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The targeting and sustained release characteristics of cytotoxic drug-loaded protein microspheres may prove useful in the therapeutic chemoembolization of solid tumours. Because biodegradation rate of embolized particles will influence rate of incorporated drug release and duration of exposure, this parameter was studied for microspheres (10-30 microns mean diam.) prepared from the proteins albumin and casein, that we have previously used as carriers for doxorubicin. As a measure of microsphere loss in-vivo the radionuclide 125I was chosen because it can be covalently bound to proteins and also homogeneously distributed throughout the matrix. Radiolabelled microspheres were administered to rats both intravenously (lung as target organ, 1.4-2.2 mg/100 g) and via the hepatic artery (liver as target organ, 0.4-0.8 mg/100 g). In both cases it was observed that the casein system biodegraded more slowly than the albumin in-vivo. Thus, time taken for loss of 50% of embolized microspheres from lung was: albumin 2.0 days; casein 3.5 days and from liver:albumin 3.6 days; casein 6.8 days. Microsphere "debris" did not markedly accumulate in other organs. In-vitro experiments showed that microspheres were stable in serum and that albumin microspheres were not innately more sensitive to enzymic digestion than casein. The results may be useful in estimating duration of exposure of target organs to drug-loaded microsphere systems prepared from these proteins.
PURPOSE: Identifying a special subgroup of hepatocellular carcinoma (HCC) patients who may benefit from transcatheter arterial chemoembolization (TACE) when compared with the standard treatment of hepatic resection (HR) warrants research in Asian countries. PATIENTS AND METHODS: From January 1993 to December 1994, 182 patients with operable HCC (Child-Pugh class A and International Union Against Cancer [UICC] stage T1-3N0M0) were enrolled. After initial TACE and lipiodol computed tomography, 91 received HR and 91, who refused the operation, received repeated sessions of TACE. After stratification according to the tumor stage (UICC and Cancer of the Liver Italian Program [CLIP]) and lipiodol retention pattern, the survival rates of the two treatment groups were compared. The median follow-up period was 83 months. RESULTS: As of December 31, 2000, 48 patients who underwent HR and 68 patients who underwent TACE had died. In a subgroup analysis according to tumor stage, the HR group survival rate was significantly higher than the TACE group in both UICC T1-2N0M0 (P =.0058) and CLIP 0 (P =.0027) subgroups. However, there was no significant difference in either UICC T3N0M0 (P =.7512) or CLIP 1-2 (P =.5366) subgroups. Even in patients with UICC T1-2N0M0 HCC, when lipiodol was compactly retained, the survival rate of the HR group was comparable to that of the TACE group (P =.0596). CONCLUSION: TACE proved to be as effective as HR in the subpopulations with UICC T3N0M0 or CLIP 1-2 HCC and adequate liver function, and even with UICC T1-2N0M0 HCC when lipiodol was compactly retained in the tumor. In such cases, the choice of treatment modality between TACE and HR may be left to the patient's preference.
BACKGROUND & OBJECTIVE: Many clinic data showed that it is difficult to control primary liver carcinoma (PLC) by transcatheter arterial chemoembolization (TACE) alone due to existence of double blood supply of liver by hepatic artery and portal vein. This study was designed to evaluate the efficacy of transcatheter arterial chemoembolization combined with portal venous chemoembolization (PVCE) in the treatment of moderate and advanced stages of PLC. METHODS: Fifty-eight cases of moderate and advanced stages of PLC were treated with a combination of TACE and PVCE (TACE/PVCE group) and 118 patients with moderate and advanced stages of PLC were treated with TACE alone (TACE group). RESULTS: (1)The total response rates were 86.2% in TACE+PVCE group and 69.5% in TACE group. The remarkable response rates were 31.0 % in TACE/PVCE group and 13.6% in TACE group (P< 0.05). (2)The half-year survival rates were 93.1% in TACE/PVCE group and 72.0% in TACE group (P< 0.05). The 1-year survival rates were 43.1% in TACE/PVCE group and 51.7% in TACE group. The 4-year survival rates were 6.9% in TACE/PVCE group and 5.1% in TACE group (P >0.05). (3) Side effects included fever, bellyache, white blood cell drop, hypohepatia, jaundice,and ascites. The degree of liver damage was positively associated with the amount of iodized oil. CONCLUSION: The combination of TACE and PVCE appears to promote the short-term efficacy but not the long-term efficacy, compared with TACE alone for patients with moderate and advanced PLC.
