Carcinoma of the prostate; diagnosis and treatment

About 28 per cent of men between the ages of 71 and 75 have cancer of the prostate. Many of them do not die of the disease, but with the life span ever increasing, this problem is becoming more important. In the early stages the condition is asymptomatic; when the symptoms of urinary obstruction arise, the cancer is usually too advanced for cure. Cure depends on early diagnosis and, therefore, on routine rectal examination. The solitary hard nodule of early prostatic cancer becomes a stony hard fixed prostate as the condition progresses. X-ray and acid phosphatase studies are of help only after the cancer has metastasized. As many as 50 per cent of patients with rectally palpable early carcinoma of the prostate can be cured by radical perineal prostatectomy. Often, simple enucleation or transurethral resection is sufficient to effect cure in the case of occult carcinoma. However, some observers believe that when cancer is detected by microscopic examination of a prostate that has been removed, a radical operation should be done as soon after the initial operation as feasible. Early orchidectomy and estrogen therapy are of considerable help in slowing the process of advanced prostatic cancer and may postpone the need of transurethral resection to relieve obstruction. When these measures fail, bilateral adrenalectomy, cortisone therapy, pituitary irradiation, and pituitary extirpation have been employed, with moderate success, in an effort to diminish the androgen level.     

Serum concentrations of deoxycorticosterone in women during the luteal phase of the ovarian cycle are not suppressed by dexamethasone treatment

We determined the serum levels of deoxycorticosterone (DOC) in plasma of six healthy, apparently ovulatory women during the mid-follicular and mid-luteal phases of their ovarian cycles; and we evaluated the effect of dexamethasone (1 mg by mouth) on the concentrations of DOC and cortisol in serum at times when plasma progesterone levels were high or low. The serum levels of DOC, unlike those of cortisol, did not vary significantly in single blood samples obtained in the morning (8-10 a.m.) and afternoon (3-5 p.m.); and serum DOC levels in women were significantly higher (P less than 0.05) during the mid-luteal phase than during the mid-follicular phase of the cycle. There were unmistakable diurnal variations in serum levels of cortisol, and cortisol concentrations were reduced to less than 20% of pretreatment levels after the ingestion of 1 mg dexamethasone during the mid-follicular or mid-luteal phase. The serum concentrations of DOC were reduced only to approx 70% of pretreatment levels after dexamethasone ingestion during the follicular phase. The serum levels of DOC did not decline significantly after administration of dexamethasone during the mid-luteal phase, when progesterone levels in serum are high (14-16 ng/ml). Blood samples also were obtained at hourly intervals during the 24 h before and after dexamethasone administration in one woman during the follicular phase and in another woman the during the early luteal phase (progesterone levels = 1-3 ng/ml) of the ovarian cycle. DOC levels (pre-dexamethasone) fluctuated in synchrony with those of cortisol in the woman studied during the follicular phase but not in the woman studied during the early luteal phase of the cycle. In the post-dexamethasone period, plasma cortisol levels were suppressed for at least 24 h in both women whereas DOC levels were decreased only partially. We conclude that plasma DOC is derived from both adrenal secretion and from extraadrenal 21-hydroxylation of progesterone--the latter source of DOC is not affected by dexamethasone suppression of ACTH secretion.     

Mild and moderate dyskaryosis: can women be selected for colposcopy on the basis of social criteria?

OBJECTIVE--To describe the distribution of cervical intraepithelial neoplasia grades among women with mild and moderate dyskaryosis after a single cervical smear and to determine whether social criteria could help identify women who are at increased risk of grade II or III disease. DESIGN--Cross sectional analysis within a randomised prospective study. Subjects had a repeat smear, a colposcopic examination, and an excision biopsy of the transformation zone. In addition, women were asked to complete a social questionnaire. SETTING--Colposcopy clinic, Aberdeen. SUBJECTS--228 women with a single smear test showing mild or moderate dyskaryosis. MAIN OUTCOME MEASURES--Histology, age, sexual and contraceptive history, cigarette smoking. RESULTS--159 (70%) women had cervical intraepithelial neoplasia grades II or III. Among current smokers the prevalence of grade II and III disease was higher in women who smoked greater than or equal to 20 cigarettes a day (84%) than among those who smoked less (66%; p less than 0.04). Women with more than one sexual partner also had a higher prevalence (75%) than women with only one partner (50%; p = 0.0028). Use of oral contraceptives and younger age were not significantly associated. The prevalence of grade II or III disease was up to 66% in the lower risk groups. CONCLUSIONS--Because of the high prevalence of cervical intraepithelial neoplasia grades II and III in both the high and the low risk groups social factors are not useful for selecting women with mild or moderate dyskaryosis for either early referral to colposcopy or cytological surveillance.     

