Search PubMed⌕ Search

Biomedical subjects

R A Persad

Publications and source records attributed to R A Persad.

At least 37 records · Page 2Linked to original sources

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↗

Surgical management of the renal manifestations of von Hippel-Lindau disease: a review of a United Kingdom case series.

OBJECTIVE: To review the results of nephron-sparing surgery in a group of patients with von Hippel-Lindau (VHL) disease, a rare familial cancer syndrome which is dominantly inherited and predisposes affected individuals to developing various tumours, including haemangioblastomas of the retina and central nervous system, and multicentric renal cell carcinoma (RCC). PATIENTS AND METHODS: The 11 patients (seven men and four women, age range 27-62 years) assessed had been referred for surveillance to the Department of Clinical Genetics, Addenbrooke's Hospital, often having presented with neurological or ocular manifestations of the disease. Their case notes were reviewed to assess the results of conservative surgery. Five patients had more than one parenchymal-sparing operation (either partial nephrectomy or enucleation, i.e. removal of a malignant lesion with a 0.5 cm rim of normal tissue) while four had bilateral procedures. At the time of surgery, co-existent cysts were aspirated to allow a more accurate definition on computed tomography during follow-up. RESULTS: At a mean follow-up of 60 months after surgery, eight patients were alive with good renal function. Three patients were alive with paraplegia or paraparesis from spinal cord lesions. The three patients who died (aged 50, 40 and 31 years) were diagnosed when RCC was already advanced and renal tissue-preserving surgery was not possible. CONCLUSIONS: Nephron-sparing surgery may be justified because morbidity is reduced in patients whose quality of life may already be compromised by neurological and other problems, and because the lesions of RCC are often small, enucleation may also be justifiable in the attempt to conserve renal tissue and delay disease progression.

Adult↗

A review of antegrade stenting in the management of the obstructed kidney.

OBJECTIVE: To review experience in the management of the obstructed ureter using antegrade stenting in a variety of conditions. PATIENTS AND METHODS: Between 1984 and 1993, 41 patients (mean age 57 years, range 9-83) had antegrade stents placed by an experienced interventional radiologist. The causes of obstruction were urological in 27, gynaecological in eight, colorectal in three and miscellaneous in three. RESULTS: The overall success rate for antegrade stent insertion was 83% and the failure rate was greatest (four of six) in cases of ureteric injury following gynaecological procedures. There were no immediate complications. CONCLUSION: Antegrade stenting can be used as a temporary or permanent solution to ureteric obstruction. The technique is safe, acceptable to patients and avoids the need for a general anaesthetic.

Adolescent↗

Clonal analysis of human recurrent superficial bladder cancer by immunohistochemistry of P53 and retinoblastoma proteins.

PURPOSE: To investigate the clonal origin of malignant cells in recurrent superficial bladder cancer. MATERIALS AND METHODS: We compared the protein expression of p53 and retinoblastoma (Rb) by immunohistochemistry using antibody P1801 and PMG3-245, respectively, in 13 patients at the time of primary superficial bladder cancer resection (6 Ta and 7 T1) and their 15 corresponding recurrences of disease. Mutations in p53 and Rb were inferred on the basis of immunoperoxidase staining. RESULTS: At the time of initial tumor resection, a p53 mutation was observed in 5 patients (39%) and an Rb mutation was observed in 3 (23%). The p53/Rb mutation status of recurrent bladder cancers completely matched their corresponding primary bladder cancer. CONCLUSIONS: The chance that recurrent bladder cancer originated from independent clones in this study was extremely small (p < 10(-6)). This result strongly supports the monoclonal origin of recurrent superficial bladder cancer.

Carcinoma, Transitional Cell↗

An immunohistochemical and prognostic evaluation of cathepsin D expression in 105 bladder carcinomas.

