pirarubicin and Carcinoma--Hepatocellular

Cerebral lipiodol embolism (CLE) is an extremely rare complication of transcatheter arterial chemoembolization for hepatocellular carcinoma (HCC). The authors present a case of CLE that occurred after the second hepatic arterial chemoembolization for HCC, and attempt to introduce several plausible mechanisms of CLE, after reporting the clinical and radiological findings and reviewing the medical literature.

Topics: Adult; Antineoplastic Agents; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Contrast Media; Dose-Response Relationship, Drug; Doxorubicin; Humans; Intracranial Embolism; Iodized Oil; Liver Neoplasms; Magnetic Resonance Imaging; Male

To explore the efficiency of single application of lobaplatin in tran-scatheter arterial chemoembolization (TACE) for patients with a primary hepatic carcinoma who were unable or unwilling to undergo surgery.. 173 patients with primary hepatic carcinoma diagnosed by imaging or pathology were randomly divided into experimental and control groups and respectively treated with lobaplatin and pirarubicin hydrochloride as chemotherapeutic drugs for TACE. The amount of iodipin was regulated according to the tumor number and size, and then gelatin sponge or polyvinyl alcohol particles were applied for embolisms. The efficiency of treatment in the two groups was compared with reference to survival time and therapeutic response.. The experimental group (single lobaplatin as chemotherapy drug) was superior to control group (single pirarubicin hydrochloride as chemotherapy drug) in the aspects of survival time and therapeutic response, with statistical significance.. Single lobaplatin can be as a chemotherapy drug in TACE and has better efficiency in the aspects of mean survival time and therapeutic response, deserving to be popularized in the clinic.

Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Case-Control Studies; Chemoembolization, Therapeutic; Cyclobutanes; Doxorubicin; Female; Follow-Up Studies; Hepatic Artery; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Prognosis; Survival Rate

There is no consensus about the most effective method for transarterial chemoembolisation of hepatocellular carcinoma.. The aim of this phase II trial was to compare the efficacy and toxicity of lipiodol transarterial chemoembolisation with amiodarone in association with pirarubicin or doxorubicin versus lipiodol transarterial chemoembolisation with anthracycline alone in a control group.. Patients with unresectable hepatocellular carcinoma and Child-Pugh A/B7 were considered eligible for the trial. transarterial chemoembolisation was repeated every 6 weeks for a maximum of 4 sessions.. Thirteen patients were randomised in the amiodarone group, and 14 were randomised in the control group. The two groups were comparable with respect to their baseline characteristics. The objective response rate according to the EASL criteria was 62% (95% CI 35-88) in the amiodarone group and 50% (95% CI 24-76) in the control group. At 1 and 2 years, survival rates were 77% (95% CI 44-92) and 52% (95% CI 22-75) in the amiodarone group, and 57% (95% CI 28-78) and 40% (95% CI 15-65) in the control group, respectively. There was no difference between the two groups in terms of toxicity.. The results of this study suggest that lipiodol transarterial chemoembolisation with anthracycline and amiodarone was safe but did not increase survival compared with lipiodol transarterial chemoembolisation with anthracycline alone in patients with hepatocellular carcinoma.

Topics: Adult; Aged; Amiodarone; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Disease-Free Survival; Doxorubicin; Ethiodized Oil; Excipients; Female; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Male; Middle Aged; Treatment Outcome

To observe the efficacy and side effects of transarterial chemoembolization (TACE) combined with sorafenib for advanced hepatocellular carcinoma (HCC).. Forty patients with HCC were treated with sorafenib (400 mg bid) after TACE. The efficacy was evaluated according to RECIST 1.1 criteria, and side effects were assessed by NCI CTC 3.0 criteria.. Among the forty cases, one case achieved complete remission (CR), seven cases achieved partial remission (PR), nineteen cases achieved stable disease (SD) and thirteen cases had progressive disease (PD). The disease control rate (DCR) was 67.5%. The overall survival time was 1 - 18 months, and 1-year survival rate was 54.0%. The major adverse events were hand-foot skin reaction, diarrhea and thrombocytopenia.. The combined therapy of TACE and sorafenib is effective and well tolerated for advanced HCC.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Benzenesulfonates; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Combined Modality Therapy; Diarrhea; Disease Progression; Doxorubicin; Female; Follow-Up Studies; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Niacinamide; Organoplatinum Compounds; Oxaliplatin; Phenylurea Compounds; Pyridines; Remission Induction; Sorafenib; Survival Rate; Thrombocytopenia; Young Adult

