Hepatocellular Carcinoma In Regions Research Articles

Transarterial Chemoembolization Combined with Simultaneous Thermal Ablation for Solitary Hepatocellular Carcinomas in Regions with a High Risk of Recurrence.

We evaluated the safety and efficacy of transarterial chemoembolization combined with percutaneous thermal ablation (radiofrequency or microwave ablation) in the treatment of solitary hepatocellular carcinoma tumors ranging from 2 to 4.5 cm at subdiaphragmatic, subcapsular, or perivascular locations. Fifteen patients (12 men, mean [range] age of 66.6 ± 10.88 [34-75] y) who received transarterial chemoembolization combined with simultaneous percutaneous radiofrequency ablation (n = 5) or microwave ablation (n = 10) for hepatocellular carcinoma in regions with high risk of recurrence (subdiaphragmatic, subcapsular, or perivascular) between 2012 and 2018 were evaluated. We retrospectively investigated tumor diameter and localization, success rate, safety, local efficacy (imaging at month 1 after treatment), local tumor response (3 months posttreatment), local tumor progression, intrahepatic distant recurrence, overall survival and complications. Tumor diameter ranged from 20 to 45 mm (mean 31.7 ± 7.37 mm). Hepatocellular carcinoma diameter was 2 to 3 cm in 7 patients and 3.1 to 4.5 cm in 8 patients. The technical success rate was 100%, with no life-threatening complications. At enhanced imaging at 1-month follow-up, the complete necrosis rate was 100%; at 3 months, 100% of patients had a complete response. During a mean follow-up of 26 ± 13.6 months, 7 patients (46.7%) had tumor progression. Three patients (20%) had local tumor response, and 4 patients (26.7 %) experienced distant recurrences in the untreated liver. The mean local tumor progression and mean intrahepatic distance recurrence times were 11 months and 29.5 months, respectively. Overall survival rates were 100% at 1 year, 73% at 3 years, and 47% at 5 years. Transarterial chemoembolization combined with simultaneous percutaneous thermal ablation is safe, feasible, and effective in enhancing the local control rate for solitary hepatocellular carcinoma ranging from 2 to 4.5 cm in regions with high risk of recurrence.

Somatic mutations in human cancer: applications in molecular epidemiology

The tumour suppressor protein p53 mediates cell-cycle arrest, DNA repair and apoptosis after activation by multiple forms of cellular stresses. When activated, this "master protein" modulates its response depending on the type and intensity of the stress. The TP53 gene with its nearly 20,000 described mutations is the most mutated gene in cancer. Most mutations are missense and occur at over 200 codons within the central portion of the gene. In several cancers, the distribution of mutation types and sites follow a specific pattern reflecting the effects of environmental mutagens. An example for such a "mutagen fingerprint" is TP53 mutation at codon 249 in hepatocellular carcinoma in regions of the world characterised by high levels of the mutagen aflatoxin B1 and endemic HBV infection. Recently, TP53 mutations have been detected in surrogate sources of genetic material such as free circulating DNA isolated from plasma. Plasma TP53 mutations can be detected in the blood of pre-cancer and cancer patients, with potential application for early cancer detection. Thus, TP53 mutations have multiple applications as markers of mutagenic exposures, or as intermediate end-points in assessment of cancer occurrence and progression.

Tumours of the liver.

One of the major debates in hepatocellular carcinogenesis at present is whether the hepatitis-B and -C viruses are directly carcinogenic or exert their effect indirectly by causing chronic necro-inflammatory hepatic disease, which in turn is responsible for malignant transformation of hepatocytes. This debate has been fueled by the observation that hepatitis C virus is a single-stranded RNA virus with no precedent for inducing cancer but with a marked propensity to cause chronic necro-inflammatory hepatic disease and by the findings in Chisari's transgenic mouse model, which suggest that severe and prolonged hepatocellular injury per se induces a proliferative response that progresses to tumour formation. Recent reports of a guanine to thymine mutation of the third base of codon 249 of the tumour suppressor gene, p53, in 50% of patients with hepatocellular carcinoma in regions of high aflatoxin exposure, and mutagenic experiments showing that aflatoxin B1 binds particularly to guanine residues in G-C-rich domains and that codon 249 is a preferred target have suggested a mechanism whereby aflatoxin might induce malignant transformation.