariate/multivariate survival data analysis.

cTACE was well tolerated in both groups. The cumulative risk of both liver-related death and progression-free survival after cTACE was comparable between "elderly" and "younger" (death: 73.8% vs 69.4%, P = 0.505; progression-free survival: 48.2% vs 44.8%, P = 0.0668). Propensity model matched 61 patients in each group for gender and Barcelona Clinic Liver Cancer staging. Even after matching, the cumulative risk of liver-related death and of progression-free survival did not differ between the two groups. At multivariate analysis, Child-Pugh class, tumor gross pathology and alpha-fetoprotein were independently associated with the liver-related mortality risk.

This study confirms that TACE is well tolerated and effective in patients aged 70 years or more with unresectable HCC as it is for their younger counterparts (< 70 years). Liver-related mortality was not associated with age ≥ 70 years and primarily predicted by tumor multifocality, Child-Pugh class B and an increased alpha-fetoprotein value (> 31 ng/ml).

Hepatocellular carcinoma (HCC), is the sixth most frequent form of cancer and leads to the fourth highest number of deaths each year. HCC results from a combination of environmental factors and aging as there are driver mutations at oncogenes which occur during aging. Most of HCCs are diagnosed at advanced stage preventing curative therapies. Treatment in advanced stage is a challenging and pressing problem, and novel and well-tolerated therapies are urgently needed. We will discuss further advances beyond sorafenib that target additional signaling pathways and immune checkpoint proteins. The scenario of possible systemic therapies for patients with advanced HCC has changed dramatically in recent years. Personalized genomics and various other omics approaches may identify actionable biochemical targets, which are activated in individual patients, which may enhance therapeutic outcomes. Further studies are needed to identify predictive biomarkers and aberrantly activated signaling pathways capable of guiding the clinician in choosing the most appropriate therapy for the individual patient.

The global population is aging, and so the number of older cirrhotic patients is increasing. Older patients are characterised by a risk of frailty and comorbidities, and age is a risk factor for mortality in cirrhotic patients. The incidence of non-alcoholic fatty liver disease as an aetiology of cirrhosis is increasing, while that of chronic viral hepatitis is decreasing. Also, cirrhosis is frequently idiopathic. The management of portal hypertension in older cirrhotic patients is similar to that in younger patients, despite the greater risk of treatment-related adverse events of the former. The prevalence of hepatocellular carcinoma increases with age, but its treatment is unaffected. Liver transplantation is generally recommended for patients < 70 years of age. Despite the increasing prevalence of cirrhosis in older people, little data are available and few recommendations have been proposed. This review suggests that comorbidities have a considerable impact on older cirrhotic patients.

Background During transarterial chemoembolization (TACE), cone-beam computed tomography (CBCT) can be used for tumor and feeding vessel detection as well as postembolization CT imaging. However, there will be additional radiation exposure from CBCT. Purpose To evaluate the additional dose raised through CBCT-assisted guidance in comparison to TACE procedures guided with pulsed digital subtraction angiography (DSA) alone. Material and Methods In 70 of 140 consecutive patients undergoing TACE for liver cancer, CBCT was used to facilitate the TACE. Cumulative dose area product (DAP), cumulative kerma(air), DAP values of DSA, total and cine specific fluoroscopy times (FT) of 1375 DSA runs, and DAP of 91 CBCTs were recorded and analyzed using Spearman's correlation, Mann-Whitney U-test, and Kruskal-Wallis test. P values < 0.05 were considered significant. Results Additional CBCT increased DAP by 2% ( P = 0.737), kerma(air) by 24.6% ( P = 0.206), and FT by 0.02% ( P = 0.453). Subgroup analysis revealed that postembolization CBCT for detection of ethiodized oil deposits added more DAP to the procedure. Performing CBCT-assisted TACE, DSA until first CBCT contributed about 38% to the total DAP. Guidance CBCT acquisitions conduced to 6% of the procedure's DAP. Additional DSA for guidance after CBCT acquisition required approximately 46% of the mean DAP. The last DSA run for documentation purposes contributed about 10% of the DAP. Conclusion CBCT adds radiation exposure in TACE. However, the capability of CBCT to detect vessels and overlay in real-time during fluoroscopy facilitates TACE with resultant reduction of DAPs up to 46%.

Interventional radiology plays a major role in the modern management of liver cancers, in primary hepatic malignancies or metastases and in palliative or curative situations. Radiological treatments are divided in two categories based on their approach: endovascular treatment and direct transcapsular access. Endovascular treatments include mainly three applications: transarterial chemoembolization (TACE), transarterial radioembolization (TARE) and portal vein embolization (PVE). TACE and TARE share an endovascular arterial approach, consisting of a selective catheterization of the hepatic artery or its branches. Subsequently, either a chemotherapy (TACE) or radioembolic (TARE) agent is injected in the target vessel to act on the tumor. PVE raises the volume of the future liver remnant in extended hepatectomy by embolizing a portal vein territory which results in hepatic regeneration. Direct transcapsular access treatments involve mainly three techniques: radiofrequency thermal ablation (RFA), microwave thermal ablation (MWA) and percutaneous ethanol injection (PEI). RFA and MWA procedures are almost identical, their clinical applications are similar. A probe is deployed directly into the tumor to generate heat and coagulation necrosis. PEI has known implications based on the chemical toxicity of intra-tumoral injection with highly concentrated alcohol by a thin needle.

