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Appraisal of Long-Term Outcomes of Liver-Directed Concurrent Chemoradiotherapy for Hepatocellular Carcinoma with Major Portal Vein Invasion
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Appraisal of Long-Term Outcomes of Liver-Directed Concurrent Chemoradiotherapy for Hepatocellular Carcinoma with Major Portal Vein Invasion
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Transarterial chemoembolization (TACE) using doxorubicin-eluting beads (DEBs) have been introduced as a novel device which ensures more sustained and tumor-selective drug delivery and permanent embolization compared to conventional TACE with lipiodol. Studies highlighting the use of TACE with DEBs for the treatment of hepatocellular carcinoma (HCC) have shown similar or better results compared to conventional TACE with lipiodol. TACE with DEBs is increasingly being performed interchangeably with conventional TACE. This review assessed the characteristics, clinical outcomes and future direction of TACE with DEBs compared to conventional TACE.
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The therapeutic effect of transarterial chemoembolization (TACE) against hepatocellular carcinoma (HCC) is usually assessed using multidetector computed tomography (MDCT). However, dense lipiodol depositions can mask the enhancement of viable HCC tissue in MDCT. Contrast-enhanced ultrasonography (CEUS) could be effective in detecting small areas of viability and patency in vessels. We investigated whether arterial enhancement in CEUS after treatment with TACE can be used to detect HCC viability earlier than when using MDCT.
Twelve patients received CEUS, MDCT, and gadoxetic-acid-enhanced dynamic magnetic resonance imaging (MRI) at baseline and 4 and 12 weeks after TACE. The definition of viable HCC was defined as MRI positivity after 4 or 12 weeks.
Eight of the 12 patients showed MRI positivity at 4 or 12 weeks. All patients with positive CEUS findings at 4 weeks (n=8) showed MRI positivity and residual viable HCC at 4 or 12 weeks. Five of the eight patients with positive CEUS findings at 4 weeks had negative results on the 4-week MDCT scan. Four (50%) of these eight patients did not have MRI positivity at 4 weeks and were ultimately confirmed as having residual HCC tissue at the 12-week MRI. Kappa statistics revealed near-perfect agreement between CEUS and MRI (κ=1.00) and substantial agreement between MDCT and MRI (κ=0.67).
In the assessment of the response to TACE, CEUS at 4 weeks showed excellent results for detecting residual viable HCC, which suggests that CEUS can be used as an early additive diagnosis tool when deciding early additional treatment with TACE.
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The predictive role of contrast-enhanced ultrasonography (CEUS) before performing transarterial chemoembolization (TACE) has not been determined. We assessed the possible predictive factors of CEUS for the response to TACE.
Seventeen patients with 18 hepatocellular carcinoma (HCC) underwent TACE. All of the tumors were studied with CEUS before TACE using a second-generation ultrasound contrast agent (SonoVue®, Bracco, Milan, Italy). The tumor response to TACE was classified with a score between 1 and 4 according to the remaining enhancing-tumor percentage based on modified response evaluation criteria in solid tumors (mRECIST): 1, enhancing tumor <25%; 2, 25%≤enhancing tumor<50%; 3, 50%≤enhancing tumor<75%; and 4, enhancing tumor≥75%). A score of 1 was defined as a "good response" to TACE. The predictive factors for the response to TACE were evaluated during CEUS based on the maximum tumor diameter, initial arterial enhancing time, arterial enhancing duration, intensity of arterial enhancement, presence of a hypoenhanced pattern, and the feeding artery to the tumor.
The median tumor size was 3.1 cm. The distribution of tumor response scores after TACE in all tumors was as follows: 1, n=11; 2, n=4; 3, n=2; and 4, n=1. Fifteen tumors showed feeding arteries. The presence of a feeding artery and the tumor size (≤5 cm) were the predictive factors for a good response (
The presence of a feeding artery and a tumor size of less than 5 cm were the predictive factors for a good response of HCC to TACE on CEUS.
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The aim of this study was to determine the relationship between serum CRP levels and the prognosis of hepatocellular carcinoma (HCC) patients.
HCC patients who underwent the first session of transcatheter arterial chemoembolization (TACE) between January 2005 and December 2009 (n=211) were analyzed retrospectively. The patients were divided into two groups: high C-reactive protein (CRP; ≥1 mg/dL, n=51) and low CRP (<1 mg/dL, n=160). They were followed for a mean of 22.44 months and their clinicoradiological variables and overall survival were compared.
There were significant differences between the two groups in regard to tumor type, tumor-progression-free survival, 10-month mortality, white blood cell (WBC) count, tumor size, and TNM stage. Multivariate analysis revealed that a high serum CRP level was independently associated with tumor size and tumor type. Subgroup analysis of CRP groups according to tumor size demonstrated that a high serum level of CRP was significantly associated with poorly defined (diffuse) tumor type in the tumor size <5 cm group [hazard ratio (HR)=4.81,
A high serum CRP level is associated with large tumors and a poorly defined tumor type, and is significantly associated with 10-month mortality in patients with large HCC (size ≥5 cm) who undergo TACE.
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Necrotizing pancreatitis is one of the rare complications of transcatheter arterial chemoembolization (TACE). Necrotizing pancreatitis after TACE may result from the development of ischemia caused by regurgitation of embolic materials into the vessels supplying the pancreas. We report a case of post-TACE necrotizing pancreatitis with abscess formation in a patient with hepatocellular carcinoma. The patient had suffered hepatic artery injury due to repetitive TACE; during his 25th TACE procedure he had submitted to selective catheterization of the feeding vessel from the dorsal pancreatic artery with a cytotoxic agent and Gelfoam particles. The patient complained of abdominal pain after the TACE procedure, and a CT scan led to a diagnosis of necrotizing pancreatitis with abscess formation. The pancreatic abscess progressed despite general management of the pancreatitis, including antibiotics. Percutaneous catheter drainage was performed, and the symptoms of the patient improved.
