Clinical trial of cisplatin-conjugated gelatin microspheres for patients with hepatocellular carcinoma

Purpose

We report our initial experience with the transarterial chemoembolization (TACE) of unresectable hepatocellular carcinoma (HCC) using cisplatin-conjugated gelatin microspheres (Cis-GMS).

Methods and material

Nineteen patients with 25 HCC nodules (mean diameter 23.0?mm) were treated by selective TACE using 50- to 100-??m Cis-GMS. Tumor necrosis and postembolization syndrome were assessed during the follow-up. The tumor response was evaluated on contrast-enhanced computed tomography images at 1 and 3?months after TACE using Cis-GMS.

Results

All procedures were technically successful in all patients; following the TACE using Cis-GMS, there were no major complications, and postembolization syndrome was minimal. At the 1-month follow-up, the response rate was 12 of the 25 (48%) and 21 of the 25 (84%) HCC nodules based on RECIST 1.1 and EASL criteria, respectively; at the 3-month follow-up, it was 10 of the 25 (40%) and 14 of the 25 (56%) HCC nodules, respectively.

Conclusion

Our initial experience with using Cis-GMS for TACE suggests that these drugs may represent an optimal treatment option for the treatment of advanced HCC and that the use of gelatin microspheres loaded with chemotherapeutic agents warrants further study.     

Sequential transarterial chemoembolization for unresectable advanced hepatocellular carcinoma

Purpose The aim of this prospective study was to evaluate the feasibility, safety, and efficacy of sequential transarterial chemoembolization (TACE) for patients with unresectable advanced hepatocellular carcinoma (HCC). Methods Twenty-one consecutive patients with unresectable T3 and T4 HCC were treated by sequential TACE (median time interval between treatments 7 weeks) up to six times with an emulsion of lipiodol, epirubicin, and cisplatin. All TACE procedures were performed as unilobar or whole-liver chemoembolization. Results An average of 3.9 TACE procedures were performed per patient. One primary and two secondary technical failures occurred. No procedural death was observed. After exclusion of the patient with the primary technical failure and 3 patients with extrahepatic disease, the survival rates for the remaining 17 patients at 6, 12, 18, and 24 months were 70.6%, 52.9%, 44.1%, and 33.1%, respectively. Conclusion Sequential TACE is a safe procedure in patients with unresectable advanced HCC and feasible in most cases. It seems to prolong the survival time compared with historical series of untreated patients.     

Prospective comparison of transcatheter arterial chemoembolization with Lipiodol-epirubicin and Lipiodol-cisplatin for treatment of recurrent hepatocellular carcinoma

Purpose

The aim of this study was to compare the safety and short-term efficacy of transcatheter arterial chemoembolization (TACE) using cisplatin-Lipiodol suspension (CP/Lp) with that using epirubicin-Lipiodol emulsion (EP/Lp) in patients with recurrent hepatocellular carcinoma (HCC).

Materials and methods

A total of 28 HCC patients were enrolled prospectively and assigned to the CP/Lp group or EP/Lp group. Adverse effects related to TACE were graded; and the treatment effect (TE) on HCC nodules at 3 months and overall tumor response at 6 months were assessed as the endpoint.

Results

No significant difference was observed between the groups regarding the frequency of adverse effects of grade 3 or less. The TE rates for 100% necrosis plus >50% necrosis in 62 HCC nodules in the CP/Lp group and 75 HCC nodules in the EP/Lp group were 72.6% and 66.7%, respectively (P = 0.894). Overall tumor response revealed that six patients (50.0%) in the CP/Lp group and six patients (37.5%) in the EP/Lp group had a partial response plus a complete response, with no significant difference (P = 0.615). TACE-free control curves for both groups revealed no significant difference (P = 0.513).

Conclusion

No significant difference was found with regard to adverse effects, the treatment effect on HCC nodules, or overall tumor response between the CP/Lp and EP/Lp groups.     

