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D A Gillatt

Publications and source records attributed to D A Gillatt.

At least 37 records · Page 2Linked to original sources
PubMed1999

Pharmacodynamics of a long acting depot preparation of avorelin in patients with prostate cancer. Avorelin Study Group.

PURPOSE: We evaluate the pharmacodynamics, pharmacokinetics and tolerability of a sustained release depot formulation of avorelin, a new potent super agonist of luteinizing hormone-releasing hormone receptors, in patients with prostate cancer. MATERIALS AND METHODS: A total of 60 patients were randomized to receive a 10 mg. (31) or 15 mg. (29) avorelin subcutaneous depot. Serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and plasma avorelin were measured regularly until depot exhaustion. RESULTS: Of the 10 mg. group patients 3 withdrew from the study after 31 to 35 weeks due to disease progression. Of the 15 mg. group patients 1 did not complete the study for logistical reasons. After the expected flare in serum testosterone, LH and FSH during week 1, medical castration (testosterone concentration less than 1.735 nmol./l.) was achieved within 4 weeks of depot injection. Median duration of testosterone suppression was 40 weeks in the 10 mg. (95% confidence interval 35 to 42) and 39 in the 15 mg. (37 to 43) group. The reduction in serum LH was similar to that of testosterone, while that of FSH was less pronounced. Plasma avorelin was proportional to the dose and correlated with serum testosterone. Normalization of serum prostate specific (4 ng./ml. or less) at 6 months was achieved in 80 and 88% of the 10 and 15 mg. groups, respectively. During the (7 to 20-month) observation period 94 and 86% of the 10 and 15 mg. groups, respectively, complained of adverse events mainly related to androgen suppression (hot flushes, decreased libido and impotence) or the nature of the disease (skeletal pain). In each group 3 patients had serious adverse events requiring hospitalization for reasons unrelated to avorelin treatment. The depot was well tolerated locally. CONCLUSIONS: Subcutaneous depot formulations of avorelin were well tolerated and had protracted inhibitory effects on pituitary gonadotropin secretion in patients with prostate cancer. Testosterone suppression was maintained for more than 6 months in all patients. Avorelin depots could be the first luteinizing hormone-releasing hormone agonist formulation to be administered at 6-month intervals.

Adult↗
PubMed1999

Preoperative p53, bcl-2, CD44 and E-cadherin immunohistochemistry as predictors of biochemical relapse after radical prostatectomy.

PURPOSE: Since radical prostatectomy is performed to cure prostate cancer, identification of markers enabling preoperative prediction of relapse after radical prostatectomy is essential to counsel and select patients for adjuvant therapy. Aberrant p53, bcl-2, CD44 and E-cadherin immunohistochemistry has been associated with aggressiveness in prostate cancer. We assessed these biomarkers in biopsy and radical prostatectomy specimens as predictors of biochemical relapse. MATERIALS AND METHODS: A total of 76 patients with untreated clinically localized prostatic adenocarcinoma underwent radical prostatectomy. Preoperative (prostate specific antigen, biopsy Gleason score) and postoperative (pathological stage and margin status) variables, biopsy and radical prostatectomy biomarker immunohistochemistry were correlated with relapse. Univariate and multivariate statistical analyses identified significant predictors. RESULTS: Of the 76 patients 23 (30%) had relapse (mean followup 38 months). Aberrant p53, bcl-2, CD44 and E-cadherin expression was observed in 64, 12, 85 and 12% of biopsies and 57, 20, 64 and 49% of radical prostatectomy specimens, respectively. Biopsy Gleason 7 to 10 and biopsy p53, respectively, gave the highest positive and negative predictive values for relapse. Relapse occurred in 13% of patients with normal biopsy p53 and in half with aberrant p53. Multivariate analysis revealed Gleason score and p53 to be independent preoperative predictors (p = 0.01 and 0.02, respectively). Estimated risk of relapse was 3.5 times higher in patients with Gleason scores 7 to 10 and 24% higher in those with aberrant p53. Significant postoperative predictors were bcl-2, p53, Gleason score and margin status (p = 0.01, 0.01, 0.04 and 0.01, respectively). CONCLUSIONS: Aberrant biopsy p53 is associated with a significantly worse outcome after radical prostatectomy than normal p53, highlighting a potential clinical role for p53. Postoperative p53 and bcl-2 were significant predictors of outcome after radical prostatectomy.