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Reports of metastatic hepatocellular carcinoma (HCC) without a primary liver tumor are rare. Here we present a case of isolated HCC that had metastasized to the pelvic bone without a primary focus. A 73-year-old man presented with severe back and right-leg pain. Radiological examinations, including computed tomography (CT) and magnetic resonance imaging (MRI), revealed a huge mass on the pelvic bone (13×10 cm). He underwent an incisional biopsy, and the results of the subsequent histological examination were consistent with metastatic hepatocellular carcinoma. The tumor cells were positive for cytokeratin (AE1/AE3), hepatocyte paraffin 1, and glypican-3, and negative for CD56, chromogranin A, and synaptophysin on immunohistochemical staining. Examination of the liver by CT, MRI, positron-emission tomography scan, and angiography produced no evidence of a primary tumor. Radiotherapy and transarterial chemoembolization were performed on the pelvic bone, followed by systemic chemotherapy. These combination treatments resulted in tumor regression with necrotic changes. However, multiple lung metastases developed 1 year after the treatment, and the patient was treated with additional systemic chemotherapy.
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It has been shown that the drug-eluting beads loaded with doxorubicin (DEBDOX) are effective for the treatment of hepatocellular carcinoma (HCC). However, the optimal safety and efficacy still remain to be established by using various bead sizes, doxorubicin doses, and the degree of stasis.The aim of this study was to determine the optimal safety and efficacy of DEBDOX in the treatment of HCC.
Analysis of a 503-patient prospective, multicenter, multinational Bead Registry Database from 2007 to 2010 identified 206 patients who had been treated for HCC with DEBDOX. Primary endpoints were to compare safety, tolerance, response rates, and overall survival based on bead size (100-300, 300-500, 500-700, and 700-900 µm), number of vials, doxorubicin dose, and degree of stasis.
In total, 206 patients underwent 343 treatments. The use of all four bead sizes was similar based on Child-Pugh class and Okuda stage, with a significantly higher use (50%) of beads of size 100-300 µm in patients with portal vein thrombosis (
Bead size and dose may vary according to disease distribution. Smaller beads offer the opportunity for repeated treatments, a larger cumulative dose delivery, a lesser degree of complete stasis, and fewer adverse events.
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Hepatocellular carcinoma (HCC) in the caudate lobe remains one of the most intricate locations where various treatments tend to pose problems with regard to the optimal approach. Surgical resection has been regarded as the most effective treatment; however, isolated resection of the caudate lobe is strenuous and associated with a high rate of early recurrence. Percutaneous ablation might be technically difficult or impossible to perform due to the deep location of tumors and adjacent large vessels. Treatment with drug-eluting beads (DEB) can potentially enhance the therapeutic efficacy for patients with unresectable HCC by drawing on the slower, more consistent drug delivery process. We described a case of a 62-year-old man with HCC in the caudate lobe who was successfully treated by DEB.
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Transarterial chemoembolization (TACE) improves the survival of patients with unresectable hepatocellular carcinoma (HCC) and has been recommended as a first-line therapy for nonsurgical patients with large or multifocal HCC. The long-term outcome of HCC patients receiving TACE prior to hepatic resection is uncertain.
Between January 1997 and December 2007, 1,530 patients underwent hepatic resection for HCC at our center. Thirty-two patients received 1~12 sessions of TACE followed by surgical resection (TACE-surgery group). Their overall and recurrence-free survival rates were compared with those of 64 age- and sex-matched controls who underwent surgery only (surgery group). Overall and recurrence-free survival rates were analyzed.
The 1-, 2-, and 5-year overall survival rates did not differ significantly between the TACE-surgery group and the surgery group (78%, 60%, and 26%, respectively, vs. 97%, 83%, and 45%, respectively;
HCC patients who underwent TACE before resection appear to have overall survival rates that are comparable to those without preoperative therapy, although recurrence rates appear to be higher in patients with TACE.
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Transarterial chemoembolization (TACE) has long been used as a palliative therapy for unresectable hepatocellular carcinoma (HCC). High-dose hepatic arterial infusion chemotherapy (HAIC) has showed favorable outcomes in patients with intractable, advanced HCC. The aim of this study was to compare the effectiveness and safety of high-dose HAIC and conventional TACE using doxorubicin for advanced HCC.
The high-dose HAIC group comprised 36 patients who were enrolled prospectively from six institutions. The enrollment criteria were good liver function, main portal vein invasion (including vascular shunt), infiltrative type, bilobar involvement, and/or refractory to prior conventional treatment (TACE, radiofrequency ablation, or percutaneous ethanol injection), and documented progressive disease. Patients received 5-fluorouracil (500 mg/m2 on days 1~3) and cisplatin (60 mg/m2 on day 2 every 4 weeks) via an implantable port system. In the TACE group, 31 patients with characteristics similar to those in the high-dose HAIC group were recruited retrospectively from a single center. Patients underwent a transarterial infusion of doxorubicin every 4~8 weeks.
Overall, 6 patients (8.9%) achieved a partial response and 20 patients (29.8%) had stable disease. The
objective
response rate (complete response+partial response) was significantly better in the high-dose HAIC group than in the TACE group (16.7% vs. 0%,
High-dose HAIC appears to improve the tumor response and survival outcome compared to conventional TACE using doxorubicin in patients with intractable, advanced HCC.
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