Lipiodol Trans-arterial Chemoembolization of Hepatocellular Carcinoma with Idarubicin: First Experience

Background

There is still no consensus about the best chemotherapeutic agent for transarterial chemoembolization (TACE). A recent in vitro study demonstrated that idarubicin, an anthracycline, was by far the most cytotoxic drug on human hepatocellular carcinoma (HCC) cell lines. Idarubicin is much more lipophilic than doxorubicin, leading to higher cell penetration through lipidic membranes and greater accumulation of the drug in the lipiodol. Furthermore, idarubicin has the ability to overcome multidrug resistance. Therefore, we designed this pilot human study to evaluate the safety and efficacy of lipiodol TACE using idarubicin.

Methods

In 21 consecutive patients treated by lipiodol TACE with idarubicin (10 mg) for HCC, safety data, tumor response (Response Evaluation Criteria in Solid Tumors, mRECIST), time to treatment failure (TTTF), and overall survival were evaluated.

Results

Postembolization syndrome was observed after 30.9 % (17 of 55) of sessions. No patient died from a TACE-related complication. No hematological grade 3–5 adverse event was observed. At least one grade 3 or higher adverse event occurred in 19 % (4 of 21) of patients. On imaging, no progression was encountered; four patients (24 %) exhibited stable disease, 12 (57 %) exhibited a partial response, and five (19 %) exhibited a complete response. Median TTTF was 16.7 months (Kaplan–Meier analysis). At 6 months, 94.7 % (95 % confidence interval [CI] 68.1–99.2) of patients did not reach treatment failure, whereas treatment failure was not reached in 50.6 % (95 % CI 21.6–73.9) of patients at 1 year. Overall survival was 83.5 % (95 % CI 57–94.4) at 1 year.

Conclusion

Idarubicin seems safe and effective in lipiodol TACE of HCC. This warrants further study to determine the potential of this drug to replace doxorubicin for TACE.     

Warming Effect on Miriplatin–Lipiodol Suspension as a Chemotherapeutic Agent for Transarterial Chemoembolization for Hepatocellular Carcinoma: Preliminary Clinical Experience

Purpose

To retrospectively elucidate the preliminary clinical impact of warmed miriplatin–lipiodol suspension (MPT-LPD) when used as a chemotherapeutic agent for transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).

Materials and Methods

Between June and December 2010, TACE was performed with MPT-LPD at room temperature (RT group), and after January 2011, TACE with MPT-LPD warmed to 40 °C was performed (W group). The intraarterial appearance of MPT-LPD immediately after injection through microcatheters at the second-order branches was compared between the two groups with a 5-point grading system. Local therapeutic effects of HCCs as assessed by follow-up computed tomography (CT) obtained 1–3 months after TACE were compared between the groups with a 4-point grading system (TE1–TE4). After April 2011, angiography-assisted CT was routinely performed at TACE, and HCCs that revealed apparent corona enhancement (CE) were retrospectively selected. The degree of concordance between CE and MPT-LPD accumulation as assessed by CT immediately after TACE was assessed with a 3-point grading scale.

Results

MPT-LPD therapy resulted in a smooth and continuous appearance in the W group (grades 1, 2, 3, 4, and 5 were, respectively, 1, 2, 11, 18, and 4) compared to the RT group (4, 0, 1, 2, and 0). The W group (TE1, TE2, TE3, and TE4 were 1, 9, 11, and 12) revealed better local therapeutic effects than the RT group (6, 3, 9, and 0) (p < 0.05). CE was found in 26 HCC nodules, and concordance between CE and MPT-LPD accumulation was observed in 66 % (grades 1, 2, and 3 were, respectively, 2, 8, and 19).

Conclusion

Warmed MPT-LPD flowed more smoothly within vascular lumen, passed through tumor sinusoid of HCC, and had better local therapeutic effects at short-term observation than MPT-LPD at room temperature.     

