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Biomedical subjects

N A Habib

Publications and source records attributed to N A Habib.

At least 19 recordsLinked to original sources
PubMed2006

A modified radiofrequency-assisted approach to right hemihepatectomy.

AIMS: To evaluate a modified radiofrequency-assisted approach to right hemihepatectomy. METHODS: Following a bilateral subcostal incision and intraoperative ultrasonography, the liver was mobilized in the standard manner, and a cholecystectomy was performed. The portal vein was isolated, encircled, and ligated. After demarcating the liver parenchyma, coagulation necrosis was achieved using a radiofrequency-assisted device along the line demarcated for transecting the liver parenchyma. The actual transection of the liver parenchyma and the right portal vein was done using a surgical scalpel along the radiofrequency-coagulated line. The right hepatic vein was coagulated using the radiofrequency sealer or by stitching in the resection plane. The hepatic artery was not dissected and was sealed together with the bile ducts in the resection plane using the radiofrequency instrument. The hepatic vein was not divided. RESULTS: Between July 2005 and July 2006, a total of 49 liver resections were performed in our unit. Of these, the radiofrequency-assisted technique was used in 33 cases with metastatic disease; 14 of these cases had right hemihepatectomies, including 2 repeat resections. The mean operation time was 180min (range, 120-240min), and the average blood transfusion was 0.14U (range, 0-2U). Postoperatively, there was no morbidity, such as bleeding, infection, or biliary fistula, related to the liver resection technique, and no patients died as a result of surgery. In 8 out of the 14 right hemihepatectomies, a right-sided pleural effusion was observed; 3 of them required evacuation. CONCLUSION: This paper describes a modified radiofrequency-assisted hemihepatectomy, which allows one to obtain control of the portal blood flow going into the resected part of liver. The modified approach appears to be simple and safe.

Catheter Ablation↗
PubMed2005

Short- and-long term results of intraoperative radiofrequency ablation of liver metastases.

BACKGROUND: Surgical resection is the only therapeutic option with curative effect on malignant liver tumours, but in over 70% of cases, this is not a feasible option. A prospective study was performed to assess the short- and long-term effects of intraoperative radiofrequency ablation on unresectable liver metastases. PATIENTS: Between 1997 and 2001, 57 patients (mean age 61.9 years; range 31-83 years) with 297 unresectable liver metastases (colorectal adenocarcinoma, n=38; carcinoid tumour, n=4; malignant melanoma, n=3; other metastases, n=12) underwent intraoperative radiofrequency ablation. RESULTS: No mortality was observed in patients managed solely with radiofrequency ablation. Eight postoperative complications occurred in eight patients (14%). Three occurred when radiofrequency ablation was combined with resection. Of the 33 patients completely ablated, 30 patients are still alive and 21 are disease-free after a median follow-up of 18.1 months (range 2-43). Ten patients underwent more than one intraoperative radiofrequency ablation episode. Overall survival was 72.5% at 1 year and 52.5% at 3 years. Complete ablation and the number of lesions were significant independent prognostic factors for survival, with p<0.001 and p<0.0001, respectively. CONCLUSION: Radiofrequency ablation is a safe and effective option for patients with inoperable liver metastases without extra hepatic disease. Prospective controlled trials comparing the results of different treatments are required to assess which patients will benefit best from this emerging new treatment.

Adult↗
PubMed2003

Laparoscopic radiofrequency-assisted liver resection.

Laparoscopic liver resection has not yet gained wide acceptance among hepatic surgeons, mainly because of the difficulties encountered in dealing with possible intraoperative bleeding. A new technique of laparoscopic liver resection is presented. A 43-year-old man with a large and symptomatic hemangioma underwent a laparoscopic radiofrequency energy-assisted liver resection. After induction of pneumoperitoneum, four trocars were introduced and intraoperative ultrasonography and coagulative desiccation were performed along a plane of tissue 1 cm away from the edge of the lesion using the Cool-Tip radiofrequency probe and a 500-kHz, radiofrequency generator. The necrosed band of parenchyma then was divided and the specimen removed. The operative time was 300 min with a resection time of 240 min. The intraoperative blood loss was 75 ml. The postoperative course was uneventful and the patient was discharged on postoperative day 6. Laparoscopic radiofrequency-assisted liver resection is feasible, and with greater experience may contribute to the wider use of mini-invasive video-assisted liver surgery.

Adult↗
PubMed2003

Mucous cystadenoma of the appendix: is it safe to remove it by a laparoscopic approach?

