[On the toxicity of the insecticide HCC as an oxyuricide].
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A suspension of iodized oil and anticancer agent was injected into the portal veins of 20 rats with hepatic carcinoma. Oil drops were seen in tumor cell lines, small blood vessels inside the cancer nest, the sinusoid, and the central veins. After injection of oil suspension through the portal vein the distal small vessels were embolized and necrotic changes of tumor cells and their subordinate normal liver cells were observed. The results obtained in this experiment provided a good anatomical and pathological basis for treating liver cancers with the portal vein embolization with chemotherapeutic agents.
To reverse multidrug resistance(MDR) of HepG2 by anti-MDR1 hammerhead ribozyme, an anti-MDR1 hammerhead ribozyme was developed and delivered to P-gp-overproducing human hepatocarcinoma cell line HepG2 by a retroviral vector containing RNA polymerase III promoter. The expression of mdr1/Pgp and Rz was detected in HepG2, HepG2 multidrug-resistant cell line and HepG2 Rz-transfected cells by semi-quantitative RT-PCR and Western blot methods. Moreover, MTT assay was employed to detect the sensitivity of these ribozyme-transfected cells, and Rhodamine123 (Rh123) was used to test the function of Pgp. The Rz- transfected HepG2 cells became doxorubicin-sensitive, which was concomitant with the decreased MDR1 expression. The study showed that the retrovirus vector encoding the anti-MDR1 ribozyme may be applicable to the treatment of MDR cells.
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Liver catalase activity, one of the free-radical scavenger enzymes, has been measured in 22 normal subjects and compared with that of 13 patients suffering from hepatocellular carcinoma. The activity was estimated both in tumor tissue and in tumor-free tissue. A significant reduction of catalase activity was noted in tumor tissue (p less than 0.001) as well as in the adjacent tumor-free tissue (p less than 0.02). In patients with hepatoma, the serum iron level was lower than in normal (p less than 0.01) and was correlated with enzyme activity (r = 0.958). These findings suggest that in hepatocarcinoma the free radical scavenger system is impaired.
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BACKGROUND/AIMS: This retrospective study was undertaken to obtain information relevant to the therapeutic strategy in single hepatocellular carcinoma associated with Child's A and B cirrhosis. METHODS: From a total of 1108 consecutive patients with hepatocellular carcinoma, 391 patients with single, small (< or = 5 cm) hepatocellular carcinoma (260 in Child A class and 131 in Child B class) were observed: 120 were treated by surgical resection, 155 by percutaneous ethanol injection and 116 were untreated. The end point of the study was 3-year survival. The log rank test was used to compare survival among the different groups. RESULTS: In the Child A group the cumulative 3-year survival was 79% for surgery, 71% for percutaneous ethanol injection and 26% for no treatment (p < 0.001 for surgery versus no treatment, p < 0.001 for percutaneous ethanol injection vs no treatment). In patients comparable to the surgical group, i.e. potentially operable, survival was 80% for percutaneous ethanol injection and 30% for no treatment. In the Child B group the 3-year survival was 40% for surgery, 41% for percutaneous ethanol injection and 13% for no treatment (p < 0.01 for surgery vs no treatment and p < 0.001 for percutaneous ethanol injection vs no treatment). CONCLUSIONS: Surgery and percutaneous ethanol injection improve survival in single hepatocellular carcinoma associated with Child A and B cirrhosis compared to untreated patients in the same Child class. A controlled study to identify factors affecting the choice of treatment is justified.
Using quantitative fluorescence in situ hybridization (Q-FISH), the average telomere length of hepatoma cells was assessed by the average telomeric signal intensity of cancer cells relative to that of stromal cells. We demonstrated first the applicability of Q-FISH for tissue sections by comparing Q-FISH and Southern blotting results. Tumors less than 50mm in diameter and with a relative telomeric intensity of less than 0.6 were categorized as group A and the remainder as group B. In group A, the telomere length correlated negatively with tumor size, whereas in group B there was no correlation. Compared with the group A tumors, the group B tumors were of significantly more advanced stage, showed higher telomerase and proliferative activities, and exhibited less differentiated histology. Therefore, we considered that a lack of correlation between telomere length and tumor size, namely, size-independence of telomere length, is associated with unfavorable clinicopathological features of hepatocellular carcinomas.