Combined treatment,TACE and RF ablation,in HCC: preliminary results

PURPOSE: The aim of this study was to assess the effectiveness of a combination of percutaneous radiofrequency thermal ablation (RF), stop-flow and transcatheter arterial chemo-embolisation (TACE) in the treatment of hepatic neoplasms. MATERIALS AND METHODS: From December 1997 to September 2000, 34 patients with hepatocellular carcinoma (HCC) underwent radiofrequency thermoablation treatment. The choice of method was based on the type of lesion (HCC vs metastasis) and the following dimensional criteria: 1. RF without stop-flow associated with the injection of diagnostic Lipiodol in the case of a single nodule with a maximum diameter smaller than 3 cm; 2. RF with stop-flow of the hepatic artery associated with TACE in the case of a single nodule with a diameter greater than 3 cm; 3. RF with stop-flow of the hepatic artery associated with TACE in the case of 2-3 nodules, a subdivision was made into 2 groups according to the volume: smaller or greater than 80 ml. RESULTS: 10 out of 34 patients affected by HCC with a diameter smaller than 3cm, treated only with RF, demonstrated 100% necrosis in the follow-up period, which varied between 6 and 24 months (average 10 months). The remaining 24 patients affected by HCC and treated with RF associated with stop-flow and TACE showed responses related to the volume of the tumour: 1. patients with a single nodule with a diameter of 3-5 cm showed 100% necrosis; 2. patients affected by multifocal HCC with a maximum of 3 nodules and/or total tumour mass smaller than 80 ml, for a total of 9 lesions, showed 95% necrosis; 3. patients affected by multifocal HCC with more than 3 nodules (total mass less than 40% of liver volume) or tumour mass greater than 80ml, for a total of 13 lesions, showed 90% necrosis. In the group of patients affected by multiple nodules with volumes smaller than 80ml, the technique did not show complete effectiveness, thus these patients cannot be considered cured. Such aspects are even clearer in the more advanced stages. CONCLUSIONS: In our case study, radiofrequency proved effective with lesions up to 3cm in diameter. By reducing thermal dispersion, the association of the stop-flow technique with radiofrequency ablation, determines a greater volume of necrosis, which allows effective treatment of single nodules with a diameter of up to 5cm and/or multiple nodules. The association with TACE: 1. provided a way to highlight and treat lesions not recognizable through other imaging techniques; 2. increased the accumulation of lipid contrast in the tissue surrounding the lesion and in the vessels not occluded by thermal ablation in the lesions with diameters greater than 3 cm; 3. enabled further treatment of tumour residue possibly left untouched by thermal ablation in large tumours; 4. increased the amount of Lipiodol accumulated in normal tissue surrounding the lesion, made evident through the comparison of the dimensions of the nodule's blush between angiography and Lipiodol CT.     

Clinical utility and limitations of tumor-feeder detection software for liver cancer embolization

Purpose

To evaluate the clinical utility and limitations of a computer software program for detecting tumor feeders of hepatocellular carcinoma (HCC) during transarterial chemoembolization (TACE).

Materials and methods

Forty-six patients with 59 HCC nodules underwent nonselective digital subtraction angiography (DSA) and C-arm computed tomography (CT) in the same hepatic artery. C-arm CT data sets were analyzed using the software to identify potential tumor feeders during each TACE session. For DSA analysis, 3 radiologists were independently assigned to identify tumor feeders using the DSA images in a separate session. The sensitivity of the 2 techniques in detecting tumor feeders was compared, with TACE findings as the reference standard. Factors affecting the failure of the software to detect tumor feeders were assessed by univariate and multivariate analyses.

Results

We detected 65 tumor feeders supplying 59 HCC nodules during TACE sessions. The sensitivity of the software to detect tumor feeders was significantly higher than that of the manual assessment using DSA (87.7% vs. 71.8%, P < 0.001). Multivariate analysis showed that a tumor feeder diameter of <1.0 mm (hazard ratio [HR], 56.3; P = 0.003) and lipiodol accumulation adjacent to the tumor (HR, 11.4; P = 0.044) were the significant predictors for failure to detect tumor feeders.

Conclusion

The software analysis was superior to manual assessment with DSA in detecting tumor feeders during TACE for HCC. However, the capability of the software to detect tumor feeders was limited by vessel caliber and by prior lipiodol accumulation to the tumor.     

Small nodular hepatocellular carcinoma treated by laser thermal ablation in high risk locations: preliminary results

Objectives

To demonstrate the effectiveness and the safety of laser thermal ablation (LTA) in patients with unresectable hepatocellular carcinoma (HCC) deemed not accessible for other percutaneous procedures (radiofrequency ablation, sclerotherapy).