Mucinous cystadenoma is an uncommon neoplasm of the appendix usually discovered intraoperatively. Its clinical significance lies in the possible rupture and consequent spillage of mucin into the peritoneal cavity, leading to pseudomyxoma peritonei. Even if laparoscopy has been successfully used to perform appendectomy, some concerns exist regarding its use in dealing with mucinous secreting lesions because of possible spillage of mucin during surgery. We report a case of mucous cystadenoma of the appendix, which was successfully removed using a laparoscopic approach. At a 12-month follow-up assessment, the patient was free of disease. We believe that the laparoscopic approach is safe if surgery can be performed without grasping the lesion, and if the specimen is removed through the abdominal wall using a bag. Conversion to laparotomy should be considered if the lesion must be traumatically grasped, or if the tumor clearly extends beyond the appendix.

Appendiceal Neoplasms↗
PubMed2002

A novel approach to gallbladder cancer in a Jehovah's Witness.

Transfusion of blood or blood products peri- or postoperatively is often necessary in patients undergoing liver resections for hepatic or biliary tract neoplasms. In Jehovah's Witnesses this inevitably poses a difficult dilemma for clinicians. A 66-year-old female Jehovah's Witness with a T1b gallbladder cancer was referred to our specialist unit for further treatment after having had a routine laparoscopic cholecystectomy in another hospital. Although an abdominal computed tomography scan preoperatively showed a normal liver with no evidence of regional lymph node involvement, histologically the tumor was found in the posterior wall of the gallbladder adherent to the liver bed and had a full thickness involvement of the muscular layer, raising suspicion of a local invasion into the liver bed. The patient, having refused liver resection, was treated with a laparoscopic radiofrequency ablation under intraoperative ultrasound guidance using a newly developed "cooled-tip" needle and a 500-kHz radiofrequency generator. A "zone of necrosis" measuring 3.5 cm in diameter was created in the liver bed and adjacent tissues. The procedure lasted 90 min with no blood loss. Postoperatively, the patient was discharged on the third postoperative day and remained disease free at the 9-month follow-up. Although the follow-up in this case was too short to determine the long-term result of this approach, we believe that this is a single unique case posing a challenging problem to clinicians for which radiofrequency ablation may have a role in offering an alternative to major resections.

Aged↗
PubMed2001

E1B-deleted adenovirus (dl1520) gene therapy for patients with primary and secondary liver tumors.

Clinical studies were performed with a recombinant mutant adenovirus with an E1B 55-kDa deletion, dl1520, to assess its toxicity and efficacy in patients with irresectable primary and secondary liver tumors. A phase I study showed that dl1520 was well tolerated when administered directly intratumorally, intraarterially, or intravenously up to a dose of 3 x 10(11) PFU. Ultrastructural examination of tissue showed the presence of adenovirus in cell cytoplasm around the nucleus and revealed two dissimilar end points of cell death after virus infection: a preapoptotic sequence and necrosis. A phase II study showed that the combination of dl1520 and 5-fluorouracil (5-FU), when infused into the hepatic artery, was well tolerated. Further improvement in the recombinant vector design will be needed in order to achieve better clinical response.

Adenoviridae↗
PubMed2001

Hepatic ischemia-reperfusion injury.

BACKGROUND: The morbidity associated with liver transplantation and major hepatic resections is partly a result of ischemia-reperfusion injury. DATA SOURCES: The entire world literature on the subject was searched via Medline. Keywords included reperfusion injury, transplantation, liver resection, nitric oxide, endothelin, cytokines, Kupffer cells, ischemic/ischaemic preconditioning, and nuclear factor-kappa B. CONCLUSIONS: An imbalance between endothelin and nitric oxide levels results in failure of the hepatic microcirculation at the onset of reperfusion. Activation of nuclear factor-kappa B in the liver promotes proinflammatory cytokine and adhesion molecule synthesis. These result in oxygen-derived free radical production and neutrophil recruitment, further contributing to cellular injury. Various therapeutic modalities acting on the above mediators have been successfully used to attenuate reperfusion injury in animal models of hepatic transplantation and resection. Application of the knowledge gained from animal models of hepatic ischemia-reperfusion to the clinical setting will improve the outcome of hepatic surgery.

Adenosine↗
PubMed2001

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

BACKGROUND/AIMS: A 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. METHODS: High-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. RESULTS: A 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. CONCLUSIONS: These 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.

Adult↗
PubMed2001

The cytotoxic effect of E1B 55-kDa mutant adenovirus on human hepatocellular carcinoma cell lines.