Cathepsin D is a widely expressed aspartyl lysosomal protease. Clinical studies in several tumor types have shown a strong correlation between cathepsin D expression and tumor progression. In breast carcinoma, its expression is an independent prognostic factor associated with an increased risk of death. However, there have been no studies evaluating cathepsin D in bladder tumors. Therefore, the aim of this study was to determine the pattern of expression of cathepsin D in a large series of bladder carcinomas and assess its role as a prognostic factor against established variables. The tumors from 105 patients (median age 73) (median follow-up 26 months) with transitional cell carcinoma of bladder were examined. Forty-nine patients had superficial tumors (16 pTa; 33 pT1), 56 had invasive tumors (14 pT2; 42 pT3); there were 35 grade 1/2 tumors and 70 grade 3 tumors. These were stained by a standard immunohistochemical technique with an anti-cathepsin D monoclonal antibody. All 4 normal bladder specimens were positive for cathepsin D. Fifty-four tumors (51%) were positive for cathepsin D and 51 (49%) were negative. Chi square analysis showed a significant positive relationship between negative cathepsin D expression and stage (p < 0.0005), grade (p < 0.0001) and tumor morphology (p = 0.001). There was no relationship between cathepsin D expression and tumor ploidy (p > 0.1) or patient age (p = 0.09). Univariate analysis of disease-free and overall survival showed that negative cathepsin D expression (p = 0.01 and p = 0.0003 respectively), stage (p = 0.004 and p < 0.005 respectively) and grade (p = 0.02 and p = 0.0007 respectively) were associated with significantly worse prognosis. However, in a multivariate analysis of age, stage, grade and cathepsin D expression, only stage remained significant for overall survival (p < 0.005). The observed result for cathepsin D in the univariate analysis is probably due to its strong association with grade and stage. Nevertheless, cathepsin D status was able to provide additional prognostic information for overall survival in invasive tumors when stratifying for grade (p = 0.047), which suggests that it might provide additional prognostic data within particular tumor stages.

Adult↗

Quantification of angiogenesis as an independent predictor of prognosis in invasive bladder carcinomas.

OBJECTIVE: To evaluate angiogenesis as a prognostic marker of transitional cell carcinoma of the bladder and to assess its relationship to established variables for survival. MATERIALS AND METHODS: Forty-five tumours (two G2T2, seven G3T2 and 36 G3T3) from 36 men and nine women with a mean age of 73 years (range 50-91), who had been followed-up for a median of 37 months (range 1-50), were examined. Vessels were immunohistochemically highlighted using an antibody to the platelet endothelial cell adhesion molecule, CD31. Microvessel density was quantified using a Chalkley point eyepiece graticule. RESULTS: Univariate analysis of survival showed stage, grade and vascular count were significant indicators of prognosis (P = 0.002, P = 0.007, P = 0.019 respectively). No relationship was observed between stage and grade and vascular count. In a Cox proportional hazard model, adjusted for age and stage, microvessel density not only remained a significant prognostic indicator (P = 0.026) but was as informative as stage in predicting overall survival. A high vascular count conferred a 2.5 increased risk of mortality. CONCLUSIONS: These findings suggest that assessment of angiogenesis by microvessel quantification is an independent predictor of survival in patients with invasive bladder carcinoma and might be useful in selecting those who would benefit from adjuvant therapy.

Aged↗

Prognostic value of c-erbB-2 and epidermal growth factor receptor in stage A1 (T1a) prostatic adenocarcinoma.

OBJECTIVE: To determine whether the presence or absence of the oncoproteins epidermal growth factor receptor (EGFR) and c-erbB-2 could predict tumour behaviour. PATIENTS AND METHODS: Tissue from 45 stage A1 (T1a) prostatic adenocarcinomas from patients with a mean age of 65 years were immunostained for EGFR (12E) and c-erbB-2 (NCL-CB11). Their expression in the tumour and surrounding benign hyperplastic epithelium was correlated with each other and with survival. RESULTS: Forty percent (18 of 45) and 36% (16 of 45) of patients respectively were EGFR and c-erbB-2 positive in the tumour. Expression of these tyrosine kinase oncogenes was not confined to the tumour and the surrounding hyperplastic prostate was also positive for EGFR in 76% (34/45) of patients and for c-erbB-2 in 16% (11 of 45). EGFR and c-erbB-2 expression was weakly associated in both benign and malignant epithelium. Statistical analysis of survival showed that tumour c-erbB-2 expression was associated with a significantly worse prognosis (exact two tailed P = 0.0316), whereas no significant association was observed between EGFR expression and survival (P = 0.737). CONCLUSION: As c-erbB-2 expression increases the rate of dying by 4.2 times, recording its expression by these tumours may be useful in selecting patients who would benefit from treatment in stage A1 (T1a) disease.

Adenocarcinoma↗

p53 and c-myc expression in stage A1 prostatic adenocarcinoma: useful prognostic determinants?