Methods

From September 2003 to August 2008, 140 patients with HCC nodules were treated. In 49 patients, the lesions were localized in “critical sites”. A total of 29 men and 20 women (age range 51–79 years; Child–Pugh score A = 75.51%, B = 24.49%) with 52 nodules (mean diameter 2.0?±?1.2 cm) were treated in 95 percutaneous LTA sessions. We compared major and minor complications observed in the two groups of patients. Effectiveness was defined as the percentage of HCCs completely ablated after percutaneous LTA. Follow-up was carried out with computed tomography (CT) at 1, 3, 6, 9, and 12 months.

Results

No major complications or deaths were registered. In a few patients (8.16%), minor complications were observed. No substantial differences were observed on comparing the percentage of minor and major complications in these patients with the remaining patients. A difference in terms of effectiveness was found.

Conclusion

LTA can be considered a safe treatment in “critical nodules”.     

Transcatheter Arterial Chemoembolization (TACE) or Embolization (TAE) for Symptomatic Bone Metastases as a Palliative Treatment

Purpose

This study was designed to evaluate the effect of transcatheter arterial chemoembolization (TACE)/embolization (TAE) for symptomatic bone metastases especially in palliation.

Methods

Between April 2006 and December 2009, 24 bone metastatic lesions of 18 patients (8 women and 10 men; mean age, 64?years) underwent palliative TACE or TAE. A total of 40 sessions were performed, with 1?C4 sessions per lesion. The primary lesions included hepatocellular carcinoma, colorectal cancer, renal cell cancer, ovarian cancer, thyroid cancer, uterine cervical cancer, and esophageal cancer. Symptomatic lesions involved thoracic spine, lumbar spine, pelvis, rib, and femur. The procedures were performed with a coaxial catheter technique to catheterize selectively target arteries. If not possible due to small branches, blood flow alteration by coil was achieved. Gelatin sponge was the initial embolic materials. As anti-cancer agents, epirubicin, fluorouracil, and mitomycin were mainly used in consideration for primary lesion and past treatment.

Results

Sufficient devascularization of targeted lesions was obtained in 18 of 24 (75%) lesions without any serious complication. Pain relief was obtained in 20 lesions (83%), with significantly decrease in the visual analogue scale score (P?r?=?0.49, P?Conclusions Palliative TACE/TAE for symptomatic bone metastases could be a suitable treatment method because it is minimally invasive, repeatable, effective, and rapid-acting.     

Rationale Schnittbildgebung des hepatozellulären Karzinoms

Clinical/methodical issue

Both computed tomography (CT) and magnetic resonance imaging (MRI) constitute the gold standard in radiological imaging of hepatocellular carcinoma (HCC). In cases of typical contrast behavior each modality as a single dynamic technique allows the diagnosis of HCC. There is still a challenge in detection of small HCCs <?2 cm, in differentiating HCC and high-grade dysplasia from other benign liver lesions as well as the evaluation of hypovascular liver lesions in the cirrhotic liver.

Performance

Nowadays, both modalities achieve high detection rates of 90–100?% for lesions >?2 cm. Regarding lesions between 1 and 2 cm there is a higher sensitivity for MRI ranging between 80 and 90?% compared to 60–75?% with CT. Besides the multimodal diagnostic criteria, MRI provides significant benefits with the use of hepatobiliary contrast. Especially in combination with diffusion- weighted imaging (DWI) increased sensitivity and diagnostic accuracy compared to CT has been described for lesions sized <?2 cm. Regarding the differentiation from other hepatic nodules in the cirrhotic liver there is strong evidence that the coexistence of arterial enhancement and hypointensity on hepatobiliary imaging is specific for HCC. Moreover, hypointensity on hepatobiliary imaging is associated with a high positive predictive value (PPV) of up to 100?% for the presence of high-grade dysplasia and HCC.

Achievements

The use of MRI including hepatobiliary imaging and DWI has to be regarded as the best non-invasive imaging modality for the detection of HCC and for the characterization of nodules in patients with liver cirrhosis. In comparison to CT there are benefits regarding detection of small lesions <?2 cm and evaluation of hypovascular liver lesions in the context of the hepatocarcinogenesis including prognostic values of premalignant lesions.

Practical recommendations

Both MRI and CT provide a high diagnostic performance in evaluation of HCC in liver cirrhosis. With MRI there are considerable advantages regarding the detection rate and specificity. For daily clinical routine, CT offers a fast, reliable and easy available modality with benefits for patients in reduced general state of health and restricted compliance.     

