Interstitial laser coagulation for hepatic tumours.
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Humans↗
Biomedical subjects
N A Habib
Publications and source records attributed to N A Habib.
Characterization of p53 mutations in colorectal liver metastases and correlation with clinical parameters.
The presence and type of mutations of the p53 tumor suppressor gene were determined in 40 patients undergoing curative hepatic resection for metastatic colorectal carcinoma. This represents the largest series in the literature on the screening of p53 mutations for liver metastases. The analysis was performed in exons 5-9 by denaturing gradient gel electrophoresis followed by direct sequencing. Forty-five percent of tumors showed mutation in p53, and this was observed only in exons 5-8. Mutations at codon positions 167, 196, 204, 213, 245, 281, 282, 286, and 306; deletion of codon 251 and of the first nucleotide of codon 252; and Leu residue (CTC) insertion downstream codon 252 are reported for the first time in colorectal liver metastasis. Mutations at codon positions 163, 248, and 273 have been reported previously. Correlation of p53 status with clinical parameters showed that patients with mutated p53 had a statistically higher number of lesions when compared with patients with wild-type p53 (P<0.050). In particular, of patients with mutated p53, 41% had three or more metastases compared with 14% of patients with wild-type p53. Synchronous metastases were present in 70% of the patients with p53 mutations and in only 29% of patients with wild-type p53 (P<0.025). In addition, patients with p53 mutations are more likely to develop recurrence (73%) compared with patients with wild-type p53 (33%; P<0.001). Other factors considered, including preoperative carcinoembryonic antigen level, bilobar distribution, and size of the lesion(s), did not show significant correlation with p53 status. These results suggest that p53 status might be an important prognostic indicator to predict the pattern and likelihood of treatment failure after hepatic resection.
Adult↗
p53 and gene therapy for hepatocellular carcinoma.
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Apoptosis↗
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).
Adolescent↗
Systemic cytokine response to hepatic resections under total vascular exclusion.
OBJECTIVE: To investigate the systemic cytokine response to major liver surgery as the basis for assessing potential new treatments. DESIGN: Open prospective study. SETTING: University hospital, UK. SUBJECTS: Thirteen patients undergoing elective hepatic resections that involved total vascular exclusion of the liver. INTERVENTIONS: Blood samples were taken preoperatively, during the operation, and during the first four postoperative days. Concentrations of endotoxin, interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNFalpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) were measured. RESULTS: Endotoxin concentrations were raised in 3/13 patients before operation and in 6 patients during the postoperative period. TNFalpha concentrations were undetectable. IFN-gamma and IL-1 responses followed a low and inconclusive pattern. IL-6 was significantly increased from 6 hours after operation to the third postoperative day, peaking at 699 (+/-277) pg/ml at 24 hours (p < 0.01). The two patients who died had the highest postoperative concentrations of IL-6. CONCLUSIONS: There is a pronounced systemic response to hepatic resection under total vascular exclusion that is reflected by the increase in IL-6 concentration and correlates with the operative blood loss and postoperative outcome. This might be used as an indicator of the response to specific treatments in this type of surgery. Treatments that minimise the IL-6 response to major hepatic resection may be of value.
APACHE↗
Aggressive surgical management of fibrolamellar hepatocellular carcinoma in puberty.
Extensive right hepatectomy and replacement of the invaded inferior vena cava were performed in a 14-year-old girl with fibrolamellar liver carcinoma. Despite the graft thrombosis the patient was discharged on the 50th post-operative day. After 3 years a solitary lung metastasis was resected and the patient remains with no sign of intra-abdominal or intrathoracic recurrence.
Adolescent↗
Overexpression of hepatic prothymosin alpha, a novel marker for human hepatocellular carcinoma.
