Intermittent androgen deprivation after PSA-complete response as a strategy to reduce induction of hormone-resistant prostate cancer.

OBJECTIVES: The increasing interest in exploring the use of intermittent androgen deprivation in prostate cancer has prompted a retrospective review of patients who elected to stop treatment. METHODS: Case records were reviewed. RESULTS: Twenty patients after 3 to 48 months (median 12) of endocrine therapy elected to stop therapy. Thirteen subsequently relapsed after a median observation of 9 months. Seven of 20 patients continue progression-free for 9 to 42 months (median 33). After second-line therapy, 75% of patients with a relapse remain progression-free at 2 years. Progression-free survival was higher in patients at Stage M0 (82% at 1 year) versus M+ (29% at 1 year). CONCLUSIONS: With 10 of 13 patients demonstrating an ongoing second PSA response, 45% of patients showing no progression, and 85% alive at 3 years, these results support findings from previous publications that suggest that there are no major risks with use of intermittent hormone therapy. However, in the future, there is an urgent need that such studies should be randomized and done in the context of audit-based research and development programs. The resources released could then be invested with respect to further improvements in treatment of prostate cancer, possibly considering such a combined approach with immunotherapy as an alternative to surgery or radiotherapy for early disease in elderly patients with long PSA-doubling time.

Testis conservation studies in germ cell cancer justified by improved primary chemotherapy response and reduced delay, 1978-1994.

OBJECTIVE: To investigate the need for the continued encouragement of early diagnosis of germ cell cancer of the testis, in view of the prevailing cure rate of 95%. PATIENTS AND METHODS: The study comprised a retrospective review of 453 unselected and previously untreated patients referred to one centre between 1978 and 1984, comparing the delay from first symptoms with the histological diagnosis. RESULTS: With a delay of < 30 days, 20% of patients had overt metastases at presentation and if the delay was > 4 months. 55% had metastases (chi-squared trend = 15.9, P < 0.001); 18% of Stage-1 patients under surveillance with a delay of < 30 days relapsed, compared with 38% of those with a delay of > 4 months. During the period 1978-1983, 16% of patients were seen after a delay of < 60 days, during the period 1984-1988 the proportion was 22% and during 1989-1994, 31% (chi-squared trend = 8.2, P < 0.004). There was a non-significant trend for a more prolonged delay in those aged < 21 years and > 40 years. Thirty-two patients had chemotherapy with the primary tumour in situ; at orchidectomy, 13 of 18 had no viable malignancy and four of five with viable malignancy also had drug-resistant metastases. Fourteen did not undergo orchidectomy; within a median follow-up of 9 years, one developed a second (histologically different) tumour after 12 years. The outcome of preliminary attempts to use neoadjuvant chemotherapy with or without partial orchidectomy for patients with tumours in a solitary testis is discussed. CONCLUSION: These findings clearly justify the continued encouragement of early diagnosis, possibly best performed as part of an extended educational programme of genital health at puberty. The long-term potential for testis conservation should be explored initially in tumours in a solitary testis.

Pelvic floor physiology in women with faecal incontinence and urinary symptoms.

Anorectal manometry, balloon proctometrography, measurement of anorectal angles and videourodynamics were used to investigate 45 asymptomatic women and 13 with faecal incontinence and urinary symptoms, nine of whom also had stress urinary incontinence. The anorectal angle was measured and videourodynamics performed on 17 constipated women with urinary symptoms. Mean (s.e.m.) values obtained with anorectal manometry were lower in women with faecal incontinence and urinary symptoms than in controls (maximum resting pressure 42.5(8.1) versus 82.5(9.3) cmH2O, P = 0.001; maximum attained pressure 80.5(13.7) versus 216.2(11.2) cmH2O, P = 0.001; maximum squeeze increment 35.3(7.5) versus 141.6(10.0) cmH2O, P = 0.001), indicating a weakened puborectalis and external anal sphincter. Mean(s.e.m.) anorectal angles at rest, squeeze and strain were all significantly greater in the doubly incontinent women than in those with constipation (114(3.8) versus 93(5.9) degrees, P = 0.01; 103(2.5) versus 78(3.5) degrees, P < 0.001; 120(2.9) versus 104(4.2) degrees, P = 0.01). Urinary incontinence was worse in the doubly incontinent than in the constipated women (eight of nine versus one of eight with grade 2a or higher, P = 0.002). These results suggest that doubly incontinent women have a significantly weakened pelvic floor and that this should be taken into account before any planned surgery for urinary incontinence.