MR characterisation of dysplastic nodules and hepatocarcinoma in the cirrhotic liver with hepatospecific superparamagnetic contrast agents: pathological correlation in explanted livers

Purpose

The authors sought to evaluate the potential of magnetic resonance (MR) imaging with superparamagnetic iron oxide (SPIO) contrast material for identifying, characterising and differentiating dysplastic nodules (DN) and hepatocellular carcinoma (HCC) in the cirrhotic liver by correlating the results with pathological findings on the explanted liver.

Material and methods

MR imaging was used to study the liver of 400 cirrhotic patients awaiting liver transplantation, 31 of whom were selected to receive a liver. Of these 31 patients, we included in the study 22 patients (mean age 53 years; range 46–57 years) who underwent liver transplantation within 12–24 h after MR examination. Patients were studied with a 1.5-T device, and scans were acquired before and after the administration of paramagnetic contrast material. For every lesion, we recorded signal intensity on unenhanced baseline T1- and T2-weighted images and enhancement pattern after SPIO administration. Histological examination of the entire liver provided the definitive diagnosis of the lesions.

Results

Histological examination identified 59 lesions: 14 HCC, 4 HCC-DN, 39 DN, and 2 cystoadenomas. Among the 14 HCC, three were well differentiated, eight were moderately differentiated and three were poorly differentiated. Of the 39 DN, 28 were low-grade and 11 high-grade lesions. Unenhanced baseline MR imaging correctly identified and characterised 20 lesions, equal to 33.90% of all lesions: 6 HCC, 12 DN and 2 DN with a subfocus of HCC. SPIO-enhanced MR imaging showed greater sensitivity detecting and characterising 45 lesions, equal to 76.27% of all lesions identified at histology: 14 HCC, 27 DN and 4 DN with subfocus of HCC. SPIO administration improved the sensitivity of MR imaging in lesion detection and characterisation by 42.37%. False negative results with SPIO-enhanced MR imaging occurred in 12 DN (31%), which histological examination revealed to be low-grade DN with a diameter <1 cm.

Conclusions

SPIO-enhanced MR imaging proved to be of value in detecting and characterising lesions in the cirrhotic liver, allowing differentiation of DN from HCC and providing an early diagnosis of neoplastic degeneration of DN.     

Hepatocellular carcinoma in cirrhotic patients: prospective comparison of US, CT and MR imaging

Objectives

To prospectively compare the diagnostic performance of ultrasound (US), multidetector computed tomography (MDCT) and contrast-enhanced magnetic resonance imaging (MRI) in cirrhotic patients who were candidates for liver transplantation.

Methods

One hundred and forty consecutive patients with 163 hepatocellular carcinoma (HCC) nodules underwent US, MRI and MDCT. Diagnosis of HCC was based on pathological findings or substantial growth at 12-month follow-up. Four different image datasets were evaluated: US, MDCT, MRI unenhanced and dynamic phases, MRI unenhanced dynamic and hepatobiliary phase. Diagnostic accuracy, sensitivity, specificity, PPV and NPV, with corresponding 95 % confidence intervals, were determined. Statistical analysis was performed for all lesions and for three lesion subgroups (<1 cm, 1-2 cm, >2 cm).

Results

Significantly higher diagnostic accuracy, sensitivity and NPV was achieved on dynamic + hepatobiliary phase MRI compared with US, MDCT and dynamic phase MRI alone. The specificity and PPV of US was significantly lower than that of MDCT, dynamic phase MRI and dynamic + hepatobiliary phase MRI. Similar results were obtained for all sub-group analyses, with particular benefit for the diagnosis of smaller lesions between 1 and 2 cm.

Conclusions

Dynamic + hepatobiliary phase MRI improved detection and characterisation of HCC in cirrhotic patients. The greatest benefit is for diagnosing lesions between 1 and 2 cm.