To investigate accuracy of intraprocedural cone beam computed tomography (CBCT) compared to fluoroscopy for detection of lipiodol retention pattern during conventional transarterial chemoembolization (cTACE) of hepatocellular carcinoma (HCC) and its correlation with short-term response.

Between September 2013 and July 2014, 29 patients with HCC underwent chemoembolization of 51 tumors (mean diameter 28.1 mm, range 10.0-136.3 mm). Lipiodol retention pattern was assessed by CBCT at the endpoint of cTACE compared by fluoroscopy. Depending on the pattern of tumor covered by lipiodol three classes were defined: complete (more than 90 %, no peripheral defects), moderate (50-90 %, some with or without peripheral defects), and poor (less than 50 %). Tumor response was assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST) based on follow-up contrast enhanced (CE) computed tomography (CT) or magnetic resonance imaging (MRI) obtained 4-6 weeks post-cTACE. Correlations between lipiodol retention patterns on CBCT and fluoroscopy as well as tumor response were assessed using multivariate logistic regression.

Of 51 hepatic tumors, 40 (78.4 %) had complete response (CR); 8 (15.7 %) had partial response (PR); 1 (2.0 %) had stable disease (SD); and 2 (3.9 %) had progressive disease (PD). The degree of lipiodol retention scored excellent, moderate, and poor, in fluoroscopic images vs CBCT images were 23 (45.1 %) vs 39 (76.5 %), 19 (37.3 %) vs 11 (21.6 %), and 9 (17.6 %) vs 1 (2.0 %), respectively. Lipiodol retention assessment with CBCT (Az = 0.75) is more accurate than fluoroscopy (Az = 0.54) in predicting target tumor response. Other than lipiodol retention pattern assessed with CBCT (p = 0.01), tumor size (p = 0.04) is an independent predictors of CR.

CBCT is more accurate than fluoroscopy in classification of lipiodol retention pattern in HCC tumors at the time of cTACE. CBCT could be used as a reliable intra precedural monitoring modality of cTACE.

Hepatocellular carcinoma (HCC) is a major health problem worldwide. The average life expectancy during the 20th century has increased in many parts of the world, and therefore the opportunities to examine elderly HCC patients have significantly increased worldwide. Many elderly patients develop HCC with intermediate to advanced stages of disease at the initial diagnosis, and have more comorbidities and compromised liver regeneration compared with younger patients. These circumstances show that elderly patients with HCC are poorer candidates for surgical resection or transplantation. The aim of the present review was to focus on the clinical features and prognosis of elderly HCC patients not indicated for surgical resection including multimodal treatment. Although the chronological age of 60 or 65 years as the definition of an elderly person is accepted in most countries, many studies in our review article define elderly as those aged 75 years or older. Geriatr Gerontol Int 2017; 17: 189-201.

To evaluate changes in imaging findings on CT during hepatic arteriography (CTHA) and CT during arterial portography (CTAP) by balloon occlusion of the treated artery and their relationship with iodized oil accumulation in the tumor during balloon-occluded transcatheter arterial chemoembolization (B-TACE).

Both B-TACE and angiography-assisted CT were performed for 27 hepatocellular carcinomas. Tumor enhancement on selective CTHA with/without balloon occlusion and iodized oil accumulation after B-TACE were evaluated. Tumorous portal perfusion defect size on CTAP was compared with/without balloon occlusion. Factors influencing discrepancies between selective CTHA with/without balloon occlusion and the degree of iodized oil accumulation were investigated.

Among 27 tumors, tumor enhancement on selective CTHA changed after balloon occlusion in 14 (decreased, 11; increased, 3). In 18 tumors, there was a discrepancy between tumor enhancement on selective CTHA with balloon occlusion and the degree of accumulated iodized oil, which was higher than the tumor enhancement grade in all 18. The tumorous portal perfusion defect on CTAP significantly decreased after balloon occlusion in 18 of 20 tumors (mean decrease from 21.9 to 19.1 mm in diameter; p = 0.0001). No significant factors influenced discrepancies between selective CTHA with/without balloon occlusion. Central area tumor location, poor tumor enhancement on selective CTHA with balloon occlusion, and no decrease in the tumorous portal perfusion defect area on CTAP after balloon occlusion significantly influenced poor iodized oil accumulation in the tumor.

Tumor enhancement on selective CTHA frequently changed after balloon occlusion, which did not correspond to accumulated iodized oil in most cases.