Long-term results of intra-arterial chemotherapy using a reservoir (IA) for patients with unresectable hepatocellular carcinoma (HCC) were investigated. Ninety-nine patients with unresectable HCC who were treated in our department during the past 7 years were enrolled in this study. Thirty-four out of the 99 patients were treated by IA with a conventional reservoir (SR group), and 21 by IA with a double-lumen reservoir (DR group) by which IA with occlusion of hepatic arterial flow would be possible. The other 44 patients were treated by transcatheter arterial embolization (TAE group). Cumulative 1-and 2-year survival rates were 54.2 and 21.7% in DR group, respectively, and 50.8 and 35.2% in TAE group, respectively. The results of these two groups were statistically equivalent, and were more favorable than those of the SR group. Cumulative patency rate of reservoirs was maintained at 93.7% after one year and at 61.8% after two years. No difference was recognized in this rate according to the type of reservoir. We concluded that IA with a double-lumen reservoir should be taken into consideration as one of the strategies for treatment of unresectable HCC. However, maintenance of catheter-patency would be necessary for satisfactory outcome.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Cisplatin; Doxorubicin; Embolization, Therapeutic; Epirubicin; Female; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Liver Neoplasms; Male; Middle Aged; Survival Rate

Twenty patients with unresectable hepatocellular carcinoma were treated by intra-arterial subsegmental injection of Cisplatin/4-0-Tetrahydro-Pyranyl-adriamycin Lipiodol suspension (CTLS). The mean single doses of Lipiodol, cisplatin and THP were 2.3 ml, 85 mg and 8.9 mg, respectively. The therapy was given once in 10 patients, twice in 8 and 3 times in two. Over 25% reduction in tumor size was recognized in 12 patients (60%). Fifty or more % decrease of alfa-feto-protein (AFP) was observed in all of 7 patients (100%) with the initial serum AFP level of more than 200 ng/ml. Although transitional and mild symptoms, such as fever, abdominal pain and vomiting were recognized in some cases, no severe complications were encountered. This method is promising as an excellent procedure for unresectable hepatocellular carcinoma.

Topics: Aged; alpha-Fetoproteins; Antibiotics, Antineoplastic; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cisplatin; Doxorubicin; Female; Humans; Injections, Intra-Arterial; Iodized Oil; Liver Neoplasms; Male; Middle Aged; Suspensions

A clinical trial of transarterial chemoembolization for hepatocellular carcinoma using pirarubicin (4'-0-tetrahydropyranyladriamycin, THP) was performed. Although adriamycin has been widely utilized for chemoembolization on the hepatocellular carcinoma, myocardial toxicity has been occasionally observed as its serious side effect. THP has an advantage that myocardial and gastrointestinal complications are less frequent than adriamycin. Ten patients with hepatocellular carcinoma were included in this study. Emulsion of 30-60 mg of THP and lipiodol was administered through a catheter inserted into the right or left hepatic artery, and thereafter, transarterial embolization was performed. PR was observed in seven of the ten patients and MR in two. Only one patient showed NC. Serum alpha-fetoprotein levels decreased in nine of the ten patients, and PIVKA II in the peripheral blood disappeared in all five patients that had been positive before the chemo-embolization four weeks after the treatment. Side effects included nausea in two patients just after administration of THP, but leukopenia below 2,000/cmm, was not observed in any of the patients. No other serious side effect was observed. From these results, THP was suggested to be a useful chemotherapeutic agent for hepatocellular carcinoma.

Topics: Aged; alpha-Fetoproteins; Biomarkers; Carcinoma, Hepatocellular; Clinical Trials as Topic; Doxorubicin; Embolization, Therapeutic; Female; Hepatic Artery; Humans; Iodized Oil; Liver Neoplasms; Male; Middle Aged; Protein Precursors; Prothrombin

Chemoresistance has become a primary hurdle in the therapeutic outcome of hepatocellular carcinoma. Substantial evidences have demonstrated that microRNAs (miRNAs) are closely associated with the chemoresistance of hepatocellular carcinoma (HCC). Our investigation is aimed at testifying the influence of microRNA-15a-5p (miR-15a-5p)/eukaryotic translation initiation factor 4E (eIF4E) on hepatocellular carcinoma resistance to pirarubicin (THP). In our study, miR-15a-5p expression was increased in THP-treated HepG2 cells. Downregulation of miR-15a-5p blocked cell growth and elevated cell apoptosis of HepG2 cells treated with THP. Moreover, eIF4E was verified as a direct target of miR-15a-5p by binding its 3'-UTR, which was confirmed by luciferase report experiment. Additionally, eIF4E was negatively associated with the miR-15a-5p expression in HepG2 cells. Mechanically, eIF4E was proven as a specific downstream of miR-15a-5p and mediated the effects of miR-15a-5p on cell viability and apoptosis of HepG2 cells treated with THP. These findings supported that miR-15a-5p facilitated THP resistance of hepatocellular carcinoma cells by modulating eIF4E, thus providing an experimental basis that miR-15a-5p might act as a novel diagnostic target in hepatocellular carcinoma resistance to THP.

