Aberrant E-cadherin and alpha-catenin expression in prostate cancer: correlation with patient survival.

E-cadherin maintains the normal differentiated phenotype in epithelial cells; this function is partly mediated by alpha-catenin, which links E-cadherin to the cell cytoskeleton. Dysfunction of E-cadherin in vitro and in vivo is associated with an invasive phenotype. However, the role of alpha-catenin is largely undetermined. We analyzed the expression of E-cadherin and alpha-catenin in prostate cancer to assess the relationship of abnormal expression to stage, grade and survival. E-cadherin expression was evaluated in 99 prostate cancers. In 79 of those specimens, alpha-catenin was also assessed. In benign prostatic epithelium, both E-cadherin and alpha-catenin were expressed uniformly at the cell membrane. Abnormal E-cadherin expression was found in 56% of cancer specimens, whereas alpha-catenin expression was abnormal in 42%. Abnormal expression of each molecule was significantly correlated with Gleason score (P < 0.0001) and the ratio of resection chippings infiltrated by tumor (P < 0.0001). E-cadherin expression was also associated with the extent of disease on the initial bone scan (P = 0.017). Univariate analysis showed significantly lower survival rate for patients with abnormal E-cadherin (P = 0.0003) or alpha-catenin expression (P = 0.031). Multivariate regression analysis showed that the prognostic value of E-cadherin was independent of tumor grade but not of metastasis. These results suggest that perturbation of cell-cell adhesion is involved in the progression of prostate cancer and that analysis of E-cadherin expression may be clinically useful.

Evaluating the use of early hormonal therapy in patients with localised or locally advanced prostate cancer.

This article evaluates the use of early hormonal therapy in patients with localised or locally advanced prostate cancer. In patients receiving radiotherapy, an overall survival benefit is proven for adjuvant goserelin ('Zoladex') in locally advanced disease. Adjuvant to radical prostatectomy, castration (goserelin or orchiectomy) has demonstrated an overall survival benefit in patients with lymph node metastases. Survival advantages have not yet been proven with nonsteroidal antiandrogens, but immediate or adjuvant bicalutamide ('Casodex') improves objective progression-free survival in patients with locally advanced disease, with certain quality-of-life advantages over castration.

PSA recurrence following radical prostatectomy is comparable for all age groups in the UK.

UNLABELLED: Increasing numbers of men are being diagnosed with prostate cancer and undergo operative curative treatment. It has been suggested that outcome after radical prostatectomy (RP) may vary for different age groups. OBJECTIVE: To investigate whether PSA recurrence-free survival after RP is related to age at operation for a cohort of English men. METHODS: A total of 854 patients notes from four Urology units were audited for preoperative staging parameters and follow-up data obtained. The relationship of PSA, age, biopsy Gleason grade, clinical stage, era and institution on PSA recurrence-free survival was competitively assessed with a multivariate model. RESULTS: Only preoperative PSA (P<0.0001) and biopsy Gleason grade (P < 0.0001) were found to be strongly associated with PSA recurrence-free survival on multivariate analysis. PSA recurrence-free survival probabilities at 5 y for patients aged 45-55 y, 55.1-60 y, 60.1-65 y, 65.1-70 y and 70.1-75 y were 0.59 (CI 0.47-0.71), 0.74 (CI 0.64-0.784), 0.56 (CI 0.44-0.68), 0.61 (CI 0.53-0.69) and 0.60 (CI 0.46-0.74), respectively. No significant difference of PSA recurrence-free survival between any of the age groups was found (Log-rank, P = 0.8567). CONCLUSION: No significant difference of pathological variables or biochemical recurrence across the age groups was found. The widely held belief of poorer outcome in younger men selected for RP does not seem to be borne out by this study.

Discrimination by SZL49 between contractions evoked by noradrenaline in longitudinal and circular muscle of human vas deferens.