Forty-five stage A1 prostatic adenocarcinomas from patients with a mean age of 65 years were examined for p53 and c-myc expression to determine whether the presence or absence of these proteins could predict tumor behavior. Thirteen (6 of 45) and seventy-three percent (33 of 45) of cases were respectively p53 and c-myc positive. p53 expression was confirmed to the tumor cells, whereas c-myc immunoreactivity was present in both malignant and surrounding hyperplastic prostate. Statistical analysis showed that although p53 and c-myc expression were positively correlated, expression of neither nuclear protein was associated with a significantly worse survival (p53: p = 0.0791 exact two-tailed; c-myc: p = 0.738 exact two-tailed). These results suggest that while both p53 and c-myc may play a role in prostatic carcinogenesis, neither appears to identify patients who may benefit from treatment in stage A disease.

Adenocarcinoma↗

Intravesical foreign bodies: five-year review.

All manner of foreign bodies have been extracted from the bladder. Introduction into the bladder may be through self-insertion, iatrogenic means or migration from adjacent organs. Extraction should be tailored according to the nature of the foreign body and should minimise bladder and urethral trauma. Complete extraction should also be confirmed by panendoscopy at the end of the extraction procedure. A 5-year review of our experience in this field has been conducted and the management and complications of intravesical foreign bodies are described. Of the 15 patients presenting to this department, 11 presented acutely and 4 presented with chronic symptoms due to complications which arose later. The possibility of an intravesical foreign body should be considered in any patient with chronic unexplained lower urinary tract symptoms.

Adult↗

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↗

Urological audit: the role for an aggressive approach to high grade superficial bladder tumours.

A retrospective study was undertaken of the different treatment modalities for bladder tumours under the care of 3 consultants in the urology department of a district general hospital. The aim was to review the results of the various forms of treatment. In all, 261 patients' case records were reviewed and 19 variables extracted. There was an average delay of 4.2 months from the onset of symptoms to the initial cystoscopy. Over 50% of high grade tumours were invasive on initial presentation (G3T2/G3T3). A range of treatments for the more aggressive tumours was adopted by the urologists, ranging from a conservative resection (TURBT) to an aggressive approach (cystourethrectomy) at the earliest sign of progression. A strong association between aggressive treatment and higher survival was noted. This study has proved valuable in demonstrating to the urology team the value of routine audit and questioning "established" surgical practice. As a result, a more standard regime for the treatment of bladder tumours has been advocated and a prospective randomised controlled trial will be introduced.

Adult↗

A departmental audit of patients with bladder cancer.

In keeping with the recent demands of the Department of Health for medical audit in clinical practice, an audit was undertaken of the management of bladder cancer patients in a large department of urology having three consultants with varied approaches of management. This study revealed interesting controversial areas for further scrutiny. For example, the poor prognosis of grade 3 T1 tumours with and without associated carcinoma-in-situ (CIS) and the speed of progression to invasive disease have indicated that a change to a more aggressive approach to the management of these tumours is necessary. High recurrence rates at the site of the original tumour (60%) and the presence of CIS also indicate the need for expert and thorough initial tumour assessment. The delays in diagnosis and treatment lend further support to the need for a 'haematuria clinic' to minimise such delays, which may influence prognosis. To reduce the occurrence of systematic errors in the recording, follow-up and surveillance of patients with bladder cancer, a protocol is suggested for a structured approach to optimise results, particularly in the poor prognostic categories.

Adult↗

Magnetic resonance imaging in the staging of renal cell carcinoma.

A prospective study has been carried out to examine the role of magnetic resonance imaging (MRI) in the investigation of renal cell carcinoma in 24 patients. In all cases the inferior vena cava (IVC) was well demonstrated with MRI. In 14 out of 15 patients where surgical correlation was available, the MRI and operative staging were in agreement. Magnetic resonance imaging and computed tomographic (CT) staging were in agreement in 16 out of the 17 patients where both were performed. In one case, CT suggested hepatic invasion but this was found not to be present on MRI and at operation. Magnetic resonance imaging also provided substantial additional information in three patients, including two cases where MRI demonstrated a patent IVC that appeared occluded on CT (one of which also had vertebral metastases seen on MRI but missed on CT) and one case where CT failed to demonstrate minimal involvement of the IVC. Magnetic resonance imaging is an accurate means of staging renal cell carcinoma with clear advantages over CT. In no case in this series was inferior vena cavography found to be necessary.

Carcinoma, Renal Cell↗