Reversible hypertension in a young female: ureteric obstruction due to endometriosis.

We present the case of a young female who, upon investigation for hypertension, was found to have a ureteric stricture secondary to endometriosis. After excision of the stricture and an end-to-end ureteric anastomosis the patient's blood pressure returned to normal. This case highlights the need to investigate fully hypertension in young people and to consider the possibility of endometriosis in any female who presents with obstructive uropathy.

Investigation of upper tracts after resolution of symptoms due to ureteric calculi.

OBJECTIVE: To determine whether patients with proven ureteric calculi on IVU require repeat IVU after resolution of symptoms and passage of calculus on plain X-ray. METHODOLOGY: IVU reports for a 12-month period were obtained and notes and X-rays of those patients with ureteric calculi were reviewed. Presentation, management and subsequent imaging after resolution of symptoms were determined for each patient. All X-rays were reviewed by a uroradiologist. RESULTS: Fifty-eight patients were investigated for the study. All initial IVUs showed upper tract dilation or obstruction. Forty-three eventually passed their calculi spontaneously and of these, 18 had KUB, all of which showed passage of the calculus and 25 had repeat IVU, 22 of which were normal. The 3 abnormal IVUs showed persisting calculi which were visible on the plain film. Fifteen patients required surgical intervention and all had repeat IVU, of which 5 were abnormal. CONCLUSION: This study suggests that following resolution of symptoms due to ureteric colic, patients who pass their calculi spontaneously can be followed up by KUB. Only those with persistent calculi on KUB or those who have had surgical intervention require repeat IVU.

A 7-year audit in a single centre of the results of the modified template retroperitoneal lymph node dissection for testicular teratoma.

OBJECTIVE: To audit the results of retroperitoneal lymph node dissection (RPLND) after chemotherapy for testicular nonseminomatous germ cell tumour (NSGCT) in a single centre over a 7-year period, using a modified template technique via a midline transabdominal approach. PATIENTS AND METHODS: Outcome data were collected prospectively on all patients undergoing RPLND for a residual retroperitoneal mass after chemotherapy for NSGCT between October 1990 and March 1998; 28 patients underwent 32 RPLNDs over this period. RESULTS: The clinical stage at presentation was stage I in three patients (12%), stage II in 15 (54%), stage III in one (4%) and stage IV in nine (32%). The histological classification included malignant teratoma differentiated in one patient, malignant teratoma intermediate in 12 (43%) and malignant teratoma undifferentiated in 12. Tumour markers were positive immediately before surgery in four patients. A midline transabdominal approach was used in 31 of the procedures. The size of the retroperitoneal tumour mass was <3 cm in four patients (13%), 4-8 cm in 16 (50%) and >9 cm in 12 (38%). Histology of the mass showed residual differentiated teratoma in 17 (53%), undifferentiated teratoma in six (19%), necrosis only in six (19%), adenocarcinoma in one and angiosarcomatous differentiation in two. There was no perioperative mortality. Eight patients had permanent loss of ejaculation (29%) and two had erectile dysfunction (7%). Five patients (20%) subsequently developed recurrent disease; three (12%) underwent reoperation for disease relapse (one requiring two further procedures), whilst two (8%) died from recurrent disease. CONCLUSION: An abdominal approach via a midline incision provides satisfactory access with minimal morbidity in most patients. Results comparable with larger series can be achieved in regional centres.

Developments in our understanding of detrusor instability.

It is important to recognize that our understanding of detrusor instability is far from complete. Although the significance of some of the abnormalities reported is unclear, it is likely that several factors will eventually be found to contribute to the overall clinical picture. Nevertheless, there is increasing evidence that the development of post-junctional supersensitivity of the detrusor muscle is implicated in each of the clinical subgroups of instability. Partial denervation of the detrusor appears to be the mechanism responsible for this in obstructive detrusor instability, but other abnormalities causing a chronic decrease in the excitatory motor innervation to the detrusor (e.g. decentralization, pre-synaptic inhibition) could produce similar effects and may therefore be involved. This evidence of a specific abnormality at the cellular level offers scope for therapy for detrusor instability with a new range of drugs, using agents that hyperpolarize the detrusor muscle membrane or modify calcium activation. However, bladder specificity remains a fundamental problem in the development of effective therapeutic agents for detrusor instability and poses the great challenge for the future.

A retrospective study of the investigation and management of muscle-invasive bladder cancer in the South West Region.

OBJECTIVE: To evaluate the present management of muscle-invasive bladder cancer in the South West Region and to assess the workload resulting from the rationalization of treatment in specific centres. METHODS: A retrospective survey was undertaken in all the hospitals in the South West Region, to assess the management of all patients presenting with muscle-invasive bladder cancer in the years 1989 and 1993. Data were collected from histopathology records and hospital in-patients' notes. The optimum standard of assessment and treatment were defined by a panel of specialists in urological tumours. The management of patients was compared against these defined standards. RESULTS: A total of 186 and 199 patients in 1989 and 1993, respectively, were evaluated. When comparing their assessment against the defined standard, only 69% of patients in 1989 and 58% in 1993 had an intravenous urogram, with 7% and 4%, respectively, having no upper tract imaging (the remainder undergoing ultrasonography). Evidence from an examination under anaesthetic (EUA) was found for 80% of patients in 1989 and 84% of patients in 1993. Only 23% of patients in 1989 and 36% in 1993 were staged by either computed tomography or magnetic resonance imaging. In both 1989 and 1993, 54% of patients had definitive treatment, 31% had an endoscopic follow-up only and 15% had no treatment; there were no differences in age or co-morbidity among these groups. The median time elapsed between referral and diagnosis was 59 days (1989) and 52 days (1993), and the median delay to definitive treatment was 114 and 96 days, respectively. CONCLUSION: There was insufficient upper tract imaging, poor clinical staging in the EUA and too few investigations for staging. The low rate of definitive treatment may be a consequence of the delays in management, allowing the tumour to progress, and suggesting the need for a more rapid assessment of haematuria.