Topics: 3' Untranslated Regions; Antineoplastic Agents; Apoptosis; Binding Sites; Carcinoma, Hepatocellular; Cell Proliferation; Computational Biology; Doxorubicin; Drug Resistance, Neoplasm; Eukaryotic Initiation Factor-4E; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Humans; Liver Neoplasms; MicroRNAs

To retrospectively analyze the safety and long-term clinical efficacy of gelatin sponge microparticles combined with the chemotherapy drug pirarubicin for hepatic transcatheter arterial chemoembolization (GSMs-TACE) in order to treat breast cancer liver metastasis (BCLM).. Twenty-seven BCLM patients who underwent GSMs-TACE from July 2010 to July 2016 were enrolled. Tumor target blood vessels were slowly and regionally embolized with absorbable gelatin sponge particles and pirarubicin injections. Plain computed tomography (CT) scans and biochemical indexes were re-examined at 4 days after treatment, and enhanced CT scans or magnetic resonance images and biochemical indexes, 1 month later. For patients with stable tumors, the follow-up period was 2 to 3 months, and the tumor response was evaluated using Modified Response Evaluation Criteria in Solid Tumors. Adverse reactions, survival time, and prognostic factors were assessed.. By October 2019, 27 patients with BCLM had undergone GSMs-TACE, with an average of 2.44 ± 1.58 treatments. The 1-, 3-, and 5-year survival rates were 62.96%, 22.22%, and 14.81%, respectively, and the mOS was 22.0 months. No serious complications, such as acute liver failure and liver abscess, had occurred. There were two cases of acute cholecystitis that recovered after symptomatic treatment. Multivariate analysis of the prognosis showed that the primary tumor size, number of metastatic lymph nodes, estrogen receptor/progesterone receptor (ER/PR) status, and time to postoperative liver metastasis and combination therapy were statistically significant.. The overall prognosis of BCLM was poor. GSMs-TACE was safe and effective for BCLM treatment and could prolong the median survival time of patients. Therefore, it is worthy of widespread clinical application.

Topics: Breast Neoplasms; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Doxorubicin; Female; Gelatin; Humans; Liver Neoplasms; Prognosis; Retrospective Studies

This study aimed to investigate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) treatment in Barcelona Clinic Liver Cancer (BCLC) stage C liver cancer patients. In 39 patients with BCLC stage C liver cancer, after the first cycle of DEB-TACE, 2 (5.1%) and 24 (61.5%) patients achieved complete response (CR) and partial response (PR) to give an overall objective response rate (ORR) of 66.7%. With respect to the second cycle of therapy, the ORR was higher in patients receiving DEB-TACE compared with those receiving cTACE (57.1% vs. 11.1%). After the first cycle of DEB-TACE treatment, the percentages of abnormal albumin (ALB), total protein (TP), total bilirubin (TBIL), and alanine aminotransferase (ALT) worsened at 1 week and recovered at 1 month. The number of patients with abnormal aspartate aminotransferase (AST) did not increase at 1 week but elevated at 1 month. After the second cycle of DEB-TACE or cTACE treatment, no difference was observed between cTACE and DEB-TACE in terms of all adverse events (AEs) at all visits, and most of the AEs did not change after the second cycle in both groups. The most common AEs after the first and second treatment cycles were pain, fever, and nausea/vomiting. These results demonstrate that DEB-TACE offers patients with BCLC stage C liver cancer a clinically active short-term treatment that is safe and relatively well tolerated.

Topics: Adult; Aged; Alanine Transaminase; Antineoplastic Agents; Aspartate Aminotransferases; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Doxorubicin; Drug Delivery Systems; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Liver Neoplasms; Male; Microspheres; Middle Aged; Neoplasm Staging; Treatment Outcome

Pirarubicin (THP) is a new generation cell cycle nonspecific anthracycline anticancer drug. Pirarubicin and pirarubicin-based combination therapies have been demonstrated to be effective against HCC in TACE. However, the drug resistance limits its therapeutic efficacy. Receptor-interacting protein kinase 1 (RIPK1) displays a critical role in cell death. Here we found that RIPK1 and p21 may participate in the resistance to pirarubicin. In this study, we first found that inhibition of RIPK1 significantly decreased pAKT and increased p21, accompanied by G0/G1 phase cell cycle arrest and cell anti-proliferation in pirarubicin-treated hepatocellular carcinoma cells. Moreover, phosphorylation of AKT reversed the anti-proliferative effect of RIPK1 inhibitor in HCC, which proved that RIPK1-AKT-P21-dependent pathway played a key role in pirarubicin resistance. Using a mouse xenograft model, we further found that RIPK1 inhibitor combined with pirarubicin exerted synergistic anti-tumor effect

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Cell Line, Tumor; Chemoembolization, Therapeutic; Cyclin-Dependent Kinase Inhibitor p21; Doxorubicin; Drug Resistance, Neoplasm; Humans; Imidazoles; Indoles; Liver Neoplasms; Male; Mice; Mice, Nude; Phosphorylation; Proto-Oncogene Proteins c-akt; Receptor-Interacting Protein Serine-Threonine Kinases; RNA, Small Interfering; Xenograft Model Antitumor Assays

Topics: Abdominal Injuries; Accidents, Traffic; Aged; Antineoplastic Agents; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Contrast Media; Doxorubicin; Ethiodized Oil; Humans; Intracranial Embolism; Liver Neoplasms; Male