Identification of gene products exclusively or abundantly expressed in cancer may yield novel tumour markers. We recently isolated a number of cDNA clones, including alpha-prothymosin, from rat hepatocellular carcinoma (HCC) using a subtraction-enhanced display technique. Alpha-Prothymosin is involved in cell proliferation and is regulated by the oncogene c-myc in vitro. In the present study, we analysed alpha-prothymosin gene expression and its correlation with c-myc in patients with HCC, cirrhosis and adenoma and in normal controls. Hepatic alpha-prothymosin messenger RNA (mRNA) levels were two- to 9.2-fold higher in tumoral tissues than in adjacent non-tumoral tissues in 14 of 17 patients with HCC, regardless of coexisting cirrhosis and viral hepatitis. No marked difference in alpha-prothymosin mRNA levels was present in patients with adenoma and hepatic cirrhosis and in healthy controls. The c-myc mRNA amounts were two- to fivefold increased in 11 of 17 patients with HCC and correlated significantly with those of alpha-prothymosin (P < 0.001). In situ hybridization revealed that increased alpha-prothymosin mRNA was localized in the tumour nodules of the patients with HCC. These data suggest that overexpression of alpha-prothymosin in HCC patients, correlated with c-myc, is possibly involved in the tumorigenic process and may be a novel molecular marker for human HCC.
Adenoma↗
Wild-type p53 induces apoptosis in Hep3B through up-regulation of bax expression.
We demonstrated that introduction and expression of wild-type p53 gene in the human hepatocellular carcinoma cell line, Hep3B, resulted in up-regulation of both p21WAF1/CIP1 and bax gene expression and apoptosis. This cell line contains integrated hepatitis B virus sequences and lacks the expression of both p53 and retinoblastoma tumor suppressor genes because of deletions. Our results suggest that whereas an increased level of bax expression mediates apoptosis, an increased level of p21WAF1/CIP1 expression does not induce arrest of cell growth, presumably because of the deletion of the retinoblastoma gene. This study also confirms reported observations that p53 is a tumor suppressor gene, which induces apoptosis in malignant cells that lack normal p53 activity because of mutation, deletion, or inactivation of the gene by the presence of oncogenic viral proteins.
Apoptosis↗
Fibrolamellar hepatocellular carcinoma: results of partial liver resection.
AIM: To assess the results of partial hepatic resection in the treatment of fibrolamellar hepatocellular carcinoma. PATIENTS AND RESULTS: We present six cases of Fibrolamellar hepatocellular carcinoma treated by partial hepatic resection. There were five females and one male with a mean age of 20 (2.6) yr. Five patients were stage IVA and 1 IVB based on the Union International Against Cancer Classification. Two patients, due to recurrent disease, needed further pulmonary resection and a hilar lymphadenectomy. All six cases underwent major resection, three with vascular reconstruction. No operative mortality was recorded; half of the patients displayed some degree of morbidity. One patient died six months after the operation and the rest are alive at 78, 41, 24, 12 and 9 months. We believe that even in advanced cases, an aggressive surgical policy even with vascular reconstruction is justified in patients with fibrolamellar hepatocellular carcinoma.
Adolescent↗
Effect of total hepatic vascular exclusion during liver resection on hepatic ultrastructure.
The aim of this investigation was to observe ultrastructural changes in the liver in response to warm ischemia during liver surgery. In 11 noncirrhotic patients, hepatic resection was performed under total vascular exclusion (TVE). The mean duration of warm ischemia was 28 minutes (range 16-48 minutes). Three specimens were taken from each patient: before clamping, at the end of TVE, and after reperfusion. Biopsy specimens were studied by light microscopy and by transmission electron microscopy (EM). At the end of the ischemic phase sinusoids were collapsed with resultant loss of normal hepatic architecture. Morphological changes to hepatocytes included focal chromatin condensation at the nuclear margins, distended nuclear envelope, and swelling of both mitochondria and endoplasmic reticulum. After reperfusion these changes reversed. The phenomenon of sinusoidal and hepatocellular recovery after TVE was seen in all the cases of this study, irrespective of age, sex, disease, type and severity of surgical intervention, and duration of TVE. It can be concluded that TVE over a period of 48 minutes has no irreversible deleterious effects on the ultrastructure of the noncirrhotic liver.
Adult↗
The use of hypothermia and circulatory arrest to control intraoperative bleeding from the inferior vena cava.
Bleeding from the suprahepatic inferior vena cava (IVC) was encountered in a patient undergoing repeat liver resection for the fourth time due to a recurrence of colorectal liver metastases. Bleeding was observed from an IVC tear above the liver and it was not possible to control it with traditional clamping procedures including total vascular exclusion (a suprahepatic clamp). Hypothermia, cardioplegia, and circulatory arrest were all required to control the bleeding. The inferior vena cava was reconstructed with a pericardial patch. The patient recovered well and was discharged on the 14th postoperative day.