It has been suggested the E1B 55 kDa mutant adenovirus dl1520 can selectively kill p53-deficient human tumor cells. In this study, we examined the cytotoxic effect of dl1520 on nine human hepatocellular carcinoma (HCC) cell lines with different p53 genetic and functional status. The results showed that HCC cell lines with deleted or mutant p53 gene and reduced p53 transcriptional activities were more susceptible to dl1520-induced cytolysis. Hep3B (p53-null) and HepG2 (p53-wt) cells were arrested at G2/M phase when cytolysis occurred. Cyclin-dependent kinase inhibitor (CDKI) p21(Waf-1/Cip-1) was downregulated 24 hours after dl1520 infection in HepG2 cells and increased when cytolysis occurred. No p21 expression was detected in Hep3B cells. DNA fragmentation was found in both Hep3B and HepG2 cells after dl1520 infection. Bax expression increased in dl1520-infected HepG2 cells but not in Hep3B cells. Notably, three Bax-like proteins, molecular mass around 40 to 80 kDa, accumulated 48 hours after adenovirus infection in Hep3B cells but not in HepG2 cells. These results suggest that the susceptibility of HCC cells to dl1520-induced cytolysis is related to both p53 genotype and functional status, and is mediated by both cell cycle disturbance and apoptosis.

Adenoviridae↗
PubMed2000

New p53 mutations in hilar cholangiocarcinoma.

BACKGROUND: Inactivation of the tumour suppressor gene, p53, is the commonest genetic abnormality in human cancer. The study of the type of p53 mutation in a given tumour may provide prognostic information, clues to aetiology and become useful for therapeutics. MATERIALS AND METHODS: The molecular characterisation of p53 was performed by restriction analysis, denaturing gradient gel electrophoresis, and gene sequencing for exons 5-9. RESULTS: We report, p53 mutational analysis in exons 5-9 in 29 European patients with hilar cholangiocarcinoma who underwent attempted resection. Four patients (14%) showed somatic single nucleotide substitutions with amino acid changes (146, 163, 175, 158, and 175) with one showing mutations in two different positions involving a loss of two CfoI sites. All the mutations occurred in exon 5. Three patients had a germline polymorphism (10%) with a silent substitution in codon 213 (exon 6). CONCLUSIONS: The systematic screening for p53 mutations in European patients with hilar cholangiocarcinoma has shown that the type of mutation (except 175) is different and its incidence is much lower when compared to the pattern previously reported for intrahepatic cholangiocarcinoma in East Asian patients. A probable explanation is that the presence and type of p53 mutation is dependent on geographic and environmental factors which vary in different populations.

Adult↗
PubMed2000

Microsatellite instability and allelic imbalance in primary and secondary colorectal cancer.

BACKGROUND: Several studies of colorectal cancer have shown an association between the number and type of genomic defects and the stage of disease. A subset of colorectal tumours are due to inactivation of DNA mismatch repair genes and these tumours exhibit microsatellite instability. The aim of the present study was to compare and contrast the genomic defects present in both the primary and metastatic stages of the disease using microsatellite probes. METHODS: Modifications of the allelic profiles of 25 microsatellite regions were studied in a total of 85 colorectal tumours using fluorescent polymerase chain reaction (PCR) technology and subsequent direct analysis on an automatic sequencer. This approach was used because it allows the study of microsatellite instability and allelic imbalance. Stepwise logistic regression analysis was used to develop a model to predict whether the tumour was primary or secondary from the percentage of allelic imbalance. Subsequently, a group of 17 patients with primary colorectal tumours was analysed prospectively to test the proposed model. RESULTS: Six of 39 primary tumours showed microsatellite instability compared to 0 of 29 liver metastases (P = 0.03). Primary tumours showed significantly less allelic imbalance than liver metastases (P < 0.001). Three probes (d18s53, d9s158 and d10s191) were selected for use in a model to classify a tumour as primary or secondary on the basis of the degree of allelic imbalance. When tested prospectively this model had a specificity of 82%. CONCLUSIONS: The present study demonstrates the potential importance of using microsatellite probes both as a diagnostic tool and as a research technique to investigate the mechanisms of tumour progression. An important clinical finding is that none of the colorectal liver metastases showed microsatellite instability (0 of 29). This analysis also confirmed other work that has shown a direct relationship between the degree of allelic imbalance and the stage of disease.

Alleles↗
PubMed2000

Detection of adenovirus and initiation of apoptosis in hepatocellular carcinoma cells after Ad-p53 treatment.