MicroRNAs function as oncomiRs and tumor suppressors in diverse cancers. However, the utility of specific microRNAs in predicting the clinical benefit of chemotherapy has not been well-established. Here, we investigated the correlation between microRNA-21 expression and hepatic arterial infusion chemotherapy with 5-fluorouracil and pirarubicin (HAIC) for hepatocellular carcinoma (HCC). We found that HCC patients with low microRNA-21 levels in tumors tended to have a longer time to recurrence and disease-free survival. We demonstrated that microRNA-21 suppression in combination with 5-fluorouracil and pirarubicin treatment inhibited tumor growth in subcutaneous xenograft mice models. Mechanistically, the AP-1 and microRNA-21-mediated axis was verified to be a therapeutic target of cytotoxic drugs and deregulation of this axis led to an enhanced cell growth in HCC. Taken together, our findings demonstrate that microRNA-21 is a chemotherapy responsive microRNA and can serve as a prognostic biomarker for HCC patients undergoing HAIC. Targeting microRNA-21 enhances the effect of chemotherapeutic drugs, thereby suggesting that microRNA-21 suppression in combination with HAIC may be a novel approach for HCC treatment.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Blotting, Western; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Disease-Free Survival; Doxorubicin; Female; Fluorouracil; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Immunosuppressive Agents; Liver Neoplasms; Male; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; Middle Aged; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factor AP-1; Tumor Burden; Xenograft Model Antitumor Assays

Golgi protein 73 (GP73) is a promising biomarker of hepatocellular carcinoma (HCC). It decreases after surgical resection, and resumes upon recurrence, indicating a potential indicator for the effectiveness of the treatment. But changes of GP73 after transcatheter arterial chemoembolization (TACE) have not been reported so far. This study was to investigate the dynamic changes of GP73 in HCC patients after TACE treatment, and the possible underlying mechanisms in the cell cultures.. Blood samples were collected from 72 HCC patients, before TACE, at day 1 and day 30 after TACE. GP73 levels were measured by Western blotting. The dynamic changes of GP73 were analyzed and compared with image changes and clinical data. The effects of chemotherapeutic agents (5-FU and pirarubicin) on GP73 expression were tested in three HCC cell lines (HepG2, HCCLM3 and MHCC97H).. The GP73 level was significantly elevated at day 1 and day 30 after TACE in HCC patients compared with that before the procedure (P<0.05). There was no statistical difference between the two time points after TACE, nor correlation between GP73 levels and clinicopathological features, tumor metastasis, and patient survival. Pirarubicin, not 5-FU, significantly increased GP73 expression in three cell lines.. Unlike surgical resection which decreases the GP73 level, TACE significantly increased GP73 expression in patients with HCC. No correlations were observed among GP73 levels, tumor characteristics and prognosis of patients with HCC.

Topics: Adult; Aged; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Disease Progression; Disease-Free Survival; Doxorubicin; Female; Fluorouracil; Hep G2 Cells; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Male; Membrane Proteins; Middle Aged; Prospective Studies; Time Factors; Treatment Outcome; Up-Regulation

To assess the effect and safety of lobaplatin combinated floxuridine /pirarubicin in transcatheter hepatic arterial chemoembolization(TACE) of unresectable primary liver cancer.. TACE combined with the chemotherapy regimen was used to treat 34 unresectable primary liver cancer patients. DSA/ MRI/CT/blood routine examinations were used to evaluate short term activity and toxicity after 4-5 weeks, the process being repeated if necessary.. Among the 34 cases, 1 (2.9%) showed a complete response, 21 (61.7%) a partial response, 8 (23.5%) stable disease, and 4 progressive disease, with a total effective rate of 67.6%. The content of alpha fetoprotein dropped by over 50% in 20 cases (58.8%). The rate of recovery was hepatalgia (88.2%), ascites (47.1%), appetite (55.9%), Performance Status(30.4%). The median follow-up time (MFT) was 281 days (63-558 days), and median progression-free survival was 118.5 days (95%, CI:88.8-148.2 days). Adverse reactions (III-IV grade) were not common, with only 4 cases of vomiting and 2 cases of thrombocytopenia (III grade).. Lobaplatin-based TACE is an effective and safe treatment for primary liver cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cyclobutanes; Disease-Free Survival; Doxorubicin; Female; Floxuridine; Hepatic Artery; Humans; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds

Topics: Adult; Angiography, Digital Subtraction; Antineoplastic Agents; Carcinoma, Hepatocellular; Collateral Circulation; Doxorubicin; Embolization, Therapeutic; Ethiodized Oil; Humans; Liver Neoplasms; Male; Mitomycin; Skin; Skin Ulcer; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Wound Healing