Key Points

? US, CT and MRI can all identify HCC in cirrhotic patients ? US has good sensitivity but suffers from false-positive findings ? Dynamic CT and MR have similar diagnostic performance for diagnosing HCC ? Dynamic + hepatobiliary phase MRI significantly improves detection and characterisation of HCC ? The greatest benefit is for the diagnosis of lesions between 1 and 2 cm     

Efficacy and Safety of Transarterial Radioembolization Versus Chemoembolization in Patients With Hepatocellular Carcinoma

Purpose

Intermediate-stage hepatocellular carcinoma (HCC) is usually treated with locoregional therapy using transarterial chemoembolization (TACE). Transarterial radioembolization (TARE) using β-emitting yttrium-90 integral to the glass matrix of the microspheres is an alternative to TACE. This retrospective case-control study compared the outcomes and safety of TARE versus TACE in patients with unresectable HCC.

Materials and Methods

Patients with unresectable HCC without portal vein thrombosis treated with TARE between 2005 and 2008 (n = 61) were retrospectively frequency-matched by age, sex, and liver dysfunction with TACE-treated patients (n = 55) in the Mayo Clinic Hepatobiliary Neoplasia Registry. Imaging studies were reviewed, and clinical and safety outcomes were abstracted from the medical records.

Results

Complete tumor response was more common after TARE (12 %) than after TACE (4 %) (p = 0.17). When complete response was combined with partial response and stable disease, there was no difference between TARE and TACE. Median survival did not differ between the two groups (15.0 months for TARE and 14.4 months for TACE; p = 0.47). Two-year survival rates were 30 % for TARE and 24 % for TACE. TARE patients received fewer treatments (p < 0.001). Fifty-nine (97 %) TARE patients received outpatient treatment. In contrast, 53 (98 %) TACE patients were hospitalized for ≥1 day (p < 0.001). Compared with TACE, TARE was more likely to induce fatigue (p = 0.003) but less likely to cause fever (p = 0.02).

Conclusion

There was no significant difference in efficacy between TARE and TACE. TARE patients reported more fatigue but had less fever than TACE patients. Treatment with TARE required less hospitalization than treatment with TACE. These findings require confirmation in randomized trials.     

Does Establishing a Safety Margin Reduce Local Recurrence in Subsegmental Transarterial Chemoembolization for Small Nodular Hepatocellular Carcinomas?

Objective

To test the hypothesis that a safety margin may affect local tumor recurrence (LTR) in subsegmental chemoembolization.

Materials and Methods

In 101 patients with 128 hepatocellular carcinoma (HCC) nodules (1-3 cm in size and ≤ 3 in number), cone-beam CT-assisted subsegmental lipiodol chemoembolization was performed. Immediately thereafter, a non-contrast thin-section CT image was obtained to evaluate the presence or absence of intra-tumoral lipiodol uptake defect and safety margin. The effect of lipiodol uptake defect and safety margin on LTR was evaluated. Univariate and multivariate analyses were performed to indentify determinant factors of LTR.

Results

Of the 128 HCC nodules in 101 patients, 49 (38.3%) nodules in 40 patients showed LTR during follow-up period (median, 34.1 months). Cumulative 1- and 2-year LTR rates of nodules with lipiodol uptake defect (n = 27) and those without defect (n = 101) were 58.1% vs. 10.1% and 72.1% vs. 19.5%, respectively (p < 0.001). Among the 101 nodules without a defect, the 1- and 2-year cumulative LTR rates for nodules with complete safety margin (n = 52) and those with incomplete safety margin (n = 49) were 9.8% vs. 12.8% and 18.9% vs. 19.0% (p = 0.912). In multivariate analyses, ascites (p = 0.035), indistinct tumor margin on cone-beam CT (p = 0.039), heterogeneous lipiodol uptake (p = 0.023), and intra-tumoral lipiodol uptake defect (p < 0.001) were determinant factors of higher LTR.

Conclusion

In lipiodol chemoembolization, the safety margin in completely lipiodolized nodule without defect will not affect LTR in small nodular HCCs.     

Switching the Loaded Agent from Epirubicin to Cisplatin: Salvage Transcatheter Arterial Chemoembolization with Drug-eluting Microspheres for Unresectable Hepatocellular Carcinoma

Purpose

There is no consensus on switching anticancer agents loaded onto drug carriers in transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). This study aimed to evaluate the safety and clinical outcomes of TACE with cisplatin-loaded microspheres (CLM-TACE) in HCC patients refractory to TACE with epirubicin-loaded microspheres (ELM-TACE).

