Estrogen regimen of women with endometrial carcinoma. A retrospective case-control study at Radiumhemmet.

In order to detect a possible association between exogeneous estrogens and endometrial cancer under Swedish circumstances, the previous use of estrogens among 622 cases of endometrial cancer 1974-77 has been compared with that of the average female population, represented by a randomly selected sample of 1 866 contemporaries to the cancer cases. Among women aged 50-69 years, 6-36 months of use of 'natural' and/or to a much lesser extent 'synthetic' estrogens was equally common in the two groups. However, starting in 1976, 3-6 years of use became increasingly more common among cancer cases. Taking 1974-77 together, cancer cases had been on such a long-term regimen more than 5 times as commonly as controls. Additional progestagen treatment was equally rare in the two groups. Tumors of estrogen users were of a significantly lower grade than those of non-users of the same age. While it cannot be concluded at this stage that estrogens are cocarcinogenic, the evident possibility motivates a somewhat cautious, restrictive approach to prescription. Progestagens could be added sequentially, though it is not yet verified that they abolish the association between endometrial cancer and estrogens that is now recognized by many investigators.

PIP: In order to detect a possible association between exogenous estrogens and endometrial cancer under Swedish circumstances, the previous use of estrogens among 622 cases of endometrial cancer, 1974-77, was compared with that of the average female population, represented by a randomly selected sample of 1866 contemporaries to the cancer cases. Among women aged 50-69 years, 6-36 months of use of natural and/or, to a much lesser extent, synthetic estrogens was equally common in the 2 groups. However, starting in 1967, 3-6 years of use became increasingly more common among cancer cases. For the period 1974-77, cancer cases had been on such a long-term regimen more than 5 times as commonly as controls. Additional progestagen treatment was equally rare in the 2 groups. Tumors in estrogen users were of a significantly lower grade than those of nonusers of the same age. While it cannot be concluded at this stage that estrogens are cocarcinogenic, the evident possibility motivates a somewhat cautious, restrictive approach to their prescription. Progestagens could be added sequentially, for although it is not yet verified that they abolish the association between endometrial cancer and estrogens, it is now recognized by many investigators.

Urethral pressure profile at pubococcygeal repair for stress incontinence.

The influence of pubococcygeal repair on the urethral pressure profile as well as the cure rate, technical operative results and side-effects have been studied in 16 severely stress-incontinent patients. The patients were followed during the first postoperative year in order to detect the possible long-term effects of devascularization, denervation and scarring on the urethral tone. Examination, using simultaneous urethrocystometry with recording of the urethral pressure profile at rest was undertaken preoperatively, 3 months postoperatively and one year postoperatively. Urethral functional length was not affected by the surgery. Urethral closure pressure was slightly reduced 3 months postoperatively and did not recover completely within the first postoperative year. Such a reduction in urethral pressure probably reflects damage to the urethral tissue due to devascularization and denervation. Its main clinical importance concerns cases of severe stress incontinence with a very low initial closure pressure in the urethra. Here, vaginal surgery may jeopardize that success of an otherwise technically irreproachably performed operation. On the whole, pubococcygeal repair is effective in achieving continence, although the side-effects call for careful selection of patients.

Endometrial cancer and exogenous estrogens.

PIP: In 622 cases of endometrical adenocarcinoma treated between 1974-1977 and in 1428 age-matched controls, the total use of synthetic and conjugated estrogens was determined from case reports, interviews, and written enquiries. It was found that conjugated estrogen use has increased, especially in the cancer group. For the years 1974, 1975, 1976, and 1977 the percentage of cancer patients with more than 6 months use of estrogens (not contraceptives) was 8.1, 17.0, 23.0, and 35.6 respectively as compared to 6.6, 8.6, 12.6, and 16.7 for controls. Use of less than 3 years duration was similar in controls and cases, but use for 3-6 years increased significantly among cancer patients (during 1974, 1975, 1976, and 1977 respectively, 2.3%, 4.5%, 11.5%, and 20.2% of the cases used estrogen as compared with 1.6%, 1.3%, 2.5%, and 3.5% of the controls). These initial findings indicate that long-term administration of estrogen should be limited to patients with distinct indications.^ieng

Cultures from different parts of the urethra in female urethral syndrome.

It is a common belief that the female urethral syndrome is an infectious disease, caused by ascending vestibular microorganisms or bacteria harboured in the paraurethral glands. To study the flora of different parts of the urethra in patients with urgency, cultures were obtained in 36 cases from the proximal urethra, the external urethral opening, the distal urethra after paraurethral massage and from the upper vagina for comparison. All locations were dominated by lactobacillae. Enterobacteria and anaerobic bacteria occurred in approximately one third of the cases at all sites, although only in small amounts in the urethra, especially in the proximal part. The urethral and the vaginal flora resembled each other very closely. Only in a few cases did a possible pathogen reside solely in the urethra, i.e. it could not be found in the vagina or in the vestibular flora. On the whole, no appreciable amount of any microorganism was present in the urethra or in secretion from the paraurethral glands. The clinical significance which a very small amount of enterobacteria or anaerobes may have in these locations remains to be established.

