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F C Hamdy

Publications and source records attributed to F C Hamdy.

At least 37 records · Page 2Linked to original sources
PubMed2003

FGF8 isoform b expression in human prostate cancer.

Overexpression of fibroblast growth factor 8 (FGF8) mRNA has been previously described in prostate cancer. Of its four isoforms, FGF8b is thought to be the most important in carcinogenesis. We hypothesised that immunodetection of FGF8b in archival prostate cancer specimens is of potential prognostic value. Using a selected cohort of prostate tumours from transurethral (n=30) and radical prostatectomies (n=59), an optimised protocol for FGF8b immunoreactivity was used to corroborate expression with clinical parameters. No expression was observed in benign prostates (n=10). In prostate cancer, immunoreactivity was localised to the malignant epithelium with weak signals in the adjacent stroma. Expression of FGF8b in stage T1 and T2 cancers were 40 and 67%, respectively. In contrast, FGF8b expression was present in 94% of T3 and 100% of T4 cancers. By histological grade, FGF8b was found in 41% of low-grade cancers (Gleason score 4-6), 60% of intermediate-grade cancers (Gleason score 7 and 92% of high-grade cancers (Gleason score 8-10). The intensity of expression was significantly associated with stage (P=0.0004) and grade (P<0.0001) of disease. We further hypothesised that FGF8b overexpression resulted from enhanced transcription and translation rather than from abnormalities involving the FGF8 gene locus. This was tested by means of fluorescent in situ hybridisation in 20 cancer specimens to map the FGF8 gene locus. FGF8 gene copy number in benign and malignant nuclei was found to be similar (2.33+/-0.57 and 2.0+/-0.81, respectively P=0.51). Based on these findings, we propose a multicentre study on cohorts of patients to further evaluate FGF8b as a potential prognostic marker in prostate cancer.

Fibroblast Growth Factor 8↗
PubMed2003

Effectiveness and cost-effectiveness of prognostic markers in prostate cancer.

This paper demonstrates how economic modelling can be used to derive estimates of the cost-effectiveness of prognostic markers in the management of clinically localised and moderately graded prostate cancer. The model uses a Markov process and is populated using published evidence and local data. The robustness of the results has been tested using sensitivity analysis. Three treatment policies of 'monitoring' (observation), radical prostatectomy, or a selection-based management policy using DNA-ploidy as an experimental marker, have been evaluated. Modelling indicates that a policy of managing these tumours utilising experimental markers has an estimated cost per quality-adjusted life year (QALY) of pound 12 068. Sensitivity analysis shows the results to be relatively sensitive to quality-of-life variables. If novel and experimental markers can achieve specificity in excess of 80%, then a policy of radical surgery for those identified as being at high risk and conservative treatment for the remainder would be both better for patients and cost-effective. The analysis suggests that a radical prostatectomy treatment policy for the moderately graded tumours (Gleason grades -7) modelled in this paper may be inferior to a conservative approach in the absence of reliable prognostic markers, being both more costly and yielding fewer QALYs.

Cost-Benefit Analysis↗
PubMed2003

Recent trends in the use of radical prostatectomy in England: the epidemiology of diffusion.

OBJECTIVE: To describe recent trends in the use of radical prostatectomy (RP) in England, as there is currently no consensus on the most effective treatment for localized prostate cancer, although RP is the treatment of choice among urological surgeons for men aged < 70 years. METHODS: Routine data were assessed to establish the number of RPs performed in England in 1991-99. Age-standardized operation rates were compared by region and socio-economic group, and the geographical spread of use mapped. RESULTS: The number of RPs performed annually increased nearly 20-fold between 1991 and 1999. Rates of surgery were greatest in the London National Health Service (NHS) regions and lowest in the Trent region. Outside London, the risk of surgery in a NHS hospital was significantly greater for men living in the least deprived areas; in London this trend was reversed. CONCLUSION: Rapid increases in the use of RP showed marked regional variations, most likely related to access to prostate-specific antigen testing and the location of surgeons able to carry out radical surgery. By 1999, a third of procedures were still being undertaken in 'low-volume' hospitals, with implications for the quality of care and outcomes. Crucially, these developments occurred in the absence of robust information about the effectiveness of RP. Recent funding of a randomized trial of treatment options in this area is welcome, but wider questions remain about the timing of the evaluation of surgical technologies.

Aged↗
PubMed2002

Electrical impedance spectroscopy and the diagnosis of bladder pathology: a pilot study.