BACKGROUND: The resection rate of primary liver tumor in China is only about 20%. A lot of patients with moderate and advanced liver tumor may lose the chance of operation. The objective of present research was to study the efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous injection of chemical agents and acetic acids in the treatment of patients with primary liver cancer (PLC). METHODS: Thirty-three patients with middle and advanced stage of PLC were divided into two groups: percutaneous injection of chemical agents and acetic acids (15 patients, group A) and TACE (18 patients, group B). RESULTS: Tumor diameter and serum AFP level reduced to 86.6% and 83.3% in group A, and 55.5% and 40% in group B, respectively. There was significant difference between the two groups (P<0.01). The 1, 2, 3, 4-year survival rates of group A were 96.7%, 86.6%, 51.3%, 33.3%, respectively and in group B were 66.7%, 44.4%, 16.7%, 0%, respectively (P<0.01). CONCLUSION: TACE combined with percutaneous injection of chemical agents and acetic acids is efficacious to increase the survival rate of patients with PLC.
HISTORY AND CLINICAL FINDINGS: A 73-year-old previously healthy woman presented with recurrent weakness, vertigo and perioral paresthesia of 3 months' duration. Physical examination on admission was unremarkable and revealed a patient in good condition. INVESTIGATIONS: Recurrent episodes of fasting hypoglycemia let us to proceed with a fasting test. The test was stopped after 24 hours when the patient became presyncopal and was found to have a blood sugar value of 2.2 mmol/l (accompanied by inadequately increased values for proinsulin, insulin and C-peptide). Ultrasound and computertomography of the abdomen showed a huge inhomogeneous mass in the tail of pancreas and multiple lesions in the liver, respectively. Core needle biopsies revealed typical histopathological findings of a neuroendocrine carcinoma. TREATMENT AND COURSE: Eight cycles of chemotherapy were given using streptozotocin/doxorubicin for three cycles and streptozotocin/5-fluorouracil for the remaining therapy over a period of 16 months resulting in a reduction in size of liver metastases and improvement of symptoms. Following 6 months without any therapy new episodes of severe hypoglycemia and progression of the liver metastases occurred. Despite seven further cycles of chemotherapy and additional treatment with diazoxide/octreotide the patient remained hypoglycemic and continuous glucose infusions became necessary. Therefore, chemoembolization of the liver with streptozotocin/5-fluorouracil and lipiodol-emulsion was performed. This resulted in a significant improvement of symptoms and the patient could subsequently be discharged. The patient died 4 months later. CONCLUSION: Chemoembolization is an effective possibility in the palliative treatment of advanced malignant insulinoma.
PURPOSE: To evaluate the usefulness of power Doppler sonography (PDS) in assessing the therapeutic effect of transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). MATERIAL AND METHODS: TACE was performed in 43 patients (48 lesions) with HCC. All patients were examined with both PDS and color Doppler sonography (CDS) to assess the therapeutic results 1 week after TACE. Follow-up hepatic angiography was performed in 39 patients 3-4 months after TACE and then CT after iodized oil reinjection was also performed 3-4 weeks after a repeat TACE; in the remaining 4 patients, hepatectomy was performed within one month after chemoembolization and histologic study was undertaken to confirm the Doppler findings. RESULTS: Determination of therapeutic results with PDS and CDS were in agreement with those of follow-up findings in 37 and 29 of the 48 lesions, respectively. There was a significant difference in overall accuracy (p=0.038) between PDS and CDS results. CONCLUSION: PDS is more effective than CDS for evaluating changes in tumor vascularity after TACE. PDS may also replace angiography in assessing the therapeutic effects of TACE for HCCs, except in deep-seated areas.