Colorectal Neoplasms↗
Preliminary report: the short-term effects of direct p53 DNA injection in primary hepatocellular carcinomas.
A pilot study, to assess the therapeutic potential of percutaneous injection of wild-type p53 (wt-p53) in five patients with primary hepatocellular carcinoma is reported. Three of the five patients showed objective tumor response with reduction of the tumor volume on computed tomographic (CT) scan measurements as well as a significant fall of serum alphafetoprotein. Much further work will be needed to elucidate the mechanism of action.
Adult↗
Combined pulmonary tumour embolectomy and extended right hepatectomy with inferior vena cava resection for advanced hepatocellular carcinoma.
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Carcinoma, Hepatocellular↗
Loss of heterozygosity in liver tumours.
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Colorectal Neoplasms↗
Repeated resection for malignant liver tumours.
Fifteen repeat hepatic resections were performed on 12 patients with either recurrent or residual malignant tumours of the liver. Of these, one patient underwent three repeat resections and another underwent two. Five had primary liver liver tumours and seven had liver metastases. Planned, 'staged', repeat resections were performed on three patients because of multiple deposits of tumour, cirrhosis or extensive disease at initial presentation. There was no operative mortality. The period of follow-up from the time of repeat sections ranged between 4 months and 36 months during which two patients died from recurrent disease. The mean survival after the repeat resection was 16.8 months (range 4-36 months). Although technically demanding, repeat hepatectomy is feasible and provide similar benefits.
Aged↗
Early mortality in 100 consecutive liver resections in 96 patients with benign and malignant liver tumours.
This report describes the mortality in 100 liver resections performed in 96 patients for seven benign and 93 malignant liver tumours. Repeat hepatectomy was performed in four patients who developed recurrences after the first liver resection. Two patients died within 30 days. The first was a 67-year-old man who died on the 2nd postoperative day from cardiac failure. The second was a 69-year-old man who died on the 4th postoperative day with liver failure caused by hepatic vascular ischaemia. There were four other hospital deaths at days 33, 40, 45 and 50. A 65-year-old lady died on day 40 from sepsis caused by small bowel infarction. A 30-year-old man died on the 33rd postoperative day owing to liver failure from accelerated hepatic lymphoma spread. A 71-year-old diabetic lady died on the 45th postoperative day from sepsis caused by an untreated subphrenic abscess. A 65-year-old lady died on day 50 from systemic candidiasis after adult respiratory distress syndrome (ARDS). Further reduction in operative mortality could be achieved by better patient selection. Liver resection still remains a major operation, but has become a safe surgical procedure.
Adolescent↗
Partial characterization of a cDNA for human stearoyl-CoA desaturase and changes in its mRNA expression in some normal and malignant tissues.
A segment of 712 bases coding for part of the human stearoyl-CoA desaturase gene was made by polymerase chain reaction (PCR) using primers based on published rat cDNA sequences. The human PCR product was confirmed by DNA sequencing. It was next cloned into a vector from which anti-sense, highly radioactive RNA transcripts were made in vitro using T7 polymerase. The transcripts were used to probe desaturase mRNA in a number of human tumour and control tissues, using a very sensitive solution hybridization/RNase protection assay. Increased desaturase mRNA levels were found in colonic and oesophageal carcinomas and in hepatocellular adenoma; however, no consistent trend was seen in hepatocellular carcinoma. It is suggested that certain classes of tumour may exhibit increased levels of desaturase mRNA.
Amino Acid Sequence↗
Chromosome allele loss in colorectal liver metastases and its association with clinical features.
Molecular genetic changes are better characterized in colorectal carcinoma than in other common adult tumours. Consistent allele losses, or loss of heterozygosity (LOH), on chromosomes 5q, 17p and 18q have been well established. These changes are associated with the prognosis of the disease. Little is known of such changes in liver metastases of colorectal origin. The extent of allelic loss and its association with clinical features were investigated in 19 patients with colorectal liver metastases by using 24 probes to detect restriction fragment length polymorphism. A high frequency of LOH on chromosomes 5q, 17p and 18q was found in these secondary tumours. No consistent loss has so far been shown in any other chromosome. The frequency of allele loss correlated significantly with prognostic features such as the number and size of liver secondaries (P < 0.005), metastasis to the lymph nodes (P < 0.01) and curative or palliative operation (P < 0.02).
Alleles↗