Simultaneous dynamic electromyographic proctography and cystometrography.

The rectum and bladder share a common origin and work in harmony; disturbance in one may lead to a similar problem in the other. The two have, however, not previously been investigated dynamically and simultaneously. A new system has been devised allowing dynamic integrated electromyographic proctography to be performed simultaneously with cystometrography in 41 patients (28 women and 13 men). Of 16 women with chronic constipation who underwent the combined study, ten were shown to have obstructed micturition. Eight of these ten women exhibited an inappropriate contraction of the puborectalis muscle during micturition, compared with one of the six with normal micturition (P = 0.02). Of the patients with obstructed micturition, seven of eight women with a rectocele also had anismus, compared with none of four women with a rectocele among those who were able to micturate normally (P = 0.02). Eight of the ten women with obstructed micturition thus had a proctological abnormality that explained the urological symptoms. Of 12 women with idiopathic faecal incontinence who underwent the combined study, eight were shown to have genuine stress incontinence of urine. In seven of these the severity was shown to be of type 2a or greater, indicating that pelvic floor dysfunction may be the causal factor of both rectal and urinary symptoms. The combined study shows abnormalities in one system that could explain similar symptoms in the other.

The quality of life after radical radiotherapy for bladder cancer.

The quality of life in 72 patients who had shown a complete response to radiotherapy, using a modified bladder symptom score and the Nottingham health profile, was compared with the quality of life in a similar control group matched for age and sex. There was no significant difference in either group. The records of 69 patients who had undergone post-radiation salvage cystectomy were reviewed, looking specifically at surgical complications. There were 3 post-operative deaths (5%), 3 pulmonary emboli and 3 fistulae--with some overlap of complications. Five patients who underwent cystectomy for intractable symptoms in the apparent absence of recurrent tumour were found to have residual cancer in the excised specimens.

Long-term results of treatment of urethral injuries in males caused by external trauma.

Of 134 males with traumatic rupture of the urethra seen between 1967 and 1989, 10 have been lost to follow-up and 124 have been followed up for 1 to 22 years (mean 8); 100 patients had a pelvic fracture (3 with associated rectal injury) and 24 had perineal injuries. Prior to referral 31 patients (25%) had undergone treatment in addition to suprapubic cystostomy. Wherever possible, strictures were managed by optical urethrotomy (33) or intermittent dilatation (4). In 2 patients only a suprapubic cystostomy was possible. Skin inlay urethroplasty in 1 or 2 stages was performed in 75 cases, an end-to-end anastomosis with or without resection of the symphysis pubis in 7 and a scrotal tube pull-through in 3. The immediate and long-term results depended on the severity of the original injury. With minimal displacement the management was simple and the long-term prognosis good, a single urethrotomy being sufficient in 22 patients. Where there was considerable displacement the initial management was more difficult and there was a high incidence of long-term complications: of 73 patients treated by urethroplasty or end-to-end anastomosis, significant post-operative infection occurred in 11 (15%) and restenosis in 15 (20%), of whom 7 required a revision urethroplasty. Data in respect of potency were recorded in 80 patients: 28 of these were impotent, 20 of the 28 having sustained an injury with considerable displacement.

Long-term results of one-stage scrotal patch urethroplasty.

Of 211 patients with urethral strictures undergoing one-stage dartos pedicled island patch urethroplasty between 1970 and 1987, 194 have been followed up from 3 to 20 years. There was 1 post-operative death (from hepatitis). During the period of follow-up, strictures recurred in 14 patients (7%), some of them as late as 15 years after an apparently successful urethroplasty. Calculi forming on hairs required treatment in 6 patients (3%) and it was necessary to revise a redundant skin pouch in 6.

Ethics, logistics and a trial of transurethral versus open prostatectomy.

An increased long-term morbidity rate after transurethral compared with open prostatectomy has recently been claimed on the basis of retrospective studies of operations done up to 20 years ago. These studies have led to a demand for a prospective trial. Most reports show that peri-operative mortality following prostatectomy is virtually confined to unfit men over 80 years old. Before agreeing to participate in a trial we examined our operative mortality in this group of patients. Between 1981 and 1987, 123 octogenarians underwent transurethral prostatectomy: 64 operations were elective and 59 were performed for retention. There were 2 operative deaths (1.6%), both from gram-negative septicaemia despite prophylactic antibiotics. There were no additional deaths in the first 12 months following surgery. Few of these patients would have been considered fit to undergo an open prostatectomy. Any proposed randomised trial would have to exclude such high risk patients until it can be shown that open prostatectomy is equally safe.