Mental factors influencing recurrence of stress incontinence.

At a recent follow-up of 51 women operated on for stress incontinence, there was an astonishingly high discrepancy between symptoms claimed by the patients and signs found by the physician. To examine the influence of certain mental factors on the recurrence of stress incontinence, the patients in the above-mentioned follow-up were tested with the Eysenck Personality Inventory test and the Sabbatsberg Depression Self-rating Scale test. The women with symptoms but no objective signs of stress incontinence showed a higher degree of both neuroticism and depression than the women of perfect health. Thus, in this group, it may be a question of aggravation of symptoms, which cannot be helped by a reoperation. Instead, these women might need psychiatric attention to relieve their psychosomatic symptoms.

Gracilis interposition in fistulas following radiotherapy for cervical cancer. A retrospective study.

Irradiation fistulas following treatment for cervical cancer are a great challenge even to a skilled surgeon. Because of ischemia and necrosis around the fistula, repair is possible only by interposition of viable tissue. Interposition of 1 or 2 mm gracilis has been used at Sabbatsberg Hospital since the beginning of the 1950's. 27 vesicovaginal fistulas have been treated with this method, with a cure rate of 60%. The corresponding cure rate for 16 rectovaginal fistulas was 43%. The mean diameter of the fistulas was 2.5 cm. Considering the unfavorable circumstances caused by radiotherapy, in some cases combined with fulguration, these results seem satisfactory.

Treatment of urgency by instillation of emepronium bromide in the urinary bladder.

The possibility of a purely local action of intravesically instilled emepronium bromide (Cetiprin) was investigated. Subjective reports and simultaneous urethrocystometry were used to assess such effect. In order to ascertain the purely local nature of effect, the serum was analyzed for freely circulating emepronium ion at increasing intravesical concentrations. No adverse effects were found at the highest dosage (100 mg in 100 ml saline solution), and the concentrations in serum were very low or were not detectable. The seemingly promising influence on micturition frequency and urge prompted a double-blind study of 20 patients with chronic urgency. In ten of them 100 mg emepronium bromide in 100 ml saline solution was instilled intravesically, while the other ten received only the same volume of saline solution. The symptoms were relieved in eight of the ten patients given emepronium bromide. The observation time was one week. The therapeutic possibilities were further evaluated in 24 women with frequency and urgency with or without urge incontinence. Emepronium bromide was intravesically instilled in the mentioned concentration and, if the symptoms were not totally relieved, this was repeated at weekly intervals. The maximum number of instillations was four and the observation time after the final treatment was at least three weeks. Frequency and urgency disappeared in approximately 70% of the affected women, nocturia in 60%, but urge incontinence in only 30%. Both frequency and urgency therefore were therapeutically influenced by intravesical instillation of emepronium bromide.

Influence of pubococcygeal repair on urethral closure pressure at stress.

Stress incontinence is cured or improved by surgical treatment but the immediate reason is obscure. Simultaneous urethrocystometry with urethral pressure profile recording at rest pre- and postoperatively has shown that the urethral pressure remains fairly unchanged by the operation. Similar measurements, but during stress, have been performed in eight women with stress incontinence before and after pubococcygeal repair with interest focussed on changes in pressure transmission from abdomen to urethra. We have found that the reason for cure is a greatly improved pressure transmission, probably depending on the firm support beneath the urethra postoperatively. Rotational descent is prevented and the "floor" beneath the urethra responds with good counterpressure at stress. The pressure transmission was as good at one year as at one month after surgery, pointing to a lasting result.

Urethral closure pressure with stress--a comparison between stress-incontinent and continent women.

Stress incontinence has been said to occur as a consequence of a low urethral pressure and defective pressure transmission from the abdomen to the urethra due to descent of the bladder neck area. Equipment suitable for dynamic pressure measurements has been used to analyse the losses of urethral pressure that lead to incontinence. The pressure transmission from abdomen to urethra was found to be incomplete in both continent and stress-incontinent women. There was also significant loss of smooth muscle tone in the urethral wall after repeated straining, leading to a still narrower margin between the urethral pressure and the leakage treshold in both continent and stress-incontinent women. The main factor determining the degree of continence or incontinence seemed to be the urethral closure pressure at rest . As long as this pressure is sufficiently high, leakage during sudden stress will not occur.

Pressure transmission to the pre-urethral space in stress incontinence.