Amenorrhoea after Discontinuing Combined Oestrogen-Progestogen Oral Contraceptives

Out of 210 women seen at the Middlesex Hospital with secondary amenorrhoea the 63 who developed it after stopping oral contraceptives were fully investigated. Five had organic disease sufficient to account for the amenorrhoea (one had severe diabetes, one a pituitary tumour, and three premature ovarian failure); two patients had galactorrhoea (one of whom also had the pituitary tumour); two had anorexia nervosa.Of the 63 women 40 (63%) had suffered from amenorrhoea or prolonged or irregular menstrual cycles before taking the pill, and this suggested that combined oestrogen-progestogen oral contraceptives should be used with caution for women with irregular menstruation.Nineteen patients wished to become pregnant and 12 have so far done so after treatment with clomiphene or gonadotrophins.In another study 204 women recorded when their first menstrual cycle occurred after stopping the pill. Seventy-four had a cycle longer than five weeks but only five exceeded three months, and only one of the five had more than six months'' amenorrhoea. These results confirm that the incidence of amenorrhoea after stopping oral contraceptives is low.     

Referral and experience with genetic testing among women with early onset breast cancer

The purpose of this study was to determine whether physicians refer women with early onset breast cancer for genetic testing for BRCA1 and BRCA2, and how women respond to being offered testing and use the results. A web-based survey was distributed to 1221 women with early onset breast cancer. The survey included 158 questions divided into the following sections: demographics, family history of cancer, medical history, treatment history, and experience with genetic testing. Of 551 women diagnosed since 1993 who responded to the survey (45.1%), less than half (45%, n = 246) had ever discussed genetic testing with their physician and/or been referred to see a genetic counselor. Women with a family history of cancer (53%) and Ashkenazi Jewish women (81%) were more likely to have been referred. Of those who had discussed testing, 60% had undergone or were interested in testing. Overall 92 women were tested and 19 (20.6%) of these tested positive for a deleterious BRCA1 or BRCA2 mutation. Fourteen (74%) who tested positive subsequently underwent prophylactic surgery. Satisfaction with counseling and the decision to be tested was high. Among women who were not offered testing, the fact that the test had not been offered by their physician (89%), and fear of discrimination (83%) were the two most frequently cited factors for lack of interest in testing. A substantial number of women are not being referred to genetic counseling and/or testing after a diagnosis of early onset breast cancer. Among those who were tested, there was high interest in prophylactic surgery after confirmation of a BRCA1/2 mutation.     

Fates and Roles of the Presumptive Organizer Region in the 32-cell Embryo in Normal Development of Xenopus laevis

Using 32-cell Xenopus embryos series of extirpation experiments were performed in order to clarify whether or not the dorsal equatorial blastomeres were committed to differentiate to the axial mesodermal structures. First, these blastomeres designated as B1, B1', C1 and C1' and C1' were labeled using the technique of HRP injection or vital staining. They produce descendants which become localized in the organizer region of the early gastrula. These cells form the prechordal plate, notochord, somites, pharyngeal endoderm and neural tube at early neurula stage. The results of extirpation of the medial two or four of these blastomeres show that the entire head lacks or the tissues and organs of the head greatly reduce. This indicates that already at the 32-cell stage they have been committed to autonomously differentiate to form the axial mesodermal tissues of the head and that their roles in the head formation can neither be replaced nor complemented by any other blastomeres surrounding them. It is also shown that the vegetal yolk cells do not seem to play essential roles for development of the axial organs of the head. On the basis of the present results a view of establishment of the organizer of Xenopus eggs is proposed.     

CARCINOMA OF THE PROSTATE—Diagnosis and Treatment

About 28 per cent of men between the ages of 71 and 75 have cancer of the prostate. Many of them do not die of the disease, but with the life span ever increasing, this problem is becoming more important.In the early stages the condition is asymptomatic; when the symptoms of urinary obstruction arise, the cancer is usually too advanced for cure. Cure depends on early diagnosis and, therefore, on routine rectal examination. The solitary hard nodule of early prostatic cancer becomes a stony hard fixed prostate as the condition progresses. X-ray and acid phosphatase studies are of help only after the cancer has metastasized. As many as 50 per cent of patients with rectally palpable early carcinoma of the prostate can be cured by radical perineal prostatectomy. Often, simple enucleation or transurethral resection is sufficient to effect cure in the case of occult carcinoma. However, some observers believe that when cancer is detected by microscopic examination of a prostate that has been removed, a radical operation should be done as soon after the initial operation as feasible. Early orchidectomy and estrogen therapy are of considerable help in slowing the process of advanced prostatic cancer and may postpone the need of transurethral resection to relieve obstruction. When these measures fail, bilateral adrenalectomy, cortisone therapy, pituitary irradiation, and pituitary extirpation have been employed, with moderate success, in an effort to diminish the androgen level.     