Designing of theranostics and dual or multi-modality contrast agents are currently two of the hottest topics in biotechnology and biomaterials science. However, for single entity theranostics, a right ratio of their diagnostic component and their therapeutic component may not always be realized in a composite suitable for clinical application. For dual/multiple modality molecular imaging agents, after in vivo administration, there is an optimal time window for imaging, when an agent is imaged by one modality, the pharmacokinetics of this agent may not allow imaging by another modality. Due to reticuloendothelial system clearance, efficient in vivo delivery of nanoparticles to the lesion site is sometimes difficult. The toxicity of these entities also remains poorly understood. While the medical need of theranostics is admitted, the business model remains to be established. There is an urgent need for a global and internationally harmonized re-evaluation of the approval and marketing processes of theranostics. However, a reasonable expectation exists that, in the near future, the current obstacles will be removed, thus allowing the wide use of these very promising agents.

To evaluate balloon-occluded arterial stump pressure (BOASP), which is responsible for effective balloon-occluded transarterial chemoembolization (B-TACE), at each hepatic arterial level before B-TACE using a 1.8-French tip microballoon catheter for unresectable hepatocellular carcinoma (HCC).

The BOASP at various embolization portions was retrospectively investigated. "Selective" and "non-targeted" BOASP was defined as the BOASP at the subsegmental or segmental artery and the lobar artery, respectively.

The measurement of the BOASP was carried out in 87 arteries in 47 patients. BOASP > 64 mmHg was revealed in the caudate lobe artery (A1) and the left medial segmental (A4), right anterior superior segmental (A8), anterior segmental, right and left hepatic arteries. Significant difference was noted in the incidence of BOASP above 64 mmHg between "non-targeted" and "selective" BOASP (p = 0.01). "Non-targeted" BOASP was significantly greater than "selective" BOASP (p = 0.0147). In addition, the BOASP in A1, 4, 8 and the anterior segmental arteries were significantly greater than in the other subsegmental and segmental arteries (p = 0.0007).

"Non-targeted" B-TACE should be avoided to perform effective B-TACE and "selective" B-TACE at A1, 4, 8 and the anterior segmental arteries may become less effective than at the other segmental or subsegmental arteries.

This retrospective study was carried out to compare the outcomes between elderly (≥70 years of age) and nonelderly patients (<70 years of age) with advanced hepatocellular carcinoma (HCC) who received sorafenib combined with transarterial chemoembolization (TACE).

88 patients with a confirmed diagnosis of advanced HCC were enrolled in this study. Of these, 24 elderly patients were matched with 48 nonelderly patients at a 1:2 ratio using propensity score matching to minimize selection bias. The related adverse events and survival benefits were compared between the two groups.

Sorafenib combined with TACE was equally well tolerated in both age groups, and grade 3 or 4 adverse events were similarly observed in 54.2% of elderly and 50.0% of nonelderly patients (P = 0.739). There were no significant differences in survival time between the elderly and nonelderly patients (P = 0.876). Significant prognostic factors for overall survival as identified by multivariate analysis were the Child-Pugh score and portal vein invasion.

Sorafenib combined with TACE may be well tolerated and effective in elderly patients with advanced HCC. Age alone is not a parameter for the treatment of advanced HCC patients.

Although transcatheter arterial chemoembolization (TACE) has been widely used as a palliative treatment for unresectable hepatocellular carcinoma (HCC), its actual efficacy and prognostic usefulness have not been clarified in past studies.

The aim of the study is to investigate the efficacy, complications, and prognostic factors of the TACE in unresectable HCC patients.

Thirty-two patients with unresectable HCC were treated with TACE. The procedure was performed with a combination of Lipiodol, doxorubicin, and cytomycin followed by gelatin-sponge particles embolization. CT-scan imaging and liver function tests (AST, ALT, ALP, BIL, and PT) were performed before and after the TACE. All patients were followed-up for 6-months.

Of all patients, 1 and 11 patients respectively, exhibited a complete response (CR) and a partial response (PR) (response rate, CR+PR, 44%). Data have shown that tumor size, number of lesions and number of involved segments are significantly reduced after the TACE performance (P < 0.05). No significant clinical adverse effect was observed in patients after the intervention. Also, liver function tests including AST, ALT, ALP, BIL, and PT did not significantly differ before and after the intervention (P > 0.05). The 6-month cumulative survival rates of the 32 patients were 78.1 %, respectively. Univariate analysis showed that survival correlated significantly with the following factors: tumor size; ≥ 8 cm versus < 8 cm (P < 0.010), serum ALP level; < 300 versus ≥ 300 (P < 0.043), and number of liver involved segments; < 2 versus ≥ 2 (P < 0.020).

We showed that in treatment of patients with unresectable hepatocellular carcinoma, TACE significantly improved the disease and the overall survival rate. Also, we introduce the tumor size, serum ALP level, and number of liver involved segments as prognostic factors of the procedure. Finally, TACE can be recommended as the initial treatment for unresectable HCC patients.

