Experience with an assay for prostate-specific antigen and transrectal ultrasonography in the diagnosis of prostate cancer.

OBJECTIVE: To assess the detection of prostate cancer using the Ciba Corning ACS 180 prostate-specific antigen (PSA) assay and transrectal ultrasonography (TRUS) in a district general hospital. PATIENTS AND METHODS: In a preliminary study, the serum PSA level in 130 patients was measured using both the Ciba Corning and the Hybritech Tandem-R PSA assay and the results assessed using linear regression analysis. A further study comprised 204 consecutive patients who underwent TRUS and biopsy. The histology of the prostatic biopsies was analysed according to the pre-biopsy PSA level (Ciba Corning assay), digital rectal examination (DRE) and TRUS findings. RESULTS: The PSA levels measured using the Ciba Corning assay were about 50% higher than those using the Hybritech Tandem-R assay. Of 204 men who had TRUS and biopsy. 56 (28%) had detectable prostate cancer, but no patient with a PSA of < 6.0 ng/mL had. Five of 47 (11%), 21 of 83 (25%) and 30 of 65 (46%) patients with PSA levels in the range 6.1-15.15.1-30 and > 30 ng/mL, respectively, had cancer detected. When the DRE was negative, 18 of 111 (16%) patients had a positive biopsy, compared with 38 of 93 (41%) patients when the DRE was positive (P < 0.001). In men with a PSA level of 6.1-15.0 ng/mL, positive biopsies were found in 3% when the DRE was negative, compared with 27% when it was positive (P < 0.025). A TRUS abnormality was detected in 54 of 204 (26%) patients, of whom 25 (46%) had positive biopsies. Of these 54, there were 43 with hypoechoic lesions, of whom 22 (51%) had positive biopsies. The cancer detection rate was higher when both TRUS and DRE were positive (62%), with the highest detection rate (86%) occurring when the PSA level was also > 30.0 ng/mL. When the DRE was positive, cancer was detected in 21 of 34 (62%) patients with a positive TRUS, but only in 17 of 59 (29%) patients with a negative TRUS (P < 0.005). However, when the DRE was negative there was no significant difference in the cancer detection rates for TRUS-positive and TRUS-negative patients, where four of 20 and 14 of 91 (15%) patients were found to have cancer, respectively. CONCLUSIONS: The positive biopsy rates in this study were comparable with those from similar studies using other PSA assays. When the DRE was negative there was a low detection rate for cancer of 3% for men with PSA levels of 6.1-15.0 ng/mL. In patients with an elevated PSA level but a negative DRE, the positive biopsy rate for TRUS-negative patients did not differ from TRUS-positive patients, indicating the importance of random systematic biopsies.

Hormonal cytoreduction and radiotherapy for carcinoma of the prostate.

We report the effect on prostatic volume of the administration of the luteinising hormone-releasing hormone (LHRH) analogue goserelin in 22 patients with locally advanced carcinoma of the prostate; 20 achieved a significant reduction in volume, the median volume being 66 ml before treatment (range 40-130) and 30 ml after 17 weeks (range 13-47). If used before external beam radiotherapy (RT), volume reduction will permit smaller boost fields and thus potentially reduce adverse radiotherapy effects. In addition, reducing tumour volume before RT may lead to an increase in local control. We discuss the possible role of hormonal volume reduction in the management of prostatic cancer.

Urinary tract metastasis from renal carcinoma.

Five patients with urinary tract metastases from renal carcinoma are presented. In 4, urinary tract metastasis occurred in the absence of spread elsewhere. The initial presentation in 1 patient was ureteric obstruction; 3 others re-presented with haematuria and the fifth patient was diagnosed post mortem. Metastatic sites included ipsilateral ureter, contralateral ureter, ureteric stump, bladder and prostatic fossa. After previous nephrectomy for renal carcinoma, urinary metastases, although rare, should be considered and investigation of unexplained haematuria should include the ureteric stump. Useful palliation and possibly cure can be achieved by resection of these lesions.

Role of continent suprapubic diversion in pelvic cancer.