Methods

Between February 2008 and June 2010, 85 patients with unresectable HCC refractory to ELM-TACE were enrolled to undergo CLM-TACE. The number of ELM-TACE sessions until judgment of resistance ranged from 1 to 4 (median, 2.1). CLM-TACE was performed using 50?C100-??m superabsorbent polymer microspheres loaded with 1?mg cisplatin/1?mg microspheres together with hepatic arterial infusion of 25?mg cisplatin and 500?mg 5-fluorouracil per patient. Tumor responses were evaluated by computed tomography according to the European Association for the Study of the Liver criteria.

Results

The median number of CLM-TACE treatment sessions was 1.8 (range, 1?C5), and the mean total dose of cisplatin per session was 42.8?mg (range, 30.0?C59.0). After 6?months, 3 (3.5%) patients achieved complete response, 31 (36.5%) had partial response, 15 (17.6%) had stable disease, and 36 (42.4%) had progressive disease. The median overall survival and time to treatment failure after initial CLM-TACE were 13.3 and 7.2?months, respectively. Overall, 9.4% of patients experienced grade 3/4 adverse events.

Conclusion

Switching the loaded agent from epirubicin to cisplatin is a safe, well-tolerated, and efficacious treatment strategy for salvage TACE with drug-eluting microspheres in HCC patients refractory to ELM-TACE.     

A radiological-pathological correlation of hepatocellular carcinoma (HCC).

The histological distribution of lipiodol within hepatocellular carcinoma (HCC) was correlated with that seen on computed tomography (CT), arteriography and high resolution plain films of 15 resected specimens. By means of special stains, the arterially administered lipiodol was shown to be maximally distributed at the periphery of large tumours and nodules. The centre of large lesions often remained unopacified. In multinodular tumours some nodules were heavily stained while others contained little or no contrast medium. In small tumours there was a more uniform distribution. In large tumours, those areas where there are large arteries (and slow flow) contained little or no lipiodol. There was also no consistent match of areas of angiographic blush with lipiodol deposition. The lipiodol patterns were poorly shown by CT when compared with high resolution films taken on a mammography unit. We conclude from this study that lipiodol on its own as an embolic agent or as a chemotherapeutic carrier has great limitations because of its peripheral and otherwise haphazard distribution in large tumours. However, such treatments might be more effective in small tumours where a greater concentration of lipiodol is likely. Nevertheless, lipiodol staining of tumours remains a useful diagnostic aid as small HCC can be difficult to visualize both on arteriography and conventional CT.     

The incidence of contrast-induced nephropathy (CIN) following transarterial chemoembolisation (TACE) in patients with hepatocellular carcinoma (HCC)

Purpose

The purpose of this retrospective study was to investigate the incidence of contrast-induced nephropathy (CIN) caused by transarterial chemoembolisation (TACE) in patients with hepatocellular carcinoma (HCC).

Materials and Methods

One hundred forty-one patients treated between 2005 and 2008 undergoing 305 consecutive sessions of TACE were enrolled. CIN was defined as an increase in the serum creatinine level of more than 0.5 mg/dl or more than 25 % from baseline within 3 days after TACE without any other identifiable cause of acute kidney injury.

Results

CIN by the present definition was observed after 2.6 % of the TACE sessions. No patient showed clinical signs or symptoms of acute renal failure, or required haemodialysis. None of the patients with an estimated glomerular filtration rate of <60 ml/min/1.73 m² developed CIN.

Conclusion

The present study suggests that TACE is a relatively safe procedure in terms of the risk of CIN under vigorous periprocedural hydration and that the incidence of CIN is comparable to that of AKI associated with intravenous CM administration.

Key points

? CIN would be lower for non-coronary arterial intervention than for coronary intervention. ? The present study suggests that the CIN rates following TACE are low. ? The incidence of CIN is comparable to that after intravenous CM administration.     

Origins of Feeding Arteries of Hepatocellular Carcinoma Located Near the Umbilical Fissure of the Left Hepatic Lobe: Angiographic Evaluation

Purpose

To analyze the origins of the feeding arteries of hepatocellular carcinomas (HCCs) near the umbilical fissure of the left hepatic lobe.