PURPOSE: Carcinoma in situ is an aggressive form of bladder cancer with a high propensity for invasion if left untreated. On cystoscopy these flat lesions cannot be differentiated from other erythematous, potentially benign areas and they require biopsy for definitive diagnosis. Other methods of detecting carcinoma in situ remain experimental. We assessed the effectiveness of electrical impedance spectroscopy, a method that measures the variation of electrical current flow with frequency through the mucosa, for differentiating various pathological changes in the urothelium. MATERIALS AND METHODS: We obtained 250 impedance measurements immediately after resection in 35 cystectomy specimens using a custom designed probe. Three consecutive readings were recorded per point to assess reproducibility and punch biopsy was done at the measurement site. RESULTS: Changes in the urothelium were classified histologically into 7 subgroups according to the degree of edema and inflammation. Electrical impedance spectroscopy measurements were able to separate benign and malignant changes when tested as a group (p <0.001), although some individual points overlapped. Edema also had a significant effect on tissue impedance (p <0.001). CONCLUSIONS: Using measurements we established patterns of electrical impedance in the human bladder. Early results suggest that this minimally invasive technique is able to differentiate benign and malignant bladder pathologies. However, it requires further refinement and evaluation at lower frequencies, where the greatest impedance difference in benign and malignant tissues is expected.

Adult↗
PubMed2002

Electrical impedance spectroscopy (EIS) in the urinary bladder: the effect of inflammation and edema on identification of malignancy.

Previous studies have shown that tetrapolar electrical impedance spectroscopy measurements can identify cervical interstitial neoplasia with the same sensitivity and specificity as cervical smears. In the urinary bladder, the same technique yields significant differences (p < 0.05 at seven frequencies between 9.6 and 614 kHz) between normal and malignant urothelium, but is unable to classify individual measurements. Detailed histological examination demonstrates that inflammation and edema--both of which are common in abnormal urothelium--alter the impedance spectrum significantly in opposing directions. Consideration of morphological changes in abnormal urothelium suggests alternative measurement strategies.

Carcinoma in Situ↗
PubMed2001

Prognostic and predictive factors in prostate cancer.

Prostate cancer is a major public health problem in the Western world, and the second most common male malignancies in the European Union. Detection of the disease is possible at an early stage, using serum prostate specific antigen measurement and prostatic biopsies. To date, however, screening for prostate cancer has not been shown to be of benefit to patients in improving outcome. This is compounded by uncertainties surrounding treatment efficacy, as more men appear to die with prostate cancer than from it. Studies addressing these issues are underway in Europe and the U.S.A. Clinicians are currently unable to advise their patients with any degree of certainty as to the appropriateness of treatment for prostate cancer, because of their inability to differentiate tumours that will progress from those that will remain quiescent. This article reviews the various clinical, pathological and experimental markers available, and their value in providing prognostic information, which may assist clinicians and patients in making management decisions. Further research is still required to understand the biological behaviour of prostate cancer and to assess the value of screening and treatment efficacy in order to advise patients, clinicians and health care systems accordingly.

Apoptosis↗
PubMed2001

Prostate specific antigen: biology, biochemistry and available commercial assays.

Prostate specific antigen (PSA) is the marker of choice in the management of prostate cancer. However, PSA is not a simple molecule, existing in the serum in five isoforms and a number of molecular configurations and complexes. The elucidation of the biochemistry of PSA has increased the potential use of the marker in the diagnosis of prostate malignancy. This review summarizes the clinical use of PSA in the management of prostate disease and the assays available in the UK. Assay calibration in relation to the World Health Organization 1st International Standard for Prostate Specific Antigen (90:10) has increased conformity between the various commercial assay kits, and the non-equimolar kits have largely been superseded or withdrawn. Special reference is made to evaluations performed on behalf of the Medical Devices Agency of the Department of Health.

Adenocarcinoma↗
PubMed2000

Localization and quantification of mRNA for matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in human benign and malignant prostatic tissue.

BACKGROUND: The family of matrix metalloproteinases (MMPs) has been shown to be involved in proteolytic degradation of the extracellular matrix, which is an essential step in tumor invasion and metastasis. MMPs are tightly regulated by the levels of active enzymes and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). MMP-2 and its ratio to TIMP-2 have been associated with tumor recurrence and progression in a number of human malignancies. METHODS: We examined the relationship between MMP-2 and TIMP-2 mRNA expression in 42 men with malignant (n = 32) and benign (n = 10) prostates using nonisotopic in situ hybridization and Northern blot analysis. RESULTS: mRNA for MMP-2 and TIMP-2 was localized to the malignant epithelial cells of both high- and low-grade tumors in the periphery of the glands and in areas of extracapsular involvement, and to the glandular epithelium in the benign prostates. Using Northern blot analysis, the mean MMP-2 to TIMP-2 ratio was approximately one in the benign prostates and low-grade and -stage cancers. The MMP-2 to TIMP-2 ratio increased to 3.3 in the high-grade and 2.8 in the high-stage tumors. CONCLUSIONS: The results suggest a close association between MMP-2/TIMP-2 expression and local tumor invasion, with a disruption in expression of the two genes leading to disease progression. Future studies should focus on the activity of these enzymes and on the ratio of enzyme/inhibitor expression, which may become a useful prognostic marker in prostate cancer.