Aged↗
PubMed1998

Ductal carcinomas of the prostate: a clinicopathological and immunohistochemical study.

OBJECTIVES: To confirm the expression of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) in ductal carcinomas of the prostate, and to analyse p53, Ki67, oestrogen (ER) and androgen (AR) receptors in these tumours. MATERIALS AND METHODS: Paraffin-embedded samples from 12 patients with ductal carcinoma of the prostate were assessed for pattern, mitotic count and the presence of a microacinar carcinoma component. There were six pure ductal and six mixed microacinar and ductal carcinomas. Sections were stained immunohistochemically for the expression of PSA, PAP, Ki67, p53, AR and ER. Clinical data were obtained from case notes. RESULTS: Six of the ductal tumours had a papillary pattern whilst the others had a cribriform appearance. The mitotic rates in the ductal areas were high in the tumours from eight of the 12 patients. PSA and PAP immunohistochemistry were positive in all the cases. No ER immunoreactivity was found in any of the patients. Ten of the ductal tumours showed strong reactivity with AR, the other two were weakly positive; two of the tumours were strongly positive for p53 protein. All the ductal carcinomas expressed Ki67, three having > 25% nuclear marking. One patient who was strongly positive for p53 and had a high Ki67 score survived only one year after diagnosis. Survival ranged from 1 to 13 years after diagnosis. CONCLUSION: This study confirms the expression of PSA and PAP in ductal carcinomas of the prostate. The percentage of tumours expressing p53 was similar to that published for high-grade microacinar carcinomas. The results for Ki67 suggest that ductal tumours have higher scores than microacinar tumours, but further studies are required to ascertain if this is significantly different. As half the patients with ductal tumours had co-existent microacinar tumours, we advise transrectal prostatic biopsies in patients diagnosed with pure ductal carcinomas on transurethral resection specimens, to exclude high-grade microacinar carcinomas. The presence of AR and the lack of ER in all the ductal carcinomas confirms that these tumours are prostatic in origin and should be treated with antiandrogen therapy.

Acid Phosphatase↗
PubMed1998

Epidemiology of transitional cell carcinoma of the bladder: profile of an urban population in the south-west of England.

OBJECTIVES: To produce an epidemiological profile of patients with transitional cell carcinoma (TCC) of the bladder living in the city of Bristol (south-west England), to determine if TCC tumorigenesis is linked to possible risk factors (occupational exposure, cigarette smoking, alcohol consumption and coffee consumption) and to assess phenotypic acetylation status and thus determine whether there may be a genetic component to tumour development. PATIENTS AND METHODS: This cross-sectional observational epidemiological study recruited both cases and controls from one-stop haematuria clinics, providing two groups with a similar age and sex distribution. Before diagnosis, all patients were interviewed by the same researcher and results recorded on a specially designed database questionnaire, to eliminate both recall and investigator bias. Metabolic studies were also performed before diagnosis. RESULTS: There were significant associations for occupational exposure, cigarette smoking, and beer consumption (but not wine or spirits), but no significant association with coffee consumption. Slow acetylation status also conferred an increased risk. There were linear trends in terms of dose-response for both beer and cigarette consumption, although this was significant only for cigarettes. There was no difference in risk between the use of filtered or unfiltered cigarettes. CONCLUSION: Occupational exposure and cigarette smoking have been well documented as risk factors in the development of TCC of the bladder, as has slow acetylation status. There are very few studies linking bladder cancer with alcohol consumption. It is important to subdivide types of alcohol consumed when considering this factor in an epidemiological study. In the case of beer, methods used by different brewing processes may also contribute to differences found, were such a study to be performed on a national scale.

Acetylation↗
PubMed1998

Prevalence and impact of incontinence and impotence following total prostatectomy assessed anonymously by the ICS-male questionnaire.