The number of elderly hepatocellular carcinoma (HCC) patients is expected to rise. We analyzed the impact of age on clinical presentations, treatment allocation, and long-term survival between elderly (≥75 years) and younger (<75 years) HCC patients. In this study, a total of 812 elderly and 2270 younger HCC patients were evaluated. The baseline information and long-term survival were compared in the entire population and in different treatment groups. A propensity score matching analysis with preset caliper width was utilized to compare survival differences in different patient subgroups. Elderly HCC patients had discrete characteristics compared with younger HCC patients. Elderly patients received surgical resection (SR) less frequently, while more elderly patients underwent radiofrequency ablation (RFA) and transarterial chemoembolization (TACE). Younger patients had significantly better long-term survival than the elderly patients in all patients and in patients receiving SR (both P<0.05). However, of the entire cohort, age was not an independent predictor of poor prognosis in the Cox multivariate model. The long-term survival was similar between 2 age groups in patients receiving RFA and TACE. In the propensity model, there were no significant survival differences among patients receiving SR, RFA, or TACE (all P>0.05). Among the elderly, the Cancer of the Liver Italian Program (CLIP) score provided the lowest Akaike information criterion value. In conclusion, advanced age is not associated with inferior treatment result in HCC patients receiving different therapeutic modalities. Elderly HCC patients should be encouraged for active treatment when indicated. The CLIP is an optimal prognostic model for outcome assessment.

To evaluate the technical feasibility and safety considerations of balloon-occluded transarterial chemoembolization (B-TACE) using a newly developed 1.8-French (Fr) tip microballoon catheter for hepatocellular carcinoma (HCC).

Between February 2013 and May 2013, 31 patients (20 males, 11 females; age range 56-85 years) underwent B-TACE using a 1.8-Fr tip microballoon catheter for unresectable HCC. The technical success rate, procedural complications, and adverse events of B-TACE were retrospectively investigated.

A total of 31 patients were subjected to 70 sessions of B-TACE using a 1.8-Fr tip microballoon catheter. The level of B-TACE was sub-subsegmental in 11, subsegmental in 35, segmental in 14, lobar in five, and right inferior phrenic artery in five sessions. The overall technical success rate was 99% (69 out of 70 sessions). As procedural complications, rupturing of the microballoon (n = 3) and aneurysmal dilatation at the site of balloon occlusion (n = 2) were encountered. There were no significant differences in any parameters between blood biochemical examination before and between two to four weeks after the procedure.

A 1.8-Fr tip microballoon catheter enables selective catheterization in patients with HCC and B-TACE using the 1.8-Fr tip microballoon catheter is a safe procedure.

Recent studies suggest that a combination of radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) may have theoretical advantages over TACE alone for treatment of hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the effectiveness and safety of radiofrequency ablation following first-line TACE treatment in the management of HCC beyond the Milan Criteria.

Forty-five patients who consecutively underwent RFA following first-line TACE treatment for HCC beyond the Milan criteria were enrolled in this study. RFA was performed within 1-2 months after TACE treatment in patients who had incomplete necrotic tumor nodules. Primary effectiveness, complications, survival rates, and prognostic factors were evaluated retrospectively.

Complete ablation was achieved in 76.2% of the lesions according to 1-month follow-up computed tomography/magnetic resonance imaging evaluation. The mean follow-up period was 30.9 months (range 3-94 months). There were no major complications after RFA therapy. The median overall survival was 29 months (range 20-38 months), with 1-, 2-, and 3-year survival of 89%, 61%, and 43%, respectively. Multivariate analysis revealed that tumor diameter (P = 0.045, hazard ratio [HR] = 0.228, 95% confidence interval [CI]: 0.054-0.968) and pretreatment serum alpha-fetoprotein level (P = 0.024, HR = 2.239, 95% CI: 1.114-4.500) were independent predictors for long-term survival.

HCC beyond the Milan criteria can be completely and safely ablated by radiofrequency ablation following first-line TACE treatment with a low rate of complications and favorable survival outcome. Further assessment of the survival benefits of combination treatment for HCCs beyond the Milan Criteria is warranted.

In this study, we analyzed the rates and patterns of recurrences in hepatocellular carcinoma (HCC) patients who had achieved complete remission (CR) by transarterial chemoembolization (TACE) or radiofrequency ablation (RFA), and also examined the differences of recurrence patterns between TACE-treated and RFA-treated groups.

We followed 309 consecutive HCC patients who achieved CR following TACE (n = 220) or RFA (n = 89) for a median of 68 months. Recurrence patterns were classified as local recurrence and secondary tumor according to location of recurrence (≤2 cm and >2 cm from primary tumor).

Recurred HCC had been found in 231 out of 309 patients (75%) with CR by TACE or RFA; 112 local recurrences (48%), 100 secondary tumor (43%) and 19 both (9%). The cumulative recurrence rates at 1, 3 and 5 years were 22%, 64% and 79%, respectively. The overall recurrences at 1, 3 and 5 years following CR in the TACE-treated group was not different from those in the RFA-treated group (21%, 68% and 81% vs 26%, 56% and 84%, respectively; P = NS) However, the cumulative occurrence rates of local recurrence rates at 1, 3 and 5 years were significantly higher in the TACE-treated group compared to the RFA-treated group (15%, 53% and 65% vs 15%, 27% and 34%, respectively; P = 0.001).