Hepatocellular carcinoma (HCC) in children is rare, and the prognosis has been poor because of its advanced stage at diagnosis and unresponsiveness to chemotherapy. We report a 13-year-old boy with ruptured HCC in the left trisegment. When hemostasis of the ruptured surface was achieved in the emergency operation, the left branch of the portal vein and the left hepatic artery were ligated at the same time. The volume of the future liver remnant (FLR), that is, his right posterior sector, increased from 56% on admission to 70% of his standard liver volume on day 2. Blood level of serum protein induced by vitamin K absence or antagonist ІІ started to decrease immediately. Left trisegmentectomy was successfully performed 10 days later, followed by chemotherapy. He has been well with a 2-year survival without recurrence. When the FLR is considered relatively small for a major hepatic resection, the selective ligation of the portal vein and the hepatic artery, which feed HCC, seems to be beneficial. This is because it may induce enlargement of the FLR, increasing the safety of the hepatectomy as preoperative portal vein embolization does before a major hepatectomy in adult patients with HCC, and the latter suppresses the tumor while waiting for the planned hepatectomy.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Basketball; Carcinoma, Hepatocellular; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Doxorubicin; Hemoperitoneum; Hemostasis, Surgical; Hepatectomy; Hepatic Artery; Humans; Ligation; Liver; Liver Neoplasms; Liver Regeneration; Male; Organ Size; Portal Vein; Radiography; Rupture; Shock; Vascular Surgical Procedures

Further to a previous study whereby we reported that an in vitro emulsion of pirarubicin, amiodarone, and lipiodol was more stable and cytotoxic than a classic doxorubicin-lipiodol mixture, we designed a pilot study to evaluate efficacy and toxicity of a transarterial chemoembolization (TACE) procedure using a combination of pirarubicin, amiodarone, lipiodol, and gelatin sponge.. The 43 patients included in this study underwent TACE for unresectable hepatocellular carcinoma. Computed tomography scans were performed to assess tumor response (RECIST) and lipiodol uptake after the first session. Median follow-up lasted 30 months. Endpoints were overall and progression-free survival. Survival was estimated using Kaplan Meier estimations and compared using log-rank tests. Univariate and multivariate Cox analyses were used to calculate hazard ratios with their 95% confidence interval (CI).. Twenty-seven (67.5%) patients had alcoholic cirrhosis. Mean tumor size was 9.5 cm (1-20 cm) and 37/43 were multifocal or diffuse. Cancer of the liver Italian program score was 0 in 7/40 and 1 in 16/40. Mean number of TACE sessions was 3.5 (1-11). There were 3 treatment-related deaths (2 severe sepsis, 1 bowel perforation). A partial response and a stable disease were observed in 12 (28%) and 29 (67%) patients, respectively. Median overall and progression-free survivals were 29 months (95% CI: 13.8-45) and 15 months (95% CI: 11.5-20.8), respectively. Cancer of the liver Italian program score 25% (P = 0.003) were independent prognostic factors for better overall survival.. This new TACE procedure is safe with a high overall survival rate and certainly deserves phase III investigation to compare it with classic treatments such as doxorubicin-lipiodol TACE.

Topics: Aged; Aged, 80 and over; Amiodarone; Antineoplastic Agents; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Doxorubicin; Female; Humans; Immunosuppressive Agents; Iodized Oil; Liver Neoplasms; Male; Middle Aged; Pilot Projects; Prognosis; Survival Rate; Tomography, X-Ray Computed; Treatment Outcome

Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Contrast Media; Diagnosis, Differential; Doxorubicin; Hepatectomy; Humans; Liver Neoplasms; Male; Middle Aged; Myasthenia Gravis; Paraneoplastic Syndromes, Nervous System; Treatment Outcome

Hepatocellular carcinoma arises from hepatocytes, it is the most common primary malignant tumor of the liver and accounts for the majority of liver cancers. Pirarubicin is a compound analog to the antineoplastic anthracycline antibiotic doxorubicin. Thereby as an intercalator of DNA, pirarubicin has shown efficacy in reducing tumor activity of hepatocellular carcinoma. Utilizing in silico optimized similarity of structure search of data base and replacement by isosteres, a total of nine analogs to pirarubicin were generated. The molecular size of ring substituents (approximately a base pair) were preserved and isosteres chosen to preserve the weak electrostatic properties permitting DNA intercalation. Only a small range in molecular weight and volume was permitted in order to preserve intercalation activity. Standard deviations for polar surface area, number of heavy atoms, molecular weight, molecular volume, and number of oxygens and nitrogens, were only 3.98%, 1.76%, 16.5%, 2.51%, and 0%, respectively, of the overall average for these properties. Variation of the target substituent resulted in insignificant changes in many properties; there was a striking variation in the lipophilic property Log P. Values of Log P ranged from 0.142 to 2.078 inclusive of pirarubicin and plays an important role in bioavailability. Hierarchical cluster analysis indicated that all analogs, except analog 6, were substantially similar to pirarubicin. A similar outcome was obtained from non-metric multidimensional scaling of descriptors. However detrended correspondence analysis distinguished both analogs 6 and 5 from the remaining analogs and pirarubicin. Nonhierarchical K-means clustering analysis determined greater differentiation among the analogs and pirarubicin. Analysis of similarity (ANOSIM) affirmed all compounds to be highly similar which shows structural optimization was achieved.

Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Cluster Analysis; Databases as Topic; DNA; Doxorubicin; Drug Discovery; Humans; Liver Neoplasms; Models, Chemical; Molecular Weight; Multivariate Analysis; Nitrogen Compounds; Oxygen Compounds; Pattern Recognition, Automated; Static Electricity

To investigate the value of in vivo proton magnetic resonance spectroscopy (MRS) in the assessment of hepatocellular carcinoma (HCC) and monitor its metabolic change shortly after transcatheter arterial chemoembolization (TACE).. In this prospective study, 28 consecutive patients with large HCC (> or = 3 cm in diameter) confirmed by fine needle aspiration biopsy were recruited. The 1H MRS of all hepatic lesions and some uninvolved liver parenchyma were performed with 1. 5T whole body MR scanner. Among them, 15 cases were evaluated again about one week after TACE. The main metabolites such as choline and lipid before and after interventional therapy were measured to assess the early response of the tumor.. The technical success rate of 1H MRS in liver was high (33/41, 80%), closely related to breath motion, location of lesion, and size of voxel. In spectra, the choline compound peak of HCC elevated compared with uninvolved liver parenchyma. After TACE, both the amplitude and the area of choline resonance peak significantly descended (choline-to-lipid ratios from 0.352 +/- 0.080 to 0.167 +/- 0.030, P = 0.026; from 0.205 +/- 0.060 to 0.070 +/-0.020, P = 0.042, respectively); yet lipid resonance peak ascended.. In vivo 1H MRS is technically feasible for the evaluation of large focal hepatic lesions, however, the reproducibility and stability are not as good as routine MR scan. 1H MRS can monitor the early stage metabolic changes of HCC after TACE but limitation like quantification still exists.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cisplatin; Doxorubicin; Female; Humans; Liver; Liver Neoplasms; Magnetic Resonance Spectroscopy; Male; Middle Aged

Although chemoembolization is known to be an effective palliative treatment in hepatocellular carcinoma, it has a limited effect in large tumors. We report the case of a patient with a large hepatocellular carcinoma of the left liver who had a significant and sustained clinical response after six sessions of chemoembolization with a pirarubicin/amiodarone/lipiodol emulsion. Pirarubicin is an anthracycline which penetrates faster than doxorubicin into cancer cells. Amiodarone is a multidrug resistance inhibitor. Polysorbate 80, an excipient of injectable amiodarone stabilizes the anthracycline/lipiodol emulsion. The clinical efficacy of this new formulation could be evaluated in a phase II clinical trial.

Topics: alpha-Fetoproteins; Amiodarone; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Contrast Media; Doxorubicin; Enzyme Inhibitors; Humans; Immunosuppressive Agents; Injections, Intra-Arterial; Iodized Oil; Liver Neoplasms; Male; Middle Aged

A patient with liver metastasis of pancreatic cancer received chemotherapy using mitomycin C and degradable starch microspheres. The patient was a 52-year-old woman who had undergone surgery for cancer of the head of the pancreas in October 1996. She had stage III disease and was followed up as an outpatient on oral therapy with a combined uracil and tegafur preparation. In October 2000, abdominal computed tomography (CT) scans detected multiple liver metastases. Three courses of intra-arterial infusion of mitomycin C and microspheres (1000 mg) resulted in regression of her tumor and a decrease of tumor marker levels. After three more courses of this therapy, the patient developed bile duct necrosis and died of disseminated intravascular coagulation. As her metastases were controlled for about 7 months, hepatic arterial infusion of mitomycin C and degradable starch microspheres appears to be useful for treating liver metastasis of pancreatic cancer, but careful attention should be paid to the risk of severe complications such as bile duct necrosis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bile Duct Diseases; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Chemotherapy, Adjuvant; Combined Modality Therapy; Doxorubicin; Fatal Outcome; Female; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Middle Aged; Mitomycin; Necrosis; Neoplasm Staging; Pancreatic Neoplasms; Pancreaticoduodenectomy; Risk Assessment; Starch; Tomography, X-Ray Computed

There is no well-defined curative treatment for advanced and unresectable hepatocellular carcinoma. The widely used transarterial chemoembolization (TACE) with a doxorubicin-Lipiodol emulsion has not been shown to improve survival in randomized studies. Further, obstruction of the hepatic artery used in the procedure is badly tolerated in patients with cirrhosis. Drugs with a more rapid penetration into the cancer cells are likely to eliminate the need for obstruction of the hepatic artery. We therefore compared the cytotoxicity of another anthracycline pirarubicin with that of the commonly used doxorubicin. In this report, we show that pirarubicin has a greater in vitro cytotoxic effect than doxorubicin on the HepG2 and Hu-H7 human hepatoma cell lines. Pirarubicin emulsion with Lipiodol is more stable at 37 degrees C than doxorubicin-Lipiodol. Moreover, pirarubicin accumulates at a greater extent in the oil phase, permitting Lipiodol to act as a slow-releasing vector for the anthracycline. Further, amiodarone, a multidrug resistance inhibitor, was shown to decrease the intrinsic resistance of HepG2 and Hu-H7 cells to both anthracyclines, and the presence of polysorbate 80 in the amiodarone preparation increased the stability of the anthracycline-Lipiodol emulsions. We therefore conclude that pirarubicin is a better candidate for TACE than doxorubicin. The rapid and increased cytotoxicity of pirarubicin on hepatoma cancer cells and the stability of the pirarubicin-Lipiodol amiodarone emulsion could avoid the complete obstruction of the hepatic artery by Gelfoam sponges, and provide a better tolerated method of TACE in patients with latent liver insufficiency.