The objective of this study was to evaluate the therapeutic effectiveness of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI). Seventeen patients with histopathologically proven HCC were included in this study. All patients underwent MR examinations with conventional T1- and T2-weighted images, gadolinium-enhanced images, and DSC-MRI before TACE treatment. Hepatic blood volume (HBV) maps were reconstructed from the time-intensity curves. The same MRI sequences and techniques were repeated 24 h and 6 weeks after TACE. Serial changes in tumor perfusion on HBV maps were correlated with vascularity in hepatic angiography. All tumors were hypointense on T1-weighted images and hyperintense on T2-weighted images. Heterogeneous enhancement was observed in all tumors before and immediately after TACE. Hyperperfusion was noted in most of the tumors on HBV map before TACE and moderate to marked hypoperfusion following TACE. The degree of tumor perfusion on HBV map correlated well with the vascularity in angiography. In conclusion, the noninvasive nature of DSC-MRI is useful to evaluate the effectiveness of TACE. Invasive procedures, such as angiography, are seldom necessary.
We report the results of a multicenter study on the diagnosis and interventional therapy of hepatocellular carcinoma (HCC). The first aim--diagnosis--was to evaluate the sensitivity of 4 imaging techniques, namely ultrasonography (US), Computed Tomography (CT), digital arteriography (DSA) and Lipiodol CT (LCT), in HCC detection. The accuracy of these techniques was also investigated in tumor staging, which is important for treatment planning. Two hundred ninety patients underwent this imaging protocol. The patients were classified by tumor spread into three groups, namely group 1 (single HCCs < 5 cm), group 2 (multifocal HCCs with max. 3 nodules or tumor volume < 80 cc), group 3 (multifocal HCCs with more than 3 nodules and/or tumor volume > 80 cc). US and CT diagnosed more cases as group 1 and fewer cases as group 3 than DSA and LCT; the latter two techniques gave a similar classification. With LCT as the gold standard, US and CT understaged 27.9% and 26.5% of cases, respectively. Even though LCT is known to have 53% sensitivity, it is currently the most sensitive preoperative investigation and therefore the best tool for treatment planning. In surgical patients, however, intraoperative US, with its nearly 100% sensitivity, is suggested. The second aim--treatment--consisted in assessing the therapeutic efficacy of intraarterial chemoembolization (CEAT) versus percutaneous ethanol injection (PEI) in non advanced HCC and of CEAT versus no treatment (NT) in advanced HCC. Treatment efficacy was evaluated with the following randomized protocols: PEI versus CEAT in group 1, PEI versus CEAT in group 2 and CEAT versus NT in group 3. The data were analyzed relative to 215 patients for 6 to 30 months. The Kaplan-Meier method was used to calculate survival rates, which were, at 24 and 30 months, 72% and 72% for PEI and 72% and 52% for CEAT in group 1, 52% and 28% for PEI and 70% and 50% for CEAT in group 2 and finally 30% and 20% for NT and 45% and 30% for CEAT in group 3. In group 1, PEI appeared markedly superior to CEAT. In group 2, the difference between PEI and CEAT was not statistically significant; the results in this group indicate that CEAT should be considered when three nodules are present because of PEI invasiveness in these cases. In group 3, CEAT results were definitely better in the first two years, but there was no difference with NT patients at the end of the third year. Therefore, CEAT is indicated in advanced HCC because it improves the survival rate in the first 24 months. After this period, the survival time is not modified by treatment.