Recurrence of HCC is very common, even following CR by TACE or RFA. Especially, local recurrences are very frequent in cases who achieved CR by TACE, which suggests that additional ablation therapy may be beneficial to prevent recurrences following CR by TACE.

Assessment of patient performance status is often subjective. Sarcopenia--measurement of muscle wasting--may be a more objective means to assess performance status and therefore mortality risk following intra-arterial therapy (IAT).

Total psoas area (TPA) was measured on cross-sectional imaging in 216 patients undergoing IAT of hepatic malignancies between 2002 and 2012. Sarcopenia was defined as TPA in the lowest sex-specific quartile. Impact of sarcopenia was assessed relative to other clinicopathological factors.

Indications for IAT included hepatocellular carcinoma (51 %), intrahepatic cholangiocarcinoma (13 %), colorectal liver metastasis (7 %), or other metastatic disease (30 %). Median TPA among men (568 mm(2)/m(2)) was greater than women (413 mm(2)/m(2)). IAT involved conventional chemoembolization (54 %), drug-eluting beads (40 %), or yttrium-90 (6 %). Median tumor size was 5.8 cm; most patients had multiple lesions (74 %). Ninety-day mortality was 9.3 %; 3-year survival was 39 %. Factors associated with risk of death were tumor size (HR = 1.84) and Child's score (HR = 2.15) (all P < 0.05). On multivariate analysis, sarcopenia remained independently associated with increased risk of death (lowest vs. highest TPA quartile, HR = 1.84; P = 0.04). Sarcopenic patients had a 3-year survival of 28 vs. 44 % for non-sarcopenic patients.

Sarcopenia was an independent predictor of mortality following IAT with sarcopenic patients having a twofold increased risk of death. Sarcopenia is an objective measure of frailty that can help clinical decision-making regarding IAT for hepatic malignancies.

The European Network on Radioembolization with Yttrium-90 resin microspheres study group (ENRY) conducted a retrospective study to evaluate the outcomes among elderly (≥ 70 years) and younger patients (<70 years) with unresectable hepatocellular carcinoma (HCC) who received radioembolization at 8 European centers.

Patients with confirmed diagnosis of unresectable HCC who either progressed following resection or locoregional treatment and/or who were considered poor candidates for chemoembolization were evaluated by a multidisciplinary team for radioembolization with (90)Y-resin microspheres (SIR-Spheres; Sirtex Medical). The survival outcome and all adverse events were compared between the two age groups.

Between 2003 and 2009, 128 elderly and 197 younger patients received radioembolization. Patients in both groups had similar demographic characteristics. Many elderly and younger patients alike had multinodular, BCLC stage C disease, invading both lobes (p = 0.648). Elderly patients had a lower tumor burden, a smaller median target liver volume (p = 0.016) and appeared more likely to receive segmental treatment (p = 0.054). Radioembolization was equally well tolerated in both cohorts and common procedure-related adverse events were predominantly grade 1-2 and of short duration. No significant differences in survival between the groups were found (p = 0.942) with similar median survival in patients with early, intermediate or advanced BCLC stage disease.

Radioembolization appears to be as well-tolerated and effective for the elderly as it is for younger patients with unresectable HCC. Age alone should not be a discriminating factor for the management of HCC patients.

Chronic hepatitis C (HCV) is a significant risk factor for cirrhosis and subsequently hepatocellular carcinoma (HCC). HCV patients with cirrhosis are screened for HCC every 6 months. Surveillance for progression to cirrhosis and consequently access to HCC screening is not standardized. Liver biopsy, the usual test to determine cirrhosis, carries a significant risk of morbidity and associated mortality. Transient ultrasound elastography (fibroscan) is a non-invasive test for cirrhosis.

This study assesses the cost effectiveness of annual surveillance for cirrhosis in patients with chronic HCV and the effect of replacing biopsy with fibroscan to diagnose cirrhosis.

A Markov decision analytic model simulated a hypothetical cohort of 10,000 patients with chronic HCV initially without fibrosis over their lifetime. The cirrhosis surveillance strategies assessed were: no surveillance; current practice; fibroscan in current practice with biopsy to confirm cirrhosis; fibroscan completely replacing biopsy in current practice (definitive); annual biopsy; annual fibroscan with biopsy to confirm cirrhosis; annual definitive fibroscan.

Our results demonstrate that annual definitive fibroscan is the optimal strategy to diagnose cirrhosis. In our study, it diagnosed 20 % more cirrhosis cases than the current strategy, with 549 extra patients per 10,000 accessing screening over a lifetime and, consequently, 76 additional HCC cases diagnosed. The lifetime cost is £98.78 extra per patient compared to the current strategy for 1.72 additional unadjusted life years. Annual fibroscan surveillance of 132 patients results in the diagnosis one additional HCC case over a lifetime. The incremental cost-effectiveness ratio for an annual definitive fibroscan is £6,557.06/quality-adjusted life years gained.

Annual definitive fibroscan may be a cost-effective surveillance strategy to identify cirrhosis in patients with chronic HCV, thereby allowing access of these patients to HCC screening.