Transurethral resection syndrome. A prospective study.

Significant hyponatraemia has been reported following transurethral prostatectomy (TURP) in 11-41% of cases. The majority of previous studies have been performed retrospectively. A prospective study was undertaken of 100 patients undergoing TURP. In all, a 24-Charr sheath with non-irrigating, resectoscope and 1.5% glycine as irrigant was used. Volume of irrigant used, weight of prostate and length of procedure were recorded. Serum electrolytes were measured at anaesthetic induction and immediately on transfer to the recovery room. In none of the 100 patients was there a statistically significant fall in serum sodium following resection. No clinical changes of transurethral resection (TUR) syndrome occurred. This study confirms that TUR syndrome and a significant fall in serum sodium can be virtually prevented in TURP and the use of an irrigating resectoscope or a trocar in the average case is not necessary.

Early repair of iatrogenic injury to the ureter or bladder after gynecological surgery.

Contrary to the traditional doctrine of delayed intervention in post-hysterectomy injuries of the ureter or bladder, the policy at our department has been to operate as soon as possible after the diagnosis is made. Of 68 patients (25 with vesicovaginal fistulas and 43 with ureteral injuries) early intervention was possible in 40 (59%). Primary healing was obtained in all patients. These results suggest that there is no disadvantage in early repair.

Operative factors & tumor membrane antigen changes in escape from immune surveillance of bladder cancer.

1. Survival of skin allografts in mice is increased in proportion to the duration of anaesthesia to a degree that is equivalent to that achievable with a major immunosuppressive agent such as azothiaprine or antilymphocyte serum. 2. Immune cytochemical studies have demonstrated that bladder tumors which metastases express beta HCG and show variable degrees of loss of HLA class I antigens--features which mimic the behaviour of human trophoblast in protecting the foetus from maternal rejection. It is concluded that there may be a case for using such prognostic factors to define a sub group of patients in whom reconstruction of the bladder following cystectomy should be deferred until the patient has survived without metastases for a prolonged period.

Prediction of response to radiotherapy in invasive bladder cancer.

The original pre-treatment histological sections from 125 patients with invasive (T2/T3) transitional cell bladder cancer treated by radical radiotherapy were studied; 63 tumours responded completely to radiation and 62 did not; 55 of 72 tumours containing areas of squamous metaplasia and 27 of 36 staining for beta-human chorionic gonadotrophin failed to respond to radiotherapy; 26 of 28 tumours showing both squamous metaplasia and beta-human chorionic gonadotrophin did not respond to radiation, whereas 40 of 45 tumours without either of these features responded. The DNA ploidy of 86 tumours in the series was measured by flow cytometry; 11 of 27 aneuploid and 30 of 59 diploid tumours responded to irradiation. Squamous metaplasia and beta-human chorionic gonadotrophin in bladder cancer indicate resistance to radiotherapy but DNA ploidy does not.

The fate of G3pT1 bladder cancer.

Poorly differentiated (G3) cancers are known to have a worse prognosis than other superficial bladder tumours. In the period 1976 to 1987, 53 patients with G3pT1 disease were treated by radical radiotherapy with a 5-year survival rate of 64%. Thirteen patients (25%) developed an invasive tumour during the follow-up period. The presence of secondary carcinoma in situ was associated with a poor prognosis. These results are better than those reported for transurethral resection alone and suggest that radiotherapy is the treatment of choice in G3 superficial tumours.

Beta human chorionic gonadotrophin in serum and urine. A marker for metastatic urothelial cancer.

Beta human chorionic gonadotrophin (beta HCG) was measured in 127 urine and 85 serum samples from 175 untreated patients with urothelial cancer. Serum levels of beta HCG were substantially elevated in 16 of 21 patients (76%) with widespread metastases but in only 2 of 64 patients (3%) with disease confined to the pelvis. Urine beta HCG levels were moderately raised in 11 of 25 patients (44%) with locally advanced disease, but greatly elevated in 5 of 7 patients (71%) with metastases. Measurement of serum and/or urine beta HCG appears to be an efficient diagnostic marker for the presence of distant metastases in bladder carcinoma.