Transcription of the p53 gene can regulate progression of apoptosis in a wide variety of tissues. Three categories of human hepatocyte culture have been used to show the initiation of apoptosis after treatment with p53-bearing adenovirus. Chang liver cells are derived from normal liver tissue and express native p53, whereas hepatocellular carcinoma (HCC)-derived cell lines were Hep3B (p53-deleted) and PLC/PRF/5 (p53-mutant). Cultures were infected with Ad-p53 (15 particles per cell; 36 hours), and after treatment, morphological changes in all cell categories were observed by electron microscopy. Infection was evident in the cytoplasm of all treated cell types: after entry across the plasma membrane viruses translocated and came to rest surrounding and adjacent to nuclei, cytoplasm proximal to nuclear membranes became dense with virus- and membrane-derived debris, but intact viruses did not enter nuclei. Apoptosis, recognized morphologically by characteristic chromatin and cytoplasmic condensation, occurred more frequently in HCC-derived cells, and the ultimate fate of apoptotic bodies was phagocytosis and degradation by neighboring cells.

Adenoviridae↗
PubMed2000

Respiratory infections in the traveler.

The growth of travel of recent years has been unprecedented and presents new challenges to health professionals worldwide. More travelers of diverse backgrounds are visiting exotic locales rarely encountered before. This poses new risks to health, in addition to potentially aiding the spread of emerging respiratory infections. Travelers such as immunocompromised individuals and members of ethnic minorities are at significant risk for travel-related infections. Respiratory illnesses are some of the most common infections affecting human beings, yet little information has been published on them in relation to travel. Multidisciplinary approaches and collaboration across different sectors are needed to address the many issues involved in travel-related respiratory infections. This article discusses some of the topical issues of respiratory tract infections occurring in travelers.

Humans↗
PubMed1999

A phase I/II study of hepatic artery infusion with wtp53-CMV-Ad in metastatic malignant liver tumours.

Colorectal cancer (CRC) is the second commonest cause of cancer death in the UK, with greater than 40% of these patients destined to die of the disease despite current medical management. Death is commonly due to liver metastases with sequelae including progressive liver dysfunction. Most patients with liver metastases present with tumours that are unresectable and incurable with existing therapies. The median survival for CRC patients after diagnosis with liver metastases is approximately 6 months or less. The human p53 gene is a tumour suppressor gene involved in the control of cell proliferation. Loss of wild-type p53 function is associated with the uncontrolled growth of many types of human cancers. The reintroduction and expression of wild-type p53 into p53 altered tumour cells has been shown to suppress tumour growth or induce apoptosis in both in vitro and in vivo models. In our experience greater than 50% of CRC tumours have p53 alterations. This study seeks to evaluate the safety, biological efficacy and the effectiveness of wtp53-CMV-Ad treatment which is a recombinant adenoviral vector containing the wild-type human p53 gene. It will be administered by infusion via the hepatic artery, for the regional gene therapy of malignant liver tumours. Study patients will have incurable metastatic (CRC) malignant tumours of the liver with evidence of p53 alteration in their liver tumours. In vitro studies have demonstrated p53-specific antiproliferative effects of wtp53-CMV-Ad on human liver tumour cells and in vivo studies have demonstrated p53-specific antiproliferative effects on human liver tumour cells. The vector Ad-p53 is a recombinant, replication-defective adenovirus based on adenovirus serotype 5. It contains a sequence encoding wild-type p53 whose expression is under the control of the human cytomegalovirus immediate early promoter-enhancer. This construct will be growth in 293 cells which contain the adenoviral E1A and E1B coding sequences which have been removed from the vector to render it replication defective. The study design is an open-label, non-randomised, single-dose, dose escalation Phase I/II clinical trial anticipated to involve a maximum of 19 patients. wtp53-CMV-Ad will be administered by infusion in a reservoir connected to the hepatic artery, for regional gene therapy (surgically implanted pump) in 3 escalating doses to successive cohorts of 3 patients each until the maximum tolerated dose is determined. Subsequently, 10 patients will be treated with this dose. Regional wtp53-CMV-Ad therapy will be administered as a single bolus infusion via hepatic artery catheter. The route of administration of wtp53-CMV-Ad via hepatic artery infusion is designed to maximise gene therapy exposure to the malignant tumours while minimising exposure to normal tissues outside the liver. The clinical protocol is designed to monitor treatment toxicity. Another objective is to evaluate the biological efficacy, including efficiency and stability of gene transfer by analysis of tumour tissues following therapy. As an important part of this objective the pharmacokinetics of wtp53-CMV-Ad will be studied. Clinical evidence of anti-tumour efficacy will also be collected. In addition, the safety and efficacy of different doses levels of wtp53-CMV-Ad will be studied.

Adenoviridae↗