Seventeen patients with either current (n = 14) or previous (n = 3) pelvic malignant disease underwent continent urinary diversion using the Mitrofanoff principle in 16 and a Kock pouch in 1. Eight patients had bladder carcinoma, 6 had gynaecological malignancy, 2 had rectal cancers and 1 had a squamous cell carcinoma of the perineum. Fourteen underwent synchronous exenterative surgery and continent suprapubic diversion; plastic reconstructive procedures were required in 4. There were 2 post-operative deaths and 5 patients have developed further tumour recurrence. Continence was satisfactory in all patients with a median interval of intermittent self-catheterisation of 4 h.

Imaging properties of polydioxanone and titanium ligating clips following para-aortic lymphadenectomy for testicular cancer.

Stainless steel ligating clips produce serious artefacts on CT scans. Polydioxanone (PDS) and titanium ligating clips were used in 15 patients during para-aortic lymphadenectomy for residual metastatic testicular teratoma following chemotherapy, and follow-up CT images were compared with those following the use of stainless steel ligating clips. PDS ligating clips did not produce any artefacts and were progressively absorbed. Titanium ligating clips produced artefacts similar to but less intense than those of stainless steel. PDS ligating clips should be used when follow-up CT scanning is important.

Transurethral resection of prostate under sedation and local anesthesia (sedoanalgesia). Experience in 100 patients.

One hundred male patients (average age 68.2 yrs) with acute retention (n = 20) or with symptoms of outflow obstruction (n = 80) underwent transurethral resection of the prostate (TURP) under sedation (midazolam) and local anesthesia (lidocaine)--referred to as sedoanalgesia technique. Procedures lasted twenty-four minutes on average (range 15-35 min), and the weight of prostatic tissue resected ranged from 2-35 g (average 11.1 g). There were no complications related to the use of midazolam or lidocaine. The technique of sedoanalgesia proved safe and acceptable to all patients regardless of their pre-existing medical condition. Where the weight of prostate to be resected is estimated to be less than 40 g, TURP under sedoanalgesia proves an effective alternative to general or regional anesthesia.

The relationship of plasminogen activators and oncogenes to tumour invasion.

Accruing evidence suggests an association between increased activity of plasminogen activators and transformed cells, and urokinase activity with tumour aggressiveness. The PIP2 pathway seems to provide a link between oncogene-associated transformation, cellular proliferation, plasminogen-activator expression and tumour invasion and metastasis.

Rigid versus flexible cystoscopy. A controlled trial of patient tolerance.

The cost-efficiency and time-saving associated with out-patient flexible cystoscopy have propagated its use nationwide. However, only minimal attention has been paid to the feelings of patients exposed to this physically and emotionally invasive technique. We studied 53 consecutive patients attending for check cystoscopy at the time of their first flexible cystoscopy. Acting as their own historical controls, their feelings about rigid cystoscopy under general anaesthesia and subsequent flexible cystoscopy under local anaesthesia were assessed: 6/53 (11%) preferred rigid cystoscopy under general anaesthesia. The only significant association with their dislike of flexible cystoscopy, was their desire to stay in hospital overnight. It was concluded that with careful counselling and attention to individual needs, the preference for flexible cystoscopy over rigid cystoscopy under general anaesthesia can approach 100%.

Plasminogen activators in experimental colorectal neoplasia: a role in the adenoma-carcinoma sequence?

An important step in the transition from adenomatous polyp to invasive carcinoma is the degradation of the epithelial basement membrane. By the generation of plasmin, plasminogen activators may play an important role in regulating the extracellular protease activity required for this event to occur. The production of biofunctional urokinase and of tissue plasminogen activator was therefore investigated in the dimethylhydrazine induced rat model of colorectal neoplasia. Both adenomatous polyps (p values less than 0.001) and colorectal carcinomas (p values less than 0.001) were demonstrated to produce a significant excess of both urokinase and tissue plasminogen activator when compared with macroscopically normal colon. There was, however, no increased production of either enzyme by macroscopically normal preneoplastic colon when compared with control colon. This enhanced capacity of colorectal tumours to produce plasminogen activators and generate plasmin is thus a feature of both the premalignant as well as the malignant phenotype. These enzymes may contribute to the malignant potential of adenomatous polyps and to the invasive capacity of established carcinomas.