Methods

Twenty-eight HCCs with a mean?±?SD tumor diameter of 3.4?±?1.0?cm (range 1–4.4?cm) in contact with the right or left side of the umbilical fissure were treated by superselective transcatheter arterial chemoembolization (TACE). The origins of the tumor-feeding arteries were analyzed with arteriograms and computed tomography or cone-beam computed tomography images obtained during and 1?week after TACE.

Results

Twenty-one HCC lesions were located in segment 3 and seven were located in segment 4. Of 21 tumors in segment 3, 13 (61.9%) were supplied by the lateral inferior subsegmental artery (A3), three (14.3%) by the medial subsegmental artery (A4), three (14.3%) by both A4 and A3, one (4.8%) by a branch arising from the left lateral hepatic artery, and one (4.8%) by a branch of the right gastric artery. In particular, all tumor-feeding branches arising from A4 were the first branch of A4. Of seven tumors in segment 4, four (57.1%) were supplied by A4 and three (42.9%) by A3. In particular, all tumor-feeding branches arising from A3 were the first branch of A3.

Conclusion

This study demonstrates crossover blood supply to HCC lesions located near the umbilical fissure, in addition to direct feeding from a separate branch. In particular, the first branch of the opposite subsegmental artery may feed tumors when crossover blood supply is present.     

Local Therapeutic Results of Computed Tomography-Guided Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: Results of 265 Tumors in 79 Patients

Purpose To elucidate the local therapeutic results of computed tomography (CT)-guided transcatheter arterial chemoembolization (TACE) as initial treatment for hepatocellular carcinoma (HCC), and to verify factors which affect local therapeutic results. Methods From 1992 to 2002, 265 tumors of 79 HCC patients were treated by 139 sessions of CT-guided TACE as initial treatment. Among these 265 tumors, 182 constituted multiple new lesions, and the remaining 83 tumors were single new lesions. Local recurrence was retrospectively ascertained on follow-up CT images obtained after TACE. Results The overall local recurrence-free rates (LR-FRs) after a single TACE session at 6, 12, and 36 months were 67%, 49%, and 28%; those of the single new lesions were 80%, 66%, and 32%; and those of tumors with complete lipiodol accumulation were 82%, 68%, and 41%, respectively. LR-FRs of tumors of the single new lesions, and those of tumors with complete lipiodol accumulation, were significantly higher than the LR-FRs of multiple new lesions and tumors with incomplete lipiodol accumulation, respectively. For single new lesions ≤4 cm and the tumors that were one of multiple new lesions, there were no significant differences in the LR-FRs regarding the number of TACE sessions on the basis of patient, tumor location, or tumor size. Conclusion Local therapeutic results of single new lesions were better than those of multiple new lesions, and the local therapeutic effect of TACE was not affected by the number of treatments on the basis of patient, tumor location, or tumor size.     

Gadoxetic acid-enhanced MRI for hepatocellular carcinoma and hypointense nodule observed in the hepatobiliary phase

Purpose

The aim of our study was to evaluate the diagnostic accuracy of gadoxetic acid-enhanced magnetic resonance (MR) imaging both in the detection of hepatocellular carcinoma (HCC) and precancerous lesions and in the assessment of their evolution.

Materials and methods

A retrospective study was undertaken on 56 patients with chronic liver disease and suspected liver lesions. We evaluated the number, size and signal intensity of the nodules on dynamic and hepatobiliary MR images. Follow-up studies were carried out every 3 months. Statistical analysis was performed using the Fisher’s exact test.

Results

A total of 120 nodules were identified in 41 patients. Of these, 92/120 nodules (76.6 %; mean diameter 18.4 mm) showed the typical HCC vascular pattern: 90/92 nodules appeared hypointense and 2/92 were hyperintense on hepatobiliary phase images. An additional 28/120 hypointense, nonhypervascular nodules (23.3 %; mean diameter 11 mm) were detected on hepatobiliary phase images, 15 of which showed hypointensity also on the equilibrium phase images. During the 3- to 12-month follow-up, 14/28 nodules (mean diameter 13.3 mm) developed the typical vascular pattern of HCC.

Conclusions

Gadoxetic acid-enhanced MR imaging is useful for detecting HCC as well as hypovascular nodules with potential progression to HCC. Lesions measuring more than 10 mm in diameter are at higher risk of developing into HCC (p = 0.0128).