OBJECTIVES: The aim of this study was to assess the incidence of incontinence and impotence in patients following total prostatectomy and assess the impact their symptoms have on their quality of life. PATIENTS AND METHODS: Between 1987 and 1994, one surgeon performed retropubic total prostatectomies on 89 patients, of which 87 were available for follow-up. All patients were sent an ICS-male questionnaire. Patients' ages ranged from 49 to 73 years (median 65). The interval between surgery and completing the questionnaire ranged from 7 to 87 months (median 22). RESULTS: The response rate was 95%. No patients reported incontinence pre-operatively. Postoperatively, 69% (57/83) of patients suffered to some degree of leakage of urine and 24% (29/83) used pads. Of these, 60% used 1 pad per day, 15% 2 pads and 25% (5 patients) used 3 or more. Nocturnal incontinence was reported by 20% of patients. Urinary incontinence was considered a problem in only 34% (28/83) of patients. Sixty-five percent of patients using pads considered urinary leakage to be a problem, but only 1 considered it a serious problem. 89% claimed to have been potent prior to surgery. The overall postoperative potency rate was 41% (30/74) in those potent pre-operatively. However, 67% of patients reporting potency had severely reduced rigidity, and only 12% (9/74) achieved what they considered full erections. Ten percent of all patients considered postoperative impotence to be a serious problem, and 47% stated that it was not a problem at all. CONCLUSIONS: The incidence of incontinence and impotence following total prostatectomy is higher than earlier reports suggest, but the impact of these complications appears to be surprisingly low. These results allow patients to be given realistic expectations when counselled prior to this operation.

Aged↗
PubMed1997

A comparison of endorectal magnetic resonance imaging and transrectal ultrasonography in the local staging of prostate cancer with histopathological correlation.

OBJECTIVE: To assess the staging accuracy of endorectal magnetic resonance imaging (MRI), using a mid-field system, in patients with clinically localized prostate cancer and to compare the results with transrectal ultrasonography (TRUS). PATIENTS AND METHODS: Twenty patients with clinically localized prostate cancer were prospectively staged with TRUS and endorectal MRI using a 0.5 T magnet. All patients subsequently underwent radical prostatectomy and the results of pre-operative staging were compared with the histological findings. RESULTS: The sensitivity and specificity for diagnosing capsular penetration were 38% and 100%, respectively, for endorectal MRI, and 23% and 86% for TRUS. The sensitivity and specificity for diagnosing seminal vesicle invasion were 100% and 94%, respectively, for endorectal MRI, and 33% and 100% for TRUS. The overall staging accuracy for endorectal MRI was 75% compared with 50% for TRUS. CONCLUSION: Compared with TRUS, endorectal MRI with a 0.5 T magnet provided greater sensitivity and specificity for capsular penetration and increased sensitivity for seminal vesicle invasion.

Aged↗
PubMed1996

Endorectal MRI using a 0.5 T mid-field system in the staging of localized prostate cancer.

The accuracy of high field, endorectal MRI in the staging of localized prostate cancer has been the focus of many previous reports. We present our findings with a mid-field magnet. Twenty-two patients with clinically localized prostate cancer were prospectively staged with endorectal MRI using a 0.5 T magnet. All patients subsequently underwent radical prostatectomy and the results of pre-operative MRI staging were compared with the histological findings. The overall staging accuracy for mid-field, endorectal MRI was 77% (17/22). The sensitivity and specificity were 50% (7/14) and 100% (8/8), for diagnosing capsular penetration and 100% (4/4) and 94% (17/18), for seminal vesicle invasion. This study demonstrates that as a result of recent developments in mid-field MRI design it is now possible to use these MR systems in conjunction with an endorectal probe to stage localized prostate cancer and that the accuracy is comparable to previous reports using high-field magnets.

Humans↗
PubMed1996

A review of radical prostatectomy from three centres in the UK: clinical presentation and outcome.

