Ragai R. Mitry

Clinical short-term results of Radiofrequency ablation in primary and secondary liver tumors

BACKGROUNDnRadiofrequency ablation (RFA) is emerging as a new therapeutic method for management of solid tumors. We report here our experience in the use of this technique for management of primary and secondary unresectable liver cancers.nnnMETHODSnThirty-five patients with liver cancers were considered not suitable for curative resection at presentation: 8 with primary hepatocellular carcinoma ([HCC] 6 HCC and 2 fibrolamellar); 27 with metastatic liver cancer (17 colorectal carcinoma and 10 others). They were treated either with radiofrequency heat ablation (Radionics Europe N.V., Wettdren, Belgium) alone percutaneously and/or intraoperatively or in conjunction with surgical resections. The quality of RFA was based on the subjective feeling of whether the tumor was completely destroyed or not. The effectiveness of RFA was assessed according to clinical findings, radiographic images, and tumor markers at follow-up.nnnRESULTSnIn 8 primary liver cases, 4 patients with a high level of alpha fetoprotein (AFP) benefited from the RFA with a 83.3% to 99.7% reduction of AFP. One with fibrolamellar hepatocellular carcinoma died 2 months after an incomplete percutaneous RFA from recurrence. The rest all had stable disease at the time of follow-up (mean 10.4 months). In patients with colorectal liver metastases, there were 4 deaths: 1 patient died postoperatively on the 30th day from a severe chest infection having shown a considerable reduction of carcinoembryonic antigen level (CEA, 8 versus 36 microg/L); 3 died from local and systemic disease, 1 at 12 months and 2 at 1 month, having had an incomplete RFA. The others had stable disease at follow-up (mean 7.6 months). Five patients underwent liver resections successfully with the application of RFA for residual lesions in the remaining contralateral lobe. In 10 patients with other liver tumors, 7 patients had stable disease at follow-up (mean 13.4 months); 1 patient had evidence of local and systemic recurrence 10 months after surgical resections with the intraoperative RFA and 2 patients died of systemic recurrence of disease 3 and 6 months after RFA alone. Two patients had liver resections in conjunction with the intraoperative RFA. The mean follow-up in our series was 8.5 months.nnnCONCLUSIONnRadiofrequency heat ablation is useful as a primary treatment for unresectable liver cancers. The procedure can be used to treat the small residual tumor load in the contralateral lobe following liver resection in those considered unresectable at the first presentation. This new therapeutic strategy seems to increase surgical resectability in patients judged unresectable.

p53 mutation is a poor prognostic indicator for survival in patients with hepatocellular carcinoma undergoing surgical tumour ablation

Forty-two patients with hepatocellular carcinoma (HCC) were resected and their tumours were analysed for p53 mutations by GC-clamped denaturing gradient gel electrophoresis (DGGE), single-strand conformation polymorphism (SSCP) and gene sequencing. All the exons have been analysed in this study. Eight of 12 HCCs with cirrhosis due to viral hepatitis and the two patients with sarcomatoid changes displayed p53 mutations. In contrast, no mutation was observed in the fibrolamellar variant (n = 9), non-cirrhotics (n = 13) and alcoholic cirrhosis (n = 6). The mutations observed were in exons 5-8. Two mutations were observed in codons 136 and 213 as well as a T insertion between residues 156 and 157 (exon 5) and these are reported for the first time in HCC. Likewise, the silent mutation polymorphism in codon 213 was noticed in 3 of the 42 patients. Survival analysis of these patients after surgery showed the mean and median survival in patients with wild-type p53 to be 60 and 43 months respectively. In the group with p53 mutations, the mean and median survival was 15 and 12 months. The difference was statistically significant (P= 0.003).

Profiling the adult human liver transcriptome: analysis by cDNA array hybridization

BACKGROUND/AIMSnA comprehensive profile of genes expressed at the mRNA level (transcriptome) in human liver tissue is important for elucidating the pathogenesis and treatment of hepatic diseases. The recent development of cDNA array hybridization allows the parallel monitoring of thousands of genes expressed in a single organ.nnnMETHODSnHigh-density microarrays containing 4043 known and unique human cDNA gene targets were used to quantitatively analyze the expression of genes in human livers. Expressed gene transcripts were classified by function and listed with information of their chromosomal positions. Computational analysis was used to cluster genes according to similarity in pattern of gene expression.nnnRESULTSnA total of 2418 unique gene transcripts were detected in five liver specimens. Through relational database analysis, we determined 1212 genes that were commonly expressed in 4 of the five liver specimens. Furthermore, analysis of the total 2418 expressed genes by self-organizing maps and hierarchical clustering unexpectedly revealed a genomic acute phase response in two of the liver specimens.nnnCONCLUSIONSnThese findings represent a comprehensive preliminary molecular index of genes transcribed in the adult human liver. The information may serve as a resource for speeding up the discovery of genes underlying human hepatic diseases.

Gene Therapy for Liver Tumours

Liver tumours are among the most commonmalignancies worldwide. The international incidenceof the disease is about l million cases per year (male:femalc, 4: 1 ). These include primary and secondarytumours. Cancer is known to be a genetic disease thatinvolves the alteration of activity of the products of atleast 2 genes, due to mutation (s) and/or otherfactors, e. g., the presence of viral oncoproteins. Thegenes most affected are the tumour suppressor genes

p53 and Gene Therapy for Hepatocellular Carcinoma

In the 1990’s, the world has witnessed some 50 million deaths. Acute conditions such as infection and injury (including war) were the most common causes of death in the young. Chronic conditions such as ailments in the elderly were responsible for the deaths of some 30 million patients. Today, most deaths are due to cardiovascular accidents and the second most common cause of deaths is cancer. Some 6 million people die of cancer each year. Lung cancer is still the most common, followed by stomach, liver, colorectal, esophagus etc. Most of these patients develop liver metastases. Consequently, the liver is the most common target organ in patients with cancer.

Clinical Protocol for p53 Gene Therapy for Liver Tumors

This chapter is intended to help other workers with the preparation of human gene therapy proposals. What follows is an abridged version of a protocol describing the use of gene replacement with p53 for liver tumors. This was submitted to the Gene Therapy Advisory Committee (GTAC) of the Department of Health (United Kingdom). This is the first trial to be approved by GTAC for gene therapy of liver tumors in humans.

Direct DNA Injection (p53) into HCC Tumors

Liver tumors, specially HCC, are among the most common malignancies in the world, and their annual world incidence is about 250,000 cases, with a male to female ratio 4:1 (1). HCC is one of the most important neoplasms in tropical and subtropical regions, particularly among the sub-Saharan African black population and ethnic Chinese (2). The prognosis is very poor, and patients with advanced tumors are unlikely to survive 3 mo (3). Most HCC cases are beyond radical resection when detected. All other forms of the currently available therapies are rarely beneficial (2).

p53 Plasmid Preparation and Techniques for Analysis of Gene Transfer and Expression.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer death worldwide and is especially prevalent in certain areas of Africa and Asia. The most important etiological factor is infection with the hepatitis B or C virus. Treatment is generally unsatisfactory as the majority of patients are not suitable for surgical resection and chemotherapy is not particularly effective.