Topics: Amiodarone; Antibiotics, Antineoplastic; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Chromatography, High Pressure Liquid; Doxorubicin; Drug Resistance, Multiple; Drug Stability; Emulsions; Enzyme Inhibitors; Humans; Iodized Oil; Liver Neoplasms; Tetrazolium Salts; Thiazoles; Tumor Cells, Cultured

The current study was conducted to evaluate retrospectively the effects of three kinds of regimens used in transcatheter arterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC) and patients' prognosis, and to analyze their prognostic factors.. The study population was comprised of 152 patients who were treated by TACE alone. Three kinds of regimens were used successively: doxorubicin hydrochloride (ADM) and mitomycin C mixed with iodized oil in 26 patients (ADMOS group), a combination of cisplatin (CDDP) solution and ADMOS in 70 patients (CDDP-ADMOS group), and CDDP powder and pirarubicin hydrochloride mixed with iodized oil in 56 patients (CTLS group). The CTLS group was comprised of patients with significantly worse background factors than the other two groups.. The initial tumor response rate with a > 50% reduction was 12%, 23%, and 30%, respectively, in the ADMOS, CDDP-ADMOS, and CTLS groups. CTLS was significantly more effective than ADMOS (P < 0.05), and slightly but not significantly better than CDDP-ADMOS (P <0.1). The cumulative survival rates for the ADMOS, CDDP-ADMOS, and CTLS groups were 59.0%, 70.1%, and 72.0%, respectively, at 1 year; 0%, 16. 3%, and 29.8%, respectively, at 3 years; and 0%, 4.1%, and 16.8%, respectively, at 5 years, with median survival times of 448 days, 574 days, and 758 days, respectively. The CTLS group showed a slightly but not significantly better survival than the ADMOS and CDDP-ADMOS groups (P <0.1). Multivariate analysis indicated that the significantly important prognostic factors (in order) were extrahepatic metastasis followed by the TACE regimen, serum alpha-fetoprotein levels, and portal vein involvement and that CTLS was the best of the three regimens.. Although TACE, using an effective regimen, improves clinical results, tumor factors appear to be more important when determining prognosis.

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antineoplastic Agents; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cisplatin; Disease-Free Survival; Doxorubicin; Drug Combinations; Female; Humans; Infusions, Intra-Arterial; Iodized Oil; Liver Neoplasms; Male; Middle Aged; Mitomycin; Multivariate Analysis; Prognosis; Retrospective Studies; Time Factors

A 46-year-old male with unresectable hepatocellular carcinoma (HCC) comprised of severe liver dysfunction was treated by intra-arterial infusion chemotherapy through an implantable reservoir. During 39 months, a total amount of THP-ADR 420 mg, ADR 70 mg and CDDP 350 mg was infused. Through the therapy, the tumor size on the lateral segment was well controlled, and serum AFP and PIVKA-II levels were also lowered. No severe side effect was observed. The patient was treated on an outpatient basis, and a good quality of life during therapy was maintained. This case suggests that THP-ADR may play an important role in a combined intraarterial chemotherapy for advanced HCC.

Topics: Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Cisplatin; Doxorubicin; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Liver Neoplasms; Male; Middle Aged

Topics: Antibodies; Carcinoma, Hepatocellular; Combined Modality Therapy; Doxorubicin; Epirubicin; Ferritins; Humans; Iodine Radioisotopes; Liver Neoplasms; Radioimmunotherapy; Tumor Cells, Cultured

We studied the effect of adjuvant hepatic arterial chemotherapy with THP-adriamycin (THP) and carboplatin (CBDCA) in patients with hepatocellular carcinoma (HCC). Fifteen patients were treated by intraarterial infusion of THP 30 mg on the second and third week after hepatectomy. CBDCA 450 mg was further injected on the fourth week (group A). Intrahepatic arterial administration of the drug was carried out through the subcutaneously implanted reservoir; one to five courses of the protocol were performed (average 2 times). Transient leukocytopenia occurred in six cases, liver dysfunction in one case, duodenal ulcer in one case and occlusion of the catheter connected reservoir in three cases. Forty-two patients not treated with this protocol postoperatively were employed as historical control (group B). There were no significant differences between group A and B in operative procedures, tumor stage, clinical stage, tumor size and other histopathological findings including nuclear DNA ploidy pattern. The two-year cumulative disease-free survival rate was 78% in group A, which was significantly better than the 55% of group B (p < 0.05). It may be concluded that intrahepatic arterial chemotherapy using THP and CBDCA plays an important role to prevent recurrences of the tumor after hepatectomy in patients with HCC.