OBJECTIVE: We evaluated the usefulness of contrast-enhanced harmonic wideband gray-scale sonography in the assessment of the therapeutic effects of transcatheter arterial chemoembolization in patients with hepatocellular carcinoma and compared the performance of this imaging modality with the histologic findings for the patients. SUBJECTS AND METHODS: Twenty-nine patients with 29 hepatocellular carcinoma lesions were examined. Tumor vascularity was evaluated before and 7 days after transcatheter arterial chemoembolization with contrast-enhanced harmonic wideband gray-scale sonography performed after injection of the contrast agent Levovist. Several biopsy specimens were obtained from the evaluated lesions, and the histologic findings were compared with the results of contrast-enhanced sonography. RESULTS: Contrast-enhanced harmonic wideband gray-scale sonography performed after transcatheter arterial chemoembolization showed tumor vascularity in 16 of the 29 lesions, but none in the other 13 lesions. At histologic examination, 13 of the 16 lesions with tumor vascularity had residual tumor revealed, and the 13 lesions without tumor vascularity were found to have no histologically evident tumor residue, although three of these lesions showed tumor progression detected on CT during a 9- to 12-month follow-up period. Contrast-enhanced harmonic wideband gray-scale sonographic images were compared with the histologic findings as the gold standard, and the sensitivity and specificity of these images for discerning viable and nonviable hepatocellular carcinoma after transcatheter arterial chemoembolization were 100% and 81%, respectively. CONCLUSION: Contrast-enhanced harmonic wideband gray-scale sonography is potentially useful for evaluating the therapeutic effects of transcatheter arterial chemoembolization on hepatocellular carcinoma.
Arterial chemoembolization using degradable starch microspheres and adriamycin was combined with hyperthermia to treat advanced liver cancer. The prolonged peak adriamycin level in hepatic venous blood suggested that the drug persisted for longer in the liver after injection containing microspheres. Heating efficiency was increased more in tumor tissue than in normal liver tissue after embolization. This combined therapy was performed in eight patients with advanced liver cancer and was effective in three (complete or partial remission). The mean survival time was 25 weeks and there were no severe side effects. This combined therapy may be useful for liver cancer.
OBJECTIVE: Our goal was to evaluate the usefulness of multisection dynamic MRI with gadopentetate dimeglumine in the assessment of the therapeutic efficacy of transcatheter arterial chemoembolization (TAE) with iodized oil for hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: Findings on multisection dynamic MRI images were compared with gross appearance and histologic findings in 13 patients with HCCs after TAE with iodized oil. Arterial dominant phase images of the entire liver were obtained 20 s after the start of administration of gadopentetate dimeglumine. RESULTS: In 3 of the 13 patients, no enhancing areas within the tumors were detected. In the remaining 10 patients, enhancing portions were detected within the tumor on arterial dominant phase images. Histologically, viable tumor cells were present in the rapidly enhancing portions, while necrotic tissues were present in nonenhancing areas, irrespective of the accumulation of iodized oil on CT scans. However, in one patient in whom no enhancing portion was seen in the tumor, a small number of viable tumor cells within the capsule were identified on pathologic examination. CONCLUSION: Multisection dynamic MRI is helpful for evaluating the therapeutic efficacy of TAE with iodized oil for HCCs by revealing the hemodynamics of the tumor irrespective of accumulation of iodized oil.
An emulsion of iodized oil and doxorubicin hydrochloride was intraarterially injected in 27 patients with encapsulated single nodular hepatocellular carcinoma (HCC). Computed tomography (CT) was performed 1-3 weeks after injection, and the lesions were resected 1-4 weeks thereafter. The percentages of tumor necrosis were evaluated in cut surfaces of resected specimens and were compared with the findings at iodized-oil CT. Six tumors with complete intratumor retention of iodized oil had 98% necrosis, and 21 tumors with incomplete retention had 64% necrosis. Two tumors with complete retention of iodized oil in the surrounding liver had 100% necrosis, while 16 tumors with partial retention and nine tumors without retention of iodized oil in surrounding liver had 74% and 62% necrosis, respectively. Complete retention of iodized oil in the tumor and surrounding liver demonstrated the best therapeutic effects. Evaluation of the pattern and distribution of iodized oil in the tumor and surrounding liver with iodized-oil CT is useful in the assessment of the therapeutic effects of transcatheter arterial embolization in encapsulated nodular HCCs.