BACKGROUND: : Effects of radiofrequency ablation (RFA) on hepatic reserve capacity have not been evaluated thoroughly thus far. The aim of our study is to evaluate the factors that influence to hepatic reserve capacity and local recurrence after RFA. PATIENTS AND METHODS: : We studied a total of 243 patients (310 nodules). The study parameters included rates of local recurrence after undergoing RFA as well as factors for delaying recovery of post-RFA albumin levels (age, gender, the presence and absence of anti-HCV antibody, platelet count, GPT level, prothrombin time (PT), Child-Pugh grade, pre-RFA albumin level, alpha-fetoprotein (AFP) level, the number of nodules, tumor size in diameter, hepatic blood control and the coagulation volume after undergoing RFA. RESULTS: : Rates of local recurrence were 6.5%, 10.4% and 12.0% at 1, 2 and 3 years after undergoing RFA, respectively. In the hepatic reserve capacity studies, it took 1.9 and 5.8 months for 50% and 80% of cases, respectively, to restore serum albumin levels to pre-treatment levels after undergoing RFA. There were significant differences in the time of delay in restoration of serum albumin levels with regard to two factors: patients' age >/=60 years (p=0.0351) and tumor size over 3.5cm in diameter (p<0.001). CONCLUSION: : We cosidered that RFA is a safe and efficacious modality, but thorough attention was necessary for such patients with tumor size over 3.5cm in diameter before undergoing RFA, especially in elderly patients.
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Hepatocellular carcinoma is a highly vascular neoplasm usually arising from a cirrhotic liver. Delayed, noncontrast, computed tomography (CT) imaging after 7 to 14 days reveals an oil-based contrast agent to be concentrated in the tumor but not in normal hepatic parenchyma. The aim of this study was to retrospectively correlate the post Lipiodol CT scan findings with respect to tumor size in the explanted liver. We retrospectively reviewed adult patients who had undergone orthotopic liver transplantation between November 1995 and December 2004 and also had an hepatic arteriogram with Lipiodol injection as part of their pretransplant workup. We calculated sensitivity, specificity, false-negativity, false-positivity, and accuracy of the test, as well as positive and negative predictive values. Lipiodol CT exam had sensitivity of 1.0; specificity of 0.6 with a calculated positive predictive value of 0.89 and a negative predictive value of 1.0. Overall accuracy of Lipiodol CT scan test was found to be 0.91, which was superior to an intravenous contrast CT alone. In conclusion, because of the higher sensitivity and accuracy values, hepatic arterial Lipiodol injection can be considered during the pretransplantation workup of high-risk cirrhotic patients, since the current model for End-stage Liver Disease scoring system for hepatocellular carcinoma is built on the ultimate bulk of the tumor. Further multicenter, controlled, large-volume prospective studies are warranted to verify this observation.
Resistance to lenvatinib remains an important limitation in hepatocellular carcinoma treatment. Six patient-derived organoid lines were established and classified as sensitive or resistant according to ex vivo drug responses, retaining histological and immunophenotypic features of matched parental tumors. Resistant organoids showed unchanged ATP activity, whereas sensitive ones exhibited pronounced morphological changes and reduced ATP activity at higher concentrations. Transcriptome sequencing identified 408 upregulated and 269 downregulated genes in resistant versus sensitive organoids, with HIF-1 signaling among altered pathways. In resistant organoids, lenvatinib increased HIF-1α, ANGPT2, and HK3 mRNA, whereas comparable changes were not detected in sensitive organoids. KC7F2 reduced these transcripts and further decreased ATP activity when combined with lenvatinib. In organoid-derived xenografts, this combination suppressed tumor growth and HIF-1 target expression more than lenvatinib alone, indicating HIF-1 signaling contributes to the resistant phenotype and its inhibition may enhance response.
Improvement in our current knowledge of epidemiology, natural history and treatment modalities form the background to generalize the use of ultrasound screening in cirrhosis. The cumulative probability of developing cancer is extremely high in cirrhotics and allows to focus screening programs on a well defined risk group thus maximizing cost-effectiveness. This review article highlights scientific evidences in favour of a generalized practice of US screening.
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