OBJECTIVE: To examine critically the clinical presentation, pathological stage and outcome in patients selected for radical prostatectomy combining data from three centres where the operation has been carried out routinely for more than 5 years. Comparisons were made between impalpable tumours presenting at transurethral resection of the prostate (TURP) for clinically benign disease, tumours diagnosed at needle biopsy performed because the serum prostate-specific antigen (PSA) was elevated, and palpable, clinically localized cancer detected by digital rectal examination (DRE). PATIENTS AND METHODS: Clinical and pathological findings recorded in the hospital notes of 183 patients who had undergone exploration for radical prostatectomy at St Bartholomew's Hospital, London, Southmead Hospital, Bristol, and the Royal Infirmary, Stirling, between 1987 and 1994 were transcribed onto a proforma and analysed. Patients were categorized by clinical stage and the relationships between clinical presentation, serum PSA level, pathological stage, tumour grade and outcome were examined. RESULTS: The pathological extent of clinically unsuspected cancer identified at TURP was highly variable. Well-differentiated tumours occupying < 5% of the TURP specimen were generally found to be less extensive at subsequent radical prostatectomy than either impalpable malignancy diagnosed by needle biopsy performed because PSA levels were raised or palpable tumours associated with a unilateral abnormality on DRE. Unsuspected tumours diagnosed at TURP that were less than well differentiated or occupied > 5% of the surgical specimen were more commonly associated with extra-prostatic invasion or metastatic disease than were tumours detected by raised PSA levels or an abnormal DRE. Serum PSA did not reliably predict either clinical stage or pathological extent, but no patient with nodal metastases had a PSA level of < 12 ng/mL. Similarly, pathological stage could not be predicted confidently from the whole-tumour grade ascertained after surgery. The extent of malignancy in patients referred because of lower urinary tract symptoms was not significantly different from that among patients referred specifically because the PSA level was raised or the DRE was abnormal. However, there was a trend for patients found to have cancer in specific screening programmes to have a malignancy that was less extensive and therefore more frequently confined to the gland than in those not identified by screening. CONCLUSION: Among patients with unsuspected malignancy diagnosed at TURP, those with well differentiated tumours in < 5% of the specimen had significantly less advanced disease than men found to have less differentiated or more extensive malignancy in the resected specimen. Impalpable cancer associated with a raised PSA level diagnosed by needle biopsy represented an intermediate group comparable to those with unilateral palpable malignancy. This suggests that needle biopsies may be worthwhile in some patients with an apparently benign prostate and raised PSA level with a view to identifying clinically significant but potentially curable cancer. Screening may detect less extensive tumours, but the natural history of these cancers is unknown and observed survival will be subject to lead-time and length bias when compared to symptomatic disease. Prospective randomized studies of both screening and treatment modalities, including surgery and radiotherapy, are required to define the impact of radical prostatectomy on disease-specific survival in men with early stage prostate cancer.

Adult↗
PubMed1996

Recurrent transitional cell carcinoma arising within an ileal conduit following cystectomy. A case report and review of the literature.

Recurrent transitional cell carcinoma arising within an ileal conduit following cystectomy for malignant disease is rare. We report on a case in which such a recurrence occurred, well away from the ureteroileal anastomosis and without coexisting upper tract involvement. The possible pathogenesis of these recurrences is discussed and the existing literature reviewed. Although uncommon, the possibility of recurrence within a conduit should be considered in any patient who presents with haematuria following a resection for malignant disease.

Aged↗
PubMed1993

Lipoprotein levels following treatment with cyproterone acetate or LHRH analogues.

Fasting serum lipoproteins were measured in patients with carcinoma of the prostate. Twelve patients were on no hormonal treatment (Group 1). Fifteen were on cyproterone acetate (Group 3), 17 were on the long-acting LHRH analogue Zoladex (Group 4) and 11 on a combination of cyproterone acetate and Zoladex (group 5). In addition, 27 patients with benign urological disease were taken as controls (Group 2). In both groups in which cyproterone acetate was part of the treatment the total high density lipoprotein cholesterol levels were significantly lower than in the other groups. Patients on cyproterone acetate alone had significantly higher levels of very low density lipoprotein (VLDL) triglyceride levels than those not on cyproterone acetate. These results confirm changes in serum lipoprotein levels in patients taking cyproterone acetate and these changes may have potential adverse effects if the treatment is prolonged.

Cholesterol↗
PubMed1992

Dialysis in patients with upper urinary tract transitional cell carcinoma.

In some patients with primary malignant disease of the kidney the only way of achieving a cure may involve radical surgery. If the tumour is bilateral or involves a solitary kidney, renal failure may be unavoidable. The role of dialysis and transplantation in these patients following "curative" cancer surgery is not clear. A review of the literature and experience with 4 patients who ultimately had bilateral nephrectomies for multiple recurrent upper tract urothelial malignancy is reported. These 4 patients remained free of tumour recurrence on dialysis at 5, 8, 12 and 72 months respectively since commencing dialysis, although 2 have died from unrelated causes. It would seem reasonable to offer dialysis followed by subsequent transplantation in this group of patients after a period of 1 to 2 years has elapsed without any evidence of malignant recurrence.

Adult↗