Blotting, Northern↗
PubMed2000

Unanswered questions in screening for prostate cancer.

Prostate cancer fulfils some of the conditions required of a disease that might be managed by population screening. In a cohort of 50- to 60-year-old men, carrying out a rectal examination and prostate specific antigen (PSA) test will detect clinically suspicious areas within the prostate in approximately 5%, and approximately 10% will have a raised PSA. We are however unsure which of the prostate cancers that are known to be present in approximately 30-40% of men aged over 60 years will be detected. Eventually after such screening, around 4% of men with an otherwise normal prostate will be found to have prostate cancers. The use of rectal examination may increase the number of tumours found, but will reduce compliance. The use of free/total PSA ratios will reduce the number of unnecessary biopsies at the expense of missing some tumours. Of more concern, we remain uncertain how effective aggressive local treatment is in altering the natural history of the disease. The risk of a 50-year-old man with a 25 year life expectancy of having microscopic cancer is 42%, of having clinically evident cancer is 9.5%, and of dying of prostate cancer 2.9%. Only a small proportion of cancers known to be present become clinically evident: more men die with prostate cancer than of it. Screening will identify some men with cancer who will not benefit from treatment. It is unclear whether screening would be followed by a reduction in morbidity and mortality. Recent data suggest a screening effect has been observed in the USA with: an increase in incidence, a decrease in men with distant metastases. The small decrease in mortality recently observed (many times smaller than the increase in incidence) may be confounded by inappropriate 'attribution' of cause of death, the detection of men with better prognosis distant metastatic disease responsive to hormonal ablation and changes in social factors such as diet. Future changes may incorporate molecular markers that might aid identification of men best treated aggressively because of a risk of progression. Tests to identify genetic pre-disposition may also allow targeted screening. New treatments and early chemoprevention or dietary strategies will again shift the ground on which these arguments are being rehearsed. The most urgent evidence required concerns the effectiveness of treatment strategies.

Cost of Illness↗
PubMed2000

Bone morphogenetic protein-6: potential mediator of osteoblastic metastases in prostate cancer.

The mechanisms by which prostate cancer metastasizes to bone with a strong osteoblastic reaction remain poorly understood. Several factors have been previously implicated, including transforming growth factor-beta, fibroblast growth factors, endothelin-1 and bone morphogenetic proteins (BMPs). BMP-6 expression has been shown exclusively in the malignant epithelial cells of prostate cancers that have metastasized, but not in organ confined disease. Expression of BMP-6 in radical prostatectomy specimens has been shown to correlate with increased recurrence rates and decreased survival. This article presents the results of work by the authors' group in this field and a current literature review. Prostate Cancer and Prostatic Diseases (2000) 3, 283-285

Journal Article↗
PubMed2000

Neural network analysis of clinicopathological and molecular markers in bladder cancer.

PURPOSE: To evaluate retrospectively the ability of an artificial neural network (ANN) to predict bladder cancer recurrence within 6 months of diagnosis and stage progression in patients with Ta/T1 bladder cancer, and 12-month cancer-specific survival in patients with T2-T4 bladder cancer. MATERIALS AND METHODS: Data were analyzed using a NeuralWorks Professional II/Plus software package. The input neural data consisted of clinicopathological and molecular characteristics. Distinct patient groups were used for the prediction of stage progression and tumor recurrence in Ta/T1 bladder cancers, and 12-month cancer-specific survival for patients with T2-T4 tumors. ANN predictions were compared with those of four consultant urologists. RESULTS: The accuracy of the neural network in predicting stage progression and recurrence within 6 months for Ta/T1 tumors and 12-month cancer-specific survival for T2-T4 cancers was 80%, 75% and 82% respectively; with corresponding figures for clinicians being 74%, 79% and 65%. On restricting the validation subset to patients with T1G3 tumors in relation to stage progression, the sensitivity of the ANN analysis increased to 100% with a specificity of 78% and an overall accuracy of 82%. The performance of the ANN in predicting stage progression in T1G3 tumors was significantly higher than that of clinicians (p = 0.25 for the ANN and p = 0.008 for clinicians, McNemar test). CONCLUSIONS: Data analysis using an ANN has been shown to be a useful adjunct in predicting outcomes in patients with bladder cancer and out-performs clinicians' predictions of stage progression in the high risk group of patients with T1G3 disease.

Biomarkers, Tumor↗
PubMed1999

The effects of transurethral resection and cystoprostatectomy on dissemination of epithelial cells in the circulation of patients with bladder cancer.