Pressure transmission from the abdomen to the pre-urethral space has been studied in stress- incontinent women and in some women following pubococcygeal repair for stress incontinence. Pressure was recorded at different levels of the pre-urethral space and simultaneously in the bladder. Simultaneous measurements inside and outside the urethra at different levels above the external urethral meatus showed that an intra-abdominal pressure rise was transmitted via the pre-urethral space to the urethra. Pressure was transmitted almost in full to the surroundings of the lower-most part of the bladder, but outside the functional urethra, transmission was successively more defective along the urethra towards the external meatus. Therefore, a short functional length and a distal maximal pressure plateau in the urethra, as in stress incontinence, is a disadvantage. Pressure losses amount to 1/3 or more. Pressure transmission could be improved to "supranormal" values by establishing firm support for the urethra, thereby allowing a minimum of rotational descent with stress and providing good counterpressure.

Urethral pressure profile before, during and after pubococcygeal repair for stress incontinence.

In two groups of women the urethral pressure profile was recorded using a microtransducer catheter. Both groups were of approximately the same age, one consisting of continent women, the other of women with severe stress incontinence. Sixteen stress incontinent woman were examined before and after pubococcygeal repair and 10 of these were also examined during the operation. The two groups were compared for differences in the urethral pressure profile in the continent and incontinent states. The stress incontinent women had a significantly shorter functional length of the urethra (10 mm) but the same maximal urethral pressure as continent women. Remarkable changes in these parameters were seen during the operation. However, at the examination 3 months postoperatively, they had totally disappeared. The only change in the urethral pressure profile which persisted after the operation was a higher pressure in the proximal part of the urethra so that a urethral maximal pressure plateau had been established. This plateau was also seen, on a higher level, in the continent state.

The margin to incontinence after three types of operation for stress incontinence.

Three of the most widely used operations for stress incontinence--urethropexy ad modum Marshall-Marchetti-Krantz, pubococcygeal repair according to Ingelman-Sundberg and the Zoedler sling operation--were studied concerning urodynamic results. Simultaneous urethrocystometry with recording of the urethral pressure profile was used to quantify postoperative continence. The urethral pressure profile at rest, the transmission of pressure from abdomen to urethra and the efficiency of the smooth muscle in the urethral wall and its supporting tissues in a dynamic situation were compared with preoperative findings. Equally good results were obtained with the Marshall-Marchetti-Krantz and the Ingelman-Sundberg operation, which improved pressure transmission.

Urethrocystometric findings in urgency.

15 women with chronic urgency have been examined with simultaneous urethrocystometry during an exacerbation of their disease. A thin microtip transducer catheter was used for pressure registrations. Both the bladder pressure and the maximal urethral pressure in the erect position were recorded during slow filling of the bladder. Although the patients had severe symptoms of frequency and in some cases urge incontinence in daily life, bladder capacity was almost normal. The desire to void appeared early but was not accompanied by a rise in bladder pressure. Even when the patients felt violent tenesmi, the bladder pressure curve remained completely calm. Only the urethral pressure reacted, with rapid rises and falls of 20--40 mm Hg, as the patients desperately tried to hold urine. Thus, no detrusor activity, but only a certain instability of the urethral pressure accompanied the subjectively imperious desire to void in urgency.

The effect of alpha-adrenergic stimulation in stress incontinence.

The urethra is innervated by adrenergic fibres and its smooth muscle is equipped mainly with alpha-adrenoreceptors. Norephedrine chloride, which is an alpha-stimulating agent, has been proposed as therapy for stress incontinence, since it was shown to increase the maximum urethral pressure at rest. For further study of the effect of norephedrine chloride on the urethal closure pressure at rest and in a dynamic situation, we examined ten severely stress-incontinent women before and after three weeks of treatment with this agent (100 mg by mouth twice daily). The urethral closure pressure at rest, between coughs of varied strength and at the precise moment of stress were recorded. The margin to leakage, the tone of the urethral wall and the transmission of pressure from abdomen to urethra were also among the estimated factors. No improvement was found in any of these respects. Alpha stimulation in this form therefore seems ineffective in severe stress incontinence and is not an alternative to surgical treatment.

Intra-urethral and intra-vesical pressure in continent women.

Two age-groups of continent women were examined regarding the pressures in the urethra and the bladder, using a standardized recording technique with a microtransducer catheter elaborated in 1974 by Ulmsten-Asmussen. The two groups of women (mean age 28 and 54 years respectively) were examined concerning their urethral pressure profile at every 100 ml bladder filling until the maximal bladder capacity had been reached. The functional length of the urethra and the bladder pressure were the same for all women but the maximal urethral pressure decreased significantly with age (mean 61.5 and 39 mmHg in the two groups respectively). At increasing bladder filling only the younger group was able to respond with an increase in the maximal urethral pressure. The bladder volume at which severe tenesmi occurred was significantly higher in the elderly group.