Hepatocellular carcinoma (HCC) remains a major public health problem. Transarterial chemoembolization (TACE) is recognized as the standard of care for patients with unresectable, asymptomatic, noninvasive and multinodular HCC. This procedure is based on percutaneous administration of a cytotoxic drug emulsified with Lipiodol followed by embolization of the tumour-feeding arteries. The standard procedure involves Lipiodol, an oily contrast medium which consists of a mixture of long-chain di-iodinated ethyl esters of poppy seed fatty acids. The aim of this review is to discuss the physical properties, tumour uptake behaviour and drug delivery effects of Lipiodol, the parameters influencing tumour uptake and future prospects. Lipiodol has a unique place in TACE as it combines three specific characteristics: drug delivery, transient and plastic embolization and radiopacity properties. Substantial heterogeneity in the physicochemical characteristics of Lipiodol/cytotoxic agent emulsions might reduce the efficacy of this procedure and justifies the current interest in Lipiodol for drug delivery.

To identify prognostic factors for survival in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization with doxorubicin-eluting beads (DEBs).

In a retrospective, single-center analysis, tumor- and patient-related factors were recorded for univariate and multivariate analyses via Kaplan-Meier and Cox regression. Infiltrative HCC phenotype and portal vein invasion (PVI) were correlated, and patients with either or both were classified as having radiographically advanced (RAdv) HCC. The primary endpoint was overall survival, which was calculated from the time of first DEB chemoembolization procedure.

A total of 168 patients underwent 248 procedures, of which 215 (86.7%) were outpatient procedures. Mean length of stay was 0.33 days, and 25 patients (10.1%) were readmitted within 30 days. A total of 33 patients underwent liver transplantation and were excluded from survival analyses. A total of 130 had cirrhosis; 62, 50, and 18 had Child class A, B, and C disease, respectively. Forty-one patients had infiltrative HCC phenotype, 28 of whom also had PVI. Multivariate analysis of survival in all patients showed α-fetoprotein (AFP), performance status (PS), RAdv HCC, Child classification, albumin level, and ascites to predict survival. In patients without RAdv HCC, AFP, PS, Child classification, albumin level, and International Normalized Ratio were independent predictors. Increased bilirubin level was not an independent risk factor for death.

Independent prognostic factors in patients with HCC undergoing DEB chemoembolization have been identified. Increased bilirubin level was not an independent risk factor. These data can be used in HCC patient selection and counseling for DEB chemoembolization.

Transcatheter arterial chemoembolization (TACE) is an effective treatment for hepatocellular carcinoma (HCC) that can occasionally lead to the shortening of life expectancy. We aimed to make a new and more accurate prognostic model taking into account the course of disease after TACE.

We performed a prospective cohort study involving 100 HCC patients who underwent TACE at Kobe University Hospital. Indirect calorimetry and blood biochemical examinations were performed before and 7 days after TACE. Time-dependent and time-fixed factors associated with 1-year mortality after TACE were assessed by multivariate analyses. A predictive model of 1-year mortality was established by the combination of odds ratios of these factors. Multivariate analyses showed that the ratio of non-protein respiratory quotient (npRQ) (7 days after/before TACE) and Cancer of Liver Italian Program (CLIP) score were independent factors of 1-year mortality after TACE (p = 0.014 and 0.013, respectively). Patient-specific 1-year mortality risk scores can be calculated by summarizing the individual risk scores and looking up the patient-specific risk on the graph.

The short-term reduction of npRQ was a time-dependent prognostic factor associated with overall survival in HCC patients undergoing TACE. CLIP score was a time-fixed prognostic factor associated with overall survival. Using the prediction model, which consists of the combination of time-dependent (npRQ ratio) and time-fixed (CLIP score) prognostic factors, 1-year mortality risk after TACE would be better estimated by taking into account changes during the course of disease.

Sorafenib is the only systemic treatment shown to be effective against advanced hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC) has been selected as an alternative therapeutic option for advanced HCC. We investigated the efficacy and safety of HAIC as an alternative treatment for sorafenib in advanced HCC.

Between May 2008 and March 2011, 20 consecutive patients were treated with sorafenib monotherapy as a first-line treatment and 21 consecutive patients who could not take sorafenib because of cost were treated with HAIC monotherapy as an alternative. Sorafenib was administered in 400 mg b.i.d. doses. For HAIC, daily cisplatin (7 mg/m(2) on days 1-5) and 5-FU (170 mg/m(2) on days 1-5) were infused every 4 weeks. We assessed overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and toxicity.

Median OS was 4.9 months (95% CI, 3.4-6.4) for sorafenib and 7.3 months (95% CI, 4.5-10.2) for HAIC (P = 0.599). Median PFS was 2.0 months (95% CI, 1.96-2.05) versus 3.0 months (95% CI, 1.98-4.02) for sorafenib and HAIC, respectively (P = 0.303). ORR and disease control rate (DCR) for sorafenib were 10.0 and 35.0% versus 19.0 and 38.1% for HAIC (ORR, P = 0.413; DCR, P = 0.837). Patients treated with HAIC more frequently exhibited grade 3/4 neutropenia (23.8 vs 0% for sorafenib), whereas sorafenib therapy showed grade 3/4 hand-foot skin reaction in 10% of patients.