Postoperative radiotherapy and late mortality: evidence from the Cancer Research Campaign trial for early breast cancer.

OBJECTIVE--To identify any excess mortality caused by adjuvant radiotherapy for early breast cancer. DESIGN--Prospective randomised clinical trial. Two thousand subjects needed for study to have a 90% chance of detecting a difference in survival rate of 7% with 95% significance. Patients were followed up until June 1988, giving follow up of 158-216 months. SETTING--A multicentre trial mainly drawing patients from centres in the United Kingdom. PATIENTS--2800 Women presenting with clinical stage I or II carcinoma of the breast from June 1970 to April 1975. INTERVENTIONS--One group of women (n = 1376) had simple mastectomy followed by immediate postoperative radiotherapy (1320 to 1510 rets). The remaining women (n = 1424) had simple mastectomy with subsequent careful observation of the axilla, radiotherapy being delayed until there was obvious progression or recurrence of disease locally. END POINT--Increased mortality in patients treated with radiotherapy from causes other than breast cancer. MEASUREMENTS AND MAIN RESULTS--Survival was measured from time of first treatment to death or last follow up. Deaths from any cause and from specified causes were counted as events. Comparison over the whole follow up showed a slight excess mortality in the group treated with radiotherapy (relative risk 1.04; 95% confidence interval 0.94 to 1.15). The relative risk of death from breast cancer was 0.97 (0.87 to 1.08) but that of death from other causes was 1.37 (1.09 to 1.72), the increase mainly being in women who had had tumours of the left breast (1.61 (1.17 to 2.24)) and had been treated with orthovoltage (1.85 (1.27 to 2.71)). Analysis of causes of death after five years showed a relative risk of 2.11 (1.25 to 3.59) for new malignancies and of 1.65 (1.05 to 2.58) for cardiac disease, the increase in cardiac mortality being most pronounced in patients who had had tumours of the left breast and whose treatment had included orthovoltage radiation (relative risk 2.67 (1.28 to 5.55)). CONCLUSIONS--Adjuvant radiotherapy after simple mastectomy for early breast cancer produces a small excess late mortality from other cancers and cardiac disease. The risk has to be balanced against the higher risk of local recurrence when immediate postoperative radiotherapy is not given. The balance has to be assessed for each patient, and for many patients radiotherapy will still be desirable in the initial treatment of their early breast cancer.     

Psychiatric problems in the first year after mastectomy.

The psychiatric morbidity associated with mastectomy was assessed in 75 women by following them up from the time they presented with suspected breast cancer to one year after the operation. Fifty women with benign breast disease served as controls. Throughout the follow-up period the incidence of psychiatric problems was higher among the women who had undergone mastectomy. One year after surgery 19 (25%) of these women compared with only 5 (10%) of the controls needed treatment for anxiety or depression or both, and 16 (33%) compared with 3 (8%) respectively had moderate or severe sexual difficulties. Altogether 29 patients in the mastectomy group (39%) and six of the controls (12%) had serious anxiety, depression, or sexual difficulties. Of the eight women in the mastectomy group who sought help for their problems, only two felt that the help given had been appropriate. The inability to recognise and treat these emotional disturbances is a common and serious problem. Monitoring by specially trained nurses and social workers might help to identify them earlier and even reduce them.     

Effect of endocrine glands on the unfixed total haemocyte counts of the bug Halys dentata

Changes in total haemocyte counts in relation to the endocrine glands have been studied in Halys dentata. Unfixed total haemocyte counts were taken after extirpation and implantation of three endocrine structures. It is concluded that haemocyte count decreases after the extirpation of the corpora allata in the early life span of adults, while an abrupt increase was noted after the 7th day. When both the corpora allata and corpora cardiaca are extirpated, the count was significantly decreased throughout the life span of adults. However, when only the corpora cardiaca were removed there was no significant variation up to the 7th day, but later on the count gradually decreased. The implantation of brain, corpora cardiaca and allata is followed by a significant rise in the haemocyte count throughout the life span. Total haemocyte count also fluctuated after the implantation of corpora allata and brain, separately. After implantation of corpora cardiaca of one-day-old adult insects there was no variation in the total haemocyte count while the corpora cardiaca of 6-day-old adults when implanted in one-day-old adults cause a significant rise in the total haemocyte count. Therefore, it is concluded that the corpora cardiaca influences the total haemocyte count after a critical period.     