This study was undertaken to evaluate the risk of haematogenous dissemination of epithelial cells induced by endoscopic resection and/or cystoprostatectomy for transitional cell carcinoma of the bladder. Thirty-three patients were studied. Thirty-one had different stages and grades of bladder cancer and two patients had benign bladder conditions. Twenty-five cancer patients required transurethral resection of their bladder tumour. Of those, 20 had superficial disease (pTaG1-G2: n = 19; pT1G2: n = 1) and five had muscle invasive tumours (pT2G3: n = 2; pT3aG3: n = 1; pT4G3: n = 2). Five patients underwent radical cystoprostatectomy for muscle invasive cancers (pT2G3: n = 3; pT3bG3: n = 1; pT4G3: n = 1) and one man received chemotherapy for metastatic disease. Venous blood (10 ml) was obtained from the antecubital fossa in each patient, before and 1-2 h after completion of surgery, and prior to treatment in the metastatic patient. An indirect immunocytochemical technique was used to detect circulating epithelial cells after centrifugation on Ficoll gradient and fixation of mononuclear cells on slides, using a monoclonal antibody directed against three cytokeratins: CK8, CK18 and CK19. Circulating epithelial cells were detected only in the patient with metastatic disease. None of the other patients had evidence of epithelial circulating cells before or after surgery. The results suggest that irrespective of disease stage and grade, neither endoscopic nor open bladder surgery leads to detectable dissemination of urothelial cells in the peripheral circulation. These procedures are therefore unlikely to increase the risk of progression and metastasis in transitional cell carcinoma of the bladder.

Carcinoma, Transitional Cell↗
PubMed1999

Staging of prostate cancer using 3-dimensional transrectal ultrasound images: a pilot study.

PURPOSE: We used conventional transrectal ultrasound images for 3-dimensional (D) reconstruction of the prostate, and determined its value in staging clinically localized prostate cancer. MATERIALS AND METHODS: A total of 36 patients with newly diagnosed clinically localized prostate cancer were studied. All patients underwent conventional transrectal ultrasonography with 3-D reconstruction. Images were examined and analyzed blindly, and findings were compared to histopathological staging following radical prostatectomy. RESULTS: Pathological staging of specimens revealed 15 sites of extracapsular extension in 10 patients, of whom 8 had positive margins and 2 had seminal vesicle invasion. The 3-D imaging identified 12 sites of extracapsular extension in 9 patients with 80% sensitivity, 96% specificity and 90% positive predictive value. Of the 2 patients with seminal vesicle invasion 1 was identified correctly on 3-D images. Overall staging accuracy of 3-D imaging was 94%. CONCLUSIONS: The 3-D reconstruction of conventional transrectal ultrasonography imaging is superior to 2-D imaging for staging localized prostate cancer. However, this advantage relies entirely on the visibility of prostate cancer lesions on conventional ultrasonography. Further studies are warranted to evaluate this technology for the management of prostate cancer.

Aged↗
PubMed1998

Expression of Bcl-2, Bax, and p53 in high-grade prostatic intraepithelial neoplasia and localized prostate cancer: relationship with apoptosis and proliferation.

BACKGROUND: Apoptosis-regulating genes have been shown to be important in the biology of prostate cancer. The aim of this study was to examine and correlate the expression of the apoptosis-regulating genes bcl-2, bax, and p53 with the frequency of apoptosis and rate of proliferation in benign prostatic epithelium (BP), prostate cancer, and high-grade prostatic intraepithelial neoplasia (HGPIN), which is currently considered the most likely precursor of prostate cancer. METHODS: Forty-four patients with histologically proven prostate cancer were investigated. All the men underwent radical prostatectomy. Immunohistochemistry was performed to assess expression of bcl-2, bax, and p53, and proliferation rate, as measured by the Ki-67 index. The frequency of apoptotic bodies was assessed by morphological criteria. RESULTS: The apoptotic index (AI) was highest in prostate cancer, and was significantly greater in HGPIN compared to benign prostate. The Ki-67 index was greatest in cancer, intermediate in HGPIN, and lowest in BP. The AI was increased in areas of BP in patients treated with neoadjuvant androgen ablation. No change in AI was seen in treated cases of HGPIN or cancer. Accumulation of p53 protein was infrequent in prostate cancer (2/43: 4.6%), and was absent in HGPIN. Bcl-2 overexpression was present in 2.3% of cancers (1/43) and in 34.9% of cases of HGPIN (15/43). Bax expression was seen in all cases of cancer and HGPIN. There was no correlation between bcl-2 expression and the apoptotic and Ki-67 indices in HGPIN. CONCLUSIONS: p53 and bcl-2 expression is infrequent in clinically organ confined prostate cancer. Bcl-2 expression is significantly higher in HGPIN than in both the associated prostate cancer and BP. The AI and Ki-67 index appeared intermediate in the putative precursor lesion HGPIN compared to prostate cancer and BP.

Androgens↗