HAIC is a useful alternative treatment for advanced HCC and further prospective investigations are required.

Transcatheter arterial chemoembolization (TACE) is an effective treatment for hepatocellular carcinoma (HCC), but it sometimes makes liver function worse. The pre-TACE prediction of liver dysfunction after TACE would be helpful to avoid long-term liver dysfunction.

We performed a case-control study in 100 HCC patients who underwent TACE at Kobe University Hospital. Urinary/blood biochemical examinations were performed before TACE. As an indicator of liver function, Child's score was also evaluated before and 3 months after TACE. Cases with and without an increase of 2 points or more in the Child's score were compared, and independent risk factors were statistically examined. A pre-TACE predictive model of an increase of 2 points or more in the Child's score after TACE was developed using logistic regression.

Univariate analyses showed that des-γ-carboxy prothrombin (DCP) and lactate dehydrogenase (LDH) before TACE were significantly higher in the Child's score-deteriorated group than in the group with no deterioration (p = 0.036 and 0.003, respectively). All possible multivariate regressions showed that DCP (p = 0.003) and LDH (p = 0.002) were independent factors determining the deterioration of Child's class. A predictive model was developed, as follows: exp(0.014 × LDH + 0.572 × ln(DCP) - 8.655)/(1 + exp(0.014 × LDH + 0.572 × ln(DCP) - 8.655)). The model discriminated well, with AUC being 0.837 (95 % confidence interval [CI] 0.662-1.000). The optimal cut-off point was 0.073, and the sensitivity and specificity were 90.9 and 69.7 %, respectively.

High values of DCP and LDH before TACE were associated with the long-term deterioration of liver function. Our pre-therapeutic prediction model could be useful to identify high-risk cases.

Transcatheter arterial chemoembolization (TACE) is an effective treatment for hepatocellular carcinoma (HCC) that can cause deterioration of liver function. We aimed to make an early predictive model of long-term liver dysfunction after TACE.

We performed a prospective cohort study involving 109 HCC patients who underwent TACE at Kobe University Hospital. Indirect calorimetry and blood biochemical examinations were performed before and 7 days after TACE. As an indicator of liver function, the Child's score was evaluated before and 3 months after TACE. Patients with and without Child's score deterioration were compared, and the independent risk factors for Child's score deterioration were statistically examined. An early predictive model of Child's score deterioration after TACE was developed using multivariate logistic regression.

Multivariate analyses showed that the non-protein respiratory quotient (npRQ) and prealbumin (preAlb) ratios (7 days after/before TACE) were independent determinants of Child's score deterioration (p = 0.039 and 0.020, respectively). Decreases of the npRQ and preAlb ratios were significantly related to increases of Child's score 3 months after TACE (p = 0.007 and 0.002, respectively). The following predictive model of Child's score deterioration was developed: exp(-6.383 × npRQ ratio - 3.038 × preAlb ratio + 7.755)/(1 + exp(-6.383 × npRQ ratio - 3.038 × preAlb ratio + 7.755)). The model discriminated well between patients with and without Child's score deterioration (area under the receiver operating curve [ROC]; AUC 0.713; 95% confidence interval [CI] 0.613-0.812). The optimal cut-off point for the Child's score was 0.449, and the sensitivity and specificity of the model were 57.1 and 79.1%, respectively.

Reductions in npRQ and preAlb 7 days after TACE were associated with the long-term deterioration of liver function. With our model, we were able to identify high-risk patients.

The decreased portal blood flow and the potential decrease in arterial nutrient hepatic blood flow after creation of a transjugular intrahepatic portosystemic shunt (TIPS) makes the treatment of hepatocellular carcinoma (HCC) challenging.

To evaluate the safety and efficacy of transarterial chemoembolization (TACE) after TIPS in patients with HCC.

From 1998 to 2009, 20 patients underwent selective (segmental or subsegmental) TACE for HCC after TIPS. Among 20 patients, seven patients had undergone one to three sessions of TACE for HCC before TIPS creation. TACE was performed using a mixture of iodized oil and cisplatin, and absorbable gelatin sponge particles. Tumor response, complications, and patient survival were evaluated after TACE.

After TACE, 14 of the 20 (70%) patients showed a tumor response, with only one (5%) experiencing a TACE-related major complication, spontaneous bacterial peritonitis. None of the patients who underwent TACE after TIPS died within 30 days. During the follow-up period (range 2.2-107 months; mean 32.6 months), 18 patients died and two remained alive. The median survival period after TACE was 23 months. Multivariate Cox regression analysis showed that tumor stage was the only independent prognostic factor for patient survival (P = 0.049).

Selective TACE may be safe and effective for the palliative treatment of HCC in patients with TIPS. Late tumor stage ( ≥III) was poor prognostic factor for determining the patient survival period after post-TIPS TACE.