Topics: Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Hepatocellular; Doxorubicin; Drug Administration Schedule; Female; Hepatic Artery; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Liver Neoplasms; Male; Middle Aged; Survival Rate

Seventeen patients with hepatocellular carcinoma were treated by intraarterial injection of CTL suspension. The doses of CTL suspension, CDDP and THP(mean +/- SD)/injection were 4.1 +/- 1.6 ml, 81.9 +/- 31.6 mg and 13.5 +/- 5.2 mg, respectively. The therapy was given once in 10 patients, twice in 6 and 4 times in one. Over 50 per cent reduction in tumor size was obtained in 5 patients (30%). Fifty or more % decrease in serum alpha-feto-protein (AFP) levels was observed in 3 of 7 patients (43%) with the initial serum AFP level of more than 200 ng/ml, Fever, abdominal pain, nausea and vomiting were noted in most cases. However, they disappeared within 2 weeks after therapy was completed. No severe complications were encountered except one case of a liver abscess which healed by administration of antibiotics. No severe changes in laboratory data were observed. This study suggests that a new method of intraarterial injection must be developed to enhance the therapeutic effect even more, in addition to an increased injection dose of CDDP/THP-LPD and higher concentration of CDDP and THP in LPD.

Topics: Adult; Aged; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cisplatin; Doxorubicin; Female; Hepatic Artery; Humans; Iodized Oil; Liver Neoplasms; Male; Middle Aged

A 63-year-old Japanese woman who was being treated for liver cirrhosis was diagnosed as having hepatocellular carcinoma in the caudate lobe of the liver. Transcatheter hepatic arterial chemoembolization was performed for this lesion, but severe neutropenia occurred. To restore white blood cell (WBC) counts, recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered (250 micrograms per day during 10 days, intravenously). Subsequently, WBC counts recovered immediately without side effects. This suggests that rhG-CSF could be useful for the treatment of neutropenia after chemoembolization, even in cirrhotic patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Doxorubicin; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Humans; Liver Cirrhosis; Liver Neoplasms; Middle Aged; Neutropenia; Recombinant Proteins

Fourteen cases of malignant liver tumor in childhood were experienced in our department during past 14 years. Since 1984 we have performed preoperative targeting anticancer chemotherapy using oily anticancer agents such as THP-adriamycin 30 mg/m2. These oil emulsion was making with 20 mg amounts of THP-adriamycin dissolved in 5 ml urographin and 15 ml volume of lipiodol. These mixture were administered by catheterizing the hepatic artery under X-ray monitoring in 6 cases with hepatoblastoma. Remarkable anticancer effects of this targeting chemotherapy were achieved, the serum AFP level and tumor size both showing a decrease in all cases, and the resectability of tumor showing a increase in 5 among 6 cases in comparison with 50% resectability before 1983.

Topics: Adolescent; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Contrast Media; Doxorubicin; Drug Carriers; Female; Humans; Infant; Iodized Oil; Liver Neoplasms; Male

Antitumor drugs dispersed in a lipid lymphographic medium (Lipiodol, Laboratorie Guerbert, Rue Jean-Chaptal, France) were intraarterially administered in two infants with unresectable hepatoblastoma. The Lipiodol and antitumor drug complex was found to selectively accumulate in the tumor and was associated with a marked reduction in the tumor size and a 50% decrease in the alpha-fetoprotein (AFP) level after 4 days in one patient and 16 days in the other. The tumor was successfully resected by right trisegmentectomy in one patient, but surgery was not performed on the other because of evidence of pulmonary metastasis. The patients had moderate fever for 2 to 3 days after the intraarterial chemotherapy. It is believed that intraarterial chemotherapy with Lipiodol may be a useful preoperative chemotherapy for initially unresectable hepatoblastoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Cisplatin; Doxorubicin; Drug Carriers; Fluorouracil; Hepatic Artery; Humans; Infant; Injections, Intra-Arterial; Iodized Oil; Liver Neoplasms; Male

Intraarterial injection of anti-tumor drugs (THP-ADR, CDDP, 5-FU) dispersed in lipid contrast medium (Lipiodol, Laboratorie Guerbert, France) was used in an infant with initially unresectable hepatoblastoma. Lipiodol complex selectively accumulated in the tumor tissue and may keep the chemotherapeutic agents in the tumor tissue for a longer period of time, and a significant reduction of the tumor with a four-day half-life of alpha-fetoprotein (AFP) was followed immediately after the institution of chemotherapy. Successful resection of decreased tumor by extended right hepatectomy under more favorable conditions was performed 2 months after diagnosis. Intraarterial chemotherapy with Lipiodol was particularly useful in potentiating the cytoreduction of anti-tumor drugs and was also useful in reducing the toxicities of anti-tumor drugs to the host.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Cisplatin; Doxorubicin; Fluorouracil; Humans; Infant; Injections, Intra-Arterial; Iodized Oil; Liver Neoplasms; Male