The effects of irreversible alpha1-adrenoceptor antagonists, SZL-49 (an alkylating analogue of prazosin), dibenamine and benextramine on contractions to noradrenaline (NA) in longitudinal and circular muscle of human epididymal vas deferens were investigated. Competitive alpha1-adrenoceptor antagonists were also used to further characterize the alpha1-adrenoceptor subtype stimulated by NA in longitudinal and circular muscle. NA evoked concentration-dependent contractions of both muscle types (pD2; 5.4 and 5.2 respectively). The contraction of circular muscle was comparatively more sensitive than that of longitudinal muscle to pretreatment with SZL-49. In contrast, dibenamine or benextramine produced comparable effects in both muscle types. The relationship between receptor occupancy and contraction in either longitudinal or circular muscle was nonlinear, with half-maximal response requiring similar receptor occupancy (longitudinal muscle 14%, circular muscle 16%). Maximal response in both muscle types occurred with little or no receptor reserve (<10%). The competitive alpha1-adrenoceptor antagonists produced dextral shifts of the dose-response curves to NA in longitudinal and circular muscle. The inhibitory potencies, estimated from the apparent pKB values were significantly different in longitudinal and circular muscle respectively for either WB 4101 (pKB, 8.6 and 9.5) or RS-17053 (pKB, 7.1 and 9.0) but not for Rec 15/2739 (pKB, 9.2 and 9.8) or HV 723 (pKB, 8.3 and 8.4). In conclusion, the potency profile of the competitive alpha1-adrenoceptor antagonists and the lack of different receptor reserves for NA in the muscle types suggest that the discriminatory effects of SZL-49 is primarily due to a predominance of the alpha1L-adrenoceptor subtype in longitudinal muscle and alpha1A-subtype in circular muscle.

Assessment of radiotherapy in invasive bladder carcinoma using in vivo methylene blue staining technique.

In vivo methylene blue staining of the bladder urothelium is a useful method as an adjunct to cystoscopy in detection of recurrent tumors or new ones after radical radiotherapy. The depth of staining correlates well with the grade of bladder tumor differentiation. It is a simple, safe, and acceptable procedure.

Postoperative care following internal urethrotomy.

A randomized prospective study was set up to assess the role of postoperative catheter drainage and the value of hydraulic self-dilatation of the urethra after internal urethrotomy. Sixty-two patients were admitted into the study and followed-up for two years. The results support the use of a no-catheter posturethrotomy management and advocate the encouragement of postoperative hydraulic self-urethral dilatation.

Spinal cord ischemia after ligation of both internal iliac arteries during radical cystoprostatectomy.

In radical cystectomy where control of the blood supply is desirable, ligation of both internal iliac arteries is to be avoided. The lumbar part of the spinal cord and cauda equina receive arterial radicular branches via the posterior trunks of the internal iliac arteries. Thus, bilateral ligation of these vessels might cause ischemia of the lower part of the spinal cord.

Casodex (bicalutamide) 150-mg monotherapy compared with castration in patients with previously untreated nonmetastatic prostate cancer: results from two multicenter randomized trials at a median follow-up of 4 years.

OBJECTIVES: To compare the efficacy, tolerability, and quality of life benefits of bicalutamide (Casodex) 150-mg/day monotherapy and castration in previously untreated nonmetastatic (M0) advanced prostate cancer. METHODS: A total of 480 patients with Stage T3/T4 nonmetastatic disease randomly received oral bicalutamide 150 mg/day or castration (either bilateral orchiectomy or goserelin acetate [Zoladex] 3.6 mg every 28 days) in a 2:1 ratio in two open multicenter studies (studies 306 and 307). The design of these studies was similar to allow a pooled analysis. RESULTS: In the combined survival analysis, at median follow-up of 202 and 205 weeks in studies 306 and 307, respectively, with 31% of the cases resulting in death, bicalutamide 150-mg monotherapy was statistically equivalent to castration; the risk of death from any cause was 7% less with bicalutamide than with castration (hazard ratio [HR] = 0.93). Data on time to treatment failure and objective progression could not be pooled, as results for these end points differed between the trials. In study 306, bicalutamide 150-mg monotherapy increased time to objective progression (HR = 0.58; P = 0.033) and treatment failure (HR = 0.66; P = 0.074), whereas in study 307, time to progression (HR = 1.35; P = 0.0471) and treatment failure (HR = 1.24; P = 0.097) favored castration. Bicalutamide therapy showed significant advantages over castration for both sexual interest (P = 0.029) and physical capacity (P = 0.046). Bicalutamide 150-mg monotherapy was well tolerated. CONCLUSIONS: Bicalutamide 150-mg monotherapy provides a similar survival outcome to castration in previously untreated patients with nonmetastatic advanced prostate cancer and confers statistically significant benefits over castration with respect to sexual interest and physical capacity.

Patient-Clinician choice in palliation of metastatic prostate cancer.

Palliation of patients with metastatic prostate cancer is based primarily on offering a form of androgen ablation. Each therapeutic modality has advantages and disadvantages. The decision with regards to the chosen option relies on thorough and open discussion between the treating urologist and the patient. Quality of life issues are increasingly an integral part of the treatment choice opted for. Thus, quality of life questionnaires should be incorporated into future clinical trial assessments and end-points.

Pure small cell carcinoma of the prostate.