Neuropathic urinary retention in the absence of neurological signs.

We present two cases of painless urinary retention secondary to central intervertebral disc prolapse. In neither case were there signs or symptoms suggesting an underlying neurological insult. Both patients voided spontaneously following neurosurgical intervention. The classical features of acute cauda equina compression may be absent in patients with central lumbar disc protrusion. Painless urinary retention may be the only physical sign.

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.

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.

Correlation of polymorphic expression of CYP2D6 mRNA in bladder mucosa and tumor tissue to in vivo debrisoquine hydroxylase activity.

Debrisoquine hydroxylase activity has been attributed to CYP2D6 and poor metabolizers of debrisoquine have a reduced relative risk of developing aggressive bladder cancer. Production of a proximate carcinogen could occur in liver or bladder mucosa. However, it is not known if CYP2D6 is expressed in human bladder mucosa. In vivo whole body debrisoquine hydroxylase activity was measured as the debrisoquine recovery ratio (DBRR) following single dose oral administration of debrisoquine (10 mg) in 10 normal subjects and 20 patients with bladder cancer prior to diagnostic cystoscopy. Semi-quantitative PCR was used to measure mRNA for CYP2D6 in bladder tissue obtained at cystoscopy. Of the 30 subjects, three were phenotypically and genotypically poor metabolizers. Among the extensive metabolizers, there were extensive intersubject variations in DBRR. A 10-fold variation in CYP2D6 mRNA levels was observed in bladder tissue. There was a highly significant association between DBRR and CYP2D6 mRNA expression (r2 = 0.702, P < 0.001). These results demonstrate the presence of CYP2D6 mRNA in bladder mucosa. Furthermore, they are consistent with debrisoquine hydroxylation being mediated by CYP2D6 and suggest that differences in mRNA concentration are rate limiting for enzyme activity and that bladder mucosal regulation reflects total body regulation for this enzyme. The expression of CYP2D6 in bladder mucosa suggests that this enzyme could be involved in the local production of a proximate carcinogen in this tissue and contribute to the pathogenesis of bladder cancer in man.

Current trends in the management of invasive bladder cancer.

In muscle-invasive bladder cancer, attempts at cure have traditionally involved radical local treatment by either radiotherapy or ablative surgery. However, these treatments have been associated with a high morbidity and have failed to address the problem of subsequent metastatic disease, to which many patients eventually succumb (often within the first 3 years after treatment). Modern imaging techniques have led to much improved staging information, allowing careful selection of patients suitable for radical "curative" treatment; at the same time, patients identified as already having metastatic disease may be spared major surgery that is unlikely to influence the outcome of their disease. Reconstructive surgical techniques are beginning to transform the quality of life for patients offered radical surgery, by avoiding the need for traditional urinary diversion. In addition, the use of neo-adjuvant chemotherapy combined with radical local treatment addresses the problem of micrometastases at diagnosis and offers the prospect of improved survival, although the results of clinical trials are awaited to evaluate this further. Future advances in treatment may be expected to occur as our understanding of the biology of bladder cancer increases. Of particular value will be predictive information about the invasive potential of initially superficial tumours, so that these cases may be targeted for "aggressive" treatment from the outset.

Current trends in the management of localised prostate cancer.

The incidence of prostate cancer in the UK is increasing, and the disease is being detected more often in younger patients (e.g. from routine PSA measurement during health-care screening). Left untreated, a significant proportion of patients will undergo progression of their disease locally and/or develop metastases. Modern imaging techniques have greatly aided the assessment of early prostatic cancer, enabling both accurate assessment of the primary tumour and giving valuable information regarding lymph node metastases. PSA measurements are also extremely helpful, and this has replaced acid phosphatase as a marker for prostatic malignancy. Controversy still remains, however, over the best form of management. Radical prostatectomy undoubtedly produces the best results in the literature, but the patients are highly selected (e.g. those with nodal metastases are excluded) and some patients with well differentiated tumours may have been over-treated, as they may have been expected to do well with surveillance alone. Full clinical trials are required in identically staged patients to assess the relative merits of surveillance, radiotherapy and surgery, and this should now be possible with recent advances in imaging techniques.

AIDS: the contamination risk in urological surgery.

Increasing numbers of patients infected with the Human Immunodeficiency Virus (HIV) will be encountered in surgical practice. The risk of exposure to the virus during urological surgery is unknown. In an attempt to quantify the risk and to identify procedures that require change, 427 consecutive urological operations were prospectively assessed for contamination of the surgeon's skin, face and mucous membranes by potentially infected body fluids. Contamination occurred in 136 procedures (32%), of which 37 of 123 (30%) were open operations and 99 of 304 (33%) were endoscopic. Contamination of the face and eyes accounted for 46% (46 of 99 operations) of the contamination occurring in endoscopic surgery. Attention must be paid to reducing exposure of the surgeons' skin to patients' body fluids. The surgeons' eyes should be protected by modification of urological techniques and equipment to avoid spillage.