Screening programs for patients with cirrhosis are designed to detect hepatocellular carcinoma at an early stage when effective treatment is feasible and may provide long-term survival benefits. However, only a minority of these patients will be considered candidates for liver transplantation or surgical resection and hence, most cases will be evaluated for other medical options. While systemic therapy has never been shown to bear a relevant antitumoral activity with an impact on survival, there are several locoregional options that can achieve a high rate of objective responses (this includes complete necrosis or partial reduction in tumor burden). Percutaneous ablation by any of the available methods (ethanol injection, radiofrequency, microwave, acetic acid injection, laser) is extremely useful in patients with small solitary tumors. Results indicate that 90% of tumors < 2 cm will be completely ablated using the percutaneous approach. However, when tumor size exceeds 3 cm and/or the number of nodules is greater than 3, the rate of treatment success is significantly reduced. In patients with large/multifocal disease, the sole option that has been shown to provide treatment efficacy with moderate improvement in survival is chemoembolization. New therapeutic agents should target biological mechanisms in a tailored strategy, and the demonstration of beneficial results for patients should be obtained by large, randomized, controlled trials comparing active intervention versus no treatment.
The aim of this study was to investigate the usefulness of contrast-enhanced harmonic power Doppler ultrasound (US) for the detection of residual viable hepatocellular carcinoma (HCC) after treatment with transcatheter arterial chemoembolization (TACE). Forty-seven patients with 68 HCC lesions 1.8-9.5 cm in diameter (mean +/- SD 4.3 +/- 1.7 cm) underwent contrast-enhanced power Doppler US, in the harmonic mode, before and after treatment with TACE. Unenhanced spiral CT and contrast-enhanced dynamic MR imaging were also performed to help establish the outcome of therapy. Before treatment, intratumoral blood flow signals were detected at contrast-enhanced harmonic power Doppler US in 65 (95%) of 68 lesions. After TACE, flow signals were no longer detectable in 22 of these 65 lesions, which showed complete response at spiral CT and dynamic MR imaging. In 38 (88%) of the 43 lesions with partial response, intratumoral flow signals were still identified at contrast-enhanced harmonic power Doppler US. Twenty-eight of these 38 lesions underwent additional treatment with percutaneous ethanol injection (PEI) using contrast-enhanced harmonic power Doppler US guidance. Complete response was seen after PEI in 23 of 28 lesions. Contrast-enhanced harmonic power Doppler US proved useful for assessing the therapeutic effect of TACE on HCC and for guiding additional treatment with PEI in cases of partial response.
OBJECTIVE: This study evaluated the currently available treatment modalities for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: One of the most common tumors worldwide, HCC has several known risk factors. Untreated HCC typically has a dismal prognosis. Early detection remains the key to successful treatment of this malignancy. Surgical resection has been the mainstay of treatment for HCC, but newer modalities have been recently introduced. METHODS: The authors evaluated the treatment modalities for HCC. RESULTS: Surgical resection affords 5-year survival rates as high as 45% with more favorable subgroups having 1) small tumors, 2) well-differentiated tumors, 3) unifocal tumors, 4) lack of vascular invasion, 5) absence of cirrhosis, and 6) the fibrolamellar variant (FL-HCC). Resection has been limited primarily by low resectability rates and recurrent disease. Newer therapeutic modalities that appear the most promising are transarterial chemoembolization and percutaneous ethanol injection. Neither therapy has been evaluated in a prospective randomized manner. Combination chemotherapy and surgical intervention may provide the best results, but randomized controlled trials with long-term follow-up are needed. As single-treatment modalities, radiation therapy, intravenous chemotherapy, intra-arterial chemotherapy, and immunotherapy play limited palliative roles. CONCLUSIONS: Surgical resection in the form of partial or total hepatectomy is the preferred treatment for HCC. The early detection of tumors by screening high-risk populations is crucial. Randomized trials of combinations of chemotherapy and surgical resection are needed to demonstrate their potential utility for treatment.
Metastatic involvement of the liver determines the treatment. Hepatic artery chemoembolization (TACE) represents a safe palliative treatment for patients with unresectable liver metastases. Technical treatment, indication and results of the TACE are reported. The results of TACE depend on primary cancer, size and vascularisation of the hepatic tumors. Our results with out patient treatment of 245 patients prove that TACE results in a extremely low rate of side effects. Combination of TACE with local ablative treatment may present potentially curative treatment option for unresectable tumors.