Pure small cell carcinoma of the prostate is a rare anaplastic tumour. This report presents the clinicopathological findings of two patients presenting with this disease. Immunohistochemistry was positive for protein gene product 9.5, neurone specific enolase and calcitonin. Staining was negative for prostate specific antigen and prostate acid phosphatase. androgen ablation has no place in the management of this lesion and patients with this disease should be managed as if they have a neuroendocrine tumour.

Aetiological factors and management of priapism in Bristol 1978-1983.

Twenty-two patients with priapism presented in the Bristol clinical area during the period 1978-1983. Idiopathic priapism was present in eight patients only (36.4%) and identifiable causes were present in the remaining fourteen (63.6%). Fourteen various surgical shunts were carried out. Success of surgical treatment, as demonstrated by detumescence and maintenance of potency, was best achieved in those patients who were treated less than 12 hours following onset of priapism irrespective of whichever venous shunting technique was used (6 out of 7 patients--85.7%).

'Beehive on the bladder': a sign of colovesical fistula.

The 'beehive' sign on the bladder as seen in cystograms is valuable in diagnosing the presence of colovesical fistula and is invariably associated with the vesical end of the fistulous tract.

Angiomyolipoma of the kidney: a clinical enigma in diagnosis and management.

Renal angiomyolipomas are uncommon benign tumours which clinically mimic renal cell carcinoma. They have characteristic features on ultrasound and CT scanning which may enable their diagnosis preoperatively. We review our experience of six cases of renal angiomyolipoma. These cases highlight the difficulties in making a preoperative diagnosis despite the use of modern scanning. We advocate conservative resection when the diagnosis is made preoperatively and when technically possible, but radical nephrectomy should be performed if there is a possibility of a carcinoma.

Use of collagen implant for posterior rectopexy in complete rectal prolapse: preliminary communication.

A variety of materials has been used for perirectal implantation in the treatment of complete rectal prolapse. A new material (Zenoderm) prepared from porcine corium has been used successfully in 4 patients. The material proved to be inert, biologically non-irritant, pliable, workable and strong.

Late results of optical urethrotomy.

Of 46 patients who underwent optical urethrotomy for differing strictures of the urethra, 41 (89.1%) remained free of stricture symptoms at follow up 6 years later. The initial effectiveness of this procedure in improving stricture symptoms is sustained in the long term.

Laparoscopic versus open simple prostatectomy: a comparative study.

PURPOSE: Laparoscopic simple prostatectomy has recently been developed to remove large prostatic adenomas causing bladder outflow obstruction. To our knowledge the advantages of the laparoscopic vs the standard open approach to this procedure remain undefined. We compared laparoscopic and open simple prostatectomy. MATERIALS AND METHODS: Perioperative data on the first 30 consecutive laparoscopic simple prostatectomies performed by 1 surgeon were collected prospectively and compared with retrospectively collected data on a series of 30 consecutive open simple prostatectomies. A Millin and a transvesical-prostatic technique were used in the laparoscopic group and a transvesical technique was used in the open group. RESULTS: There was no significant difference in prostatic size, patient age or body mass index between the 2 groups. In the laparoscopic group the mean International Prostate Symptom score +/- SD improved from 22.4 +/- 6.9 to 5.7 +/- 3.6 and the urinary flow rate improved from 8.1 +/- 2.5 to 24.6 +/- 12.1 ml per minute (each p <0.001). Mean total blood loss (367 +/- 363 vs 643 +/- 647 ml), irrigation time (0.33 +/- 0.7 vs 4 +/- 3.5 days), duration of catheterization (4 +/- 1.7 vs 6.8 +/- 4.7 days) and hospital stay (5.1 +/- 1.8 vs 8 +/- 4.8 days) were significantly less in the laparoscopic group than in the open group. Mean operative time was longer in the laparoscopic group (115 +/- 30 vs 54 +/- 19 minutes). Of the 30 patients in the laparoscopic group 24 did not require bladder irrigation. There was no apparent difference in the incidence or severity of complications. There was no difference in perioperative parameters or functional results between the 2 different laparoscopic techniques. CONCLUSIONS: Laparoscopic simple prostatectomy has inherent advantages over the open technique. Further studies are indicated to determine whether this technique should be considered the treatment of choice for prostatic adenomas too large for safe endoscopic resection.

A temporary biological dressing in the treatment of varicose ulcers and skin defects.

Corethium 2 has been known to be a valuable biological dressing which encourages re-epithelization in cases of tissue loss, especially in varicose ulcers. It ensures a superior quality of healed tissue even in difficult chronic cases. It also reduces the overall treatment time and can be used as an out-patient dressing.