Role of urokinase in colorectal neoplasia.

The biofunctional activity of the plasminogen activators urokinase and tissue plasminogen activator has been measured in extracts from 50 colorectal carcinomas and 21 adenomas using a bioimmunoassay. Compared with control mucosa urokinase activity was significantly elevated in adenomas (P less than 0.001) and carcinomas, levels being significantly higher in carcinomas (P less than 0.05). In contrast tissue plasminogen activator activity was reduced in adenomas (P less than 0.01) and carcinomas, levels being significantly lower in carcinomas (P less than 0.01). Although enzyme activity did not relate to Dukes' stage or histological grade urokinase activity was higher in carcinomas with venous invasion (n = 17, P less than 0.05), in those with moderate or extensive local spread (n = 27, P less than 0.05) and in cases where a palliative resection only was feasible because of advanced disease (n = 8, P less than 0.05). Urokinase has been implicated in tissue degradation as well as fibrinolysis and may play a role in tumour invasion and metastasis in human colorectal neoplasia.

Plasminogen activators in human colorectal neoplasia.

A crucial step in the transition from adenomatous polyp to invasive colorectal cancer is the degradation of the epithelial basement membrane. Plasminogen activators may play a part in regulating the extracellular protease environment necessary for this to occur. Both functional and antigenic activity of the two principal activators of plasminogen, tissue plasminogen activator and urokinase, were measured in 30 colorectal cancers, matched samples of mucosa, and eight adenomatous polyps. Both polyps (p less than 0.01) and carcinomas (p less than 0.001) had raised urokinase activities compared with normal mucosa, the activity being highest in the carcinomas. Activity of tissue plasminogen activator, however, was diminished in both polyps (p less than 0.01) and carcinomas (p less than 0.001) compared with normal mucosa, the values being lowest in carcinomas. Plasmin generation by urokinase--in contrast with tissue plasminogen activator--is fibrin independent and thus less subject to physiological control.

Surgery for peptic ulceration associated with hypergastrinaemia.

Between 1971 and 1983, 31 males and 13 females were found to have peptic ulceration associated with hypergastrinaemia. An antral G-cell lesion was present in 11 (25 per cent) and a gastrinoma in 14 (32 per cent). There were 11 patients with multiple endocrine adenomatosis (MEA) (25 per cent) and 4 (9 per cent) with primary hyperparathyroidism. Four patients (9 per cent) were unclassified. Length of history and level of gastrin did not differentiate between the groups and an average of 2.5 operations was performed per patient, while the overall mortality was 27.3 per cent. The patients with G-cell lesions were significantly younger than all the other groups (P less than 0.01). Partial gastrectomy adequately treated G-cell hyperplasia. Total gastrectomy was required to treat pancreatic gastrinomata but additional pancreatic resection did not improve the outcome. In MEA, parathyroidectomy did not influence the treatment of a gastrinoma. This is the first recorded experience of surgery for hypergastrinaemia in the United Kingdom and the outcome of such a retrospective study may be a guide to the future management of these conditions.

Preliminary experience with defibrotide in severe lower limb ischaemia.

Eight patients with severe lower limb ischaemia, aged 65-80, received defibrotide intravenously for periods from 5 to 21 days (mean 13 days). All patients had intractable rest pain. Five had ischaemic ulcers and 3 had minor gangrene. Five had previous arterial surgery and 6 lumbar sympathetic ganglion injections. Pretreatment ankle pressure indices ranged from 0 to 0.5 (mean 0.19). Rest pain, sleep disturbance and analgesic requirement were assessed on a nominal scale. Rest pain improved in 4 and sleeping pattern in 2 patients. One patient showed a diminution in analgesic requirement. Pressure indices improved in 5 patients. Amputation was performed in 4 patients. Adverse reactions included vomiting and diarrhoea (2), thrombophlebitis at infusion site (3) and generalized skin reaction (1). All patients had 'end-stage' peripheral vascular disease but some showed symptomatic benefit. Further evaluation of defibrotide is indicated.