  Sonazoid is a new contrast agent for ultrasonography (US). Contrast-enhanced ultrasonography (CEUS) using Sonazoid enables Kupffer imaging, which improves the sensitivity of hepatocellular carcinoma (HCC) detection. However, there are no studies on the cost-effectiveness of HCC surveillance using Sonazoid.

  We constructed a Markov model simulating the natural history of HCV-related liver cirrhosis (LC) patients, and compared three strategies (no surveillance, US surveillance and CEUS surveillance). The transition probability and cost data were obtained from published data. The simulation and analysis were performed using TreeAge pro 2009 software.

  When compared to the no surveillance group, the US and CEUS surveillance groups increased the life expectancy by 1.67 and 1.99 quality-adjusted life-years (QALY), respectively, and the incremental cost effectiveness ratio (ICER) were 17 296 $US/QALY and 18 384 $US/QALY, respectively. These results were both less than the commonly-accepted threshold of $US 50 000/QALY. Even if the CEUS surveillance group was compared with the US surveillance group, the ICER was $US 24 250 and thus cost-effective. Sensitivity analysis showed that the annual incidence of HCC and CEUS sensitivity were two critical parameters. However, when the annual incidence of HCC is more than 2% and/or the CEUS sensitivity is more than 80%, the ICER was also cost-effective.

  Contrast-enhanced ultrasonography surveillance for HCC is a cost-effective strategy for LC patients and gains their longest additional life years, with similar degree of ICER in the US surveillance group. CEUS surveillance using Sonazoid is expected to be used not only in Japan, but also world-wide.

To investigate the accuracy of ethiodized oil as an imaging marker of chemotherapy drug delivery after liver tumor chemoembolization in an animal model of hepatocellular carcinoma.

Eleven VX2 liver tumors (mean diameter, 1.9 cm ± 0.4) in six New Zealand White rabbits were treated with chemoembolization using ethiodized oil and doxorubicin emulsion, followed by immediate euthanasia. Postprocedure noncontrast computed tomography (CT) was used to evaluate intratumoral ethiodized oil distribution and calculate iodine content within four peripheral tumor quadrants and the tumor core at a central tumor slice (N = 55 total tumor sections). Liquid chromatography/tandem mass spectrometry (LC-MS/MS) was then used to directly measure doxorubicin concentration in the same tissue sections. Statistical correlation was performed between tissue iodine content and doxorubicin concentration by using linear regression.

Chemoembolization was successfully performed in all tumors via the left or proper hepatic artery. A mean of 0.9 mL ± 0.6 ethiodized oil and 1.8 mg ± 1.2 doxorubicin were injected. CT-calculated tissue iodine content averaged 335 mg/mL ± 218. Corresponding LC-MS/MS analysis yielded a mean doxorubicin concentration of 15.8 μg/mL ± 14.3 in each sample. Although iodine content (391 mg/mL vs 112 mg/mL; P = .000) and doxorubicin concentration (18.0 μg/mL vs 7.2 μg/mL; P = .023) were significantly greater along peripheral tumor sections compared with the tumor core, no significant predictable correlation was evident between these measures (R(2) = 0.0099).

Tissue ethiodized oil content is a poor quantitative predictor of local doxorubicin concentration after liver tumor chemoembolization. Future studies should aim to identify a better imaging marker for chemoembolization drug delivery.

Rupture of hepatocellular carcinoma (HCC) is a life-threatening condition accompanied by hemorrhage. Transarterial embolization/chemoembolization (TAE/TACE) can be used as the first-line treatment to achieve initial homeostasis.

To investigate the outcome of TAE/TACE for spontaneous ruptured HCC and to determine the prognostic factors affecting survival.

We retrospectively reviewed the clinicoradiologic data of 47 patients (8 women, 39 men; median age 64.4 years) with serum bilirubin levels <3.0 mg/dL that underwent TAE/TACE for ruptured HCC between January 2004 and June 2010. Survival rates were estimated using the Kaplan-Meier method and prognostic factors of poor survival were obtained by univariate and multivariate analyses.

The clinical success rate of TAE/TACE was 94% (44/47). The median survival time was 179.6 days. The 1-month, 3-month, 6-month, and 12-month survival rates were 75%, 54%, 48%, and 43%, respectively. Old age, a previous history of TACE for HCC, low initial hemoglobin level, higher blood transfusion requirement, Child-Pugh class C, high serum bilirubin level, low serum albumin level, prolonged prothrombin time, high serum creatinine level on admission, presence of encephalopathy, severe ascites, lobar TAE/TACE, presence of portal vein thrombosis, and tumors involving both lobes were associated with poor survival. Multivariate analysis revealed that higher blood transfusion requirement, Child-Pugh class C, presence of portal vein thrombosis, and tumors involving both lobes were significant predictors of poor survival.

TAE/TACE is effective for achieving initial hemostasis, which is critical to survival. Regardless of successful TAE/TACE, the survival rate in patients with Child-Pugh class C remains poor. Portal vein thrombosis and tumor extent are significant image parameters for predicting survival after TAE/TACE for ruptured HCC.