Tendon collagen synthesis at rest and after exercise in women.

In general, there is a higher incidence of musculoskeletal injuries during physical activity in women than in men. We hypothesized that in women rates of tendon collagen synthesis would be lower than in men at rest and after exercise, especially in the later luteal phase when estrogen and progesterone concentrations are higher than the early follicular phase. We studied tendon collagen fractional synthesis rate (FSR) in 15 young, healthy female subjects in either the early follicular (n = 8) or the late luteal phase (n = 7) 72 h after an acute bout of one-legged exercise (60 min kicking at 67% workload maximum) (72 h) and compared the results with those previously obtained for men. Samples were taken from the patellar tendon in both the exercised and rested legs to determine collagen FSR by the incorporation of [15N]proline into tendon collagen hydroxyproline. There was no effect of menstrual phase on tendon collagen synthesis either at rest or after exercise. However, there was a significant difference between women and men at rest (women = 0.025 +/- 0.002%/h, men = 0.045 +/- 0.008%/h; P < 0.05) and 72 h after exercise (women = 0.027 +/- 0.005%/h; men = 0.058 +/- 0.008%/h). Furthermore, rest and 72-h tendon collagen synthesis were not different in women, whereas in men tendon collagen synthesis remained significantly elevated 72 h after exercise. It is concluded that both in the resting state and after exercise, tendon collagen FSR is lower in women than in men, which may contribute to a lower rate of tissue repair after exercise.     

Stage at diagnosis and mortality in patients with adenocarcinoma and adenosquamous carcinoma of the uterine cervix diagnosed as a consequence of cytologic screening

OBJECTIVE: To determine if cytologic screening is associated with early stage at diagnosis of and decreased mortality from invasive adenocarcinoma and adenosquamous carcinoma of the uterine cervix. STUDY DESIGN: We retrospectively reviewed the medical records of all 169 women diagnosed with invasive adenocarcinoma or adenosquamous carcinoma of the cervix in a prepaid health plan during 1988-1994. Differences in stage and survival were assessed in relation to screening history and symptoms. RESULTS: Among the 169 cases, late-stage disease was present in 19/169 women (11.2%) at the time of diagnosis, and 24/269 (14.2%) women died of the disease during the three-year follow-up period. Women whose cancer was screen detected numbered 48/169 (28.4%) and were less likely to present with late-stage disease than non-screen-detected women: 2/48 (4.2%) versus 17/121 (14.0%) (P = .05). A mortality advantage at three years from diagnosis was associated with screen-detected cancers: 1/48 (2.1%) versus 23/121 (19.0%) (P = .002), and this advantage persisted after controlling for stage at diagnosis. CONCLUSION: Invasive adenocarcinomas and adenosquamous carcinomas of the cervix detected by screening are found at an earlier stage and are associated with lower disease-specific mortality than those not detected by screening.     

Increased risk of atherosclerosis in women after the menopause.

An increase in the incidence of cardiovascular disease has generally been observed in postmenopausal women, but there have been few studies of the association between menopausal state and atherosclerosis. In this study 294 premenopausal and 319 postmenopausal women aged 45 to 55 were examined radiographically for calcified deposits in the abdominal aorta, which have been shown to represent intimal atherosclerosis. Aortic atherosclerosis was present in eight (3%) of the premenopausal women and in 38 (12%) of the postmenopausal women. After adjustments for age and other indicators of cardiovascular risk women with a natural menopause had a 3.4 times greater risk of atherosclerosis than premenopausal women (95% confidence interval 1.2 to 9.7; p less than 0.05); women who had had a bilateral oophorectomy had a 5.5 times greater risk (1.9 to 15.8; p less than 0.005). No excess risk of atherosclerosis was observed among women who had had a hysterectomy without removal of both ovaries. These results suggest that when oestrogen production stops, either naturally or after surgery, the risk of atherosclerosis is increased.     

The role of endocrine factors in the pathogenesis of spontaneous abortion after IVF-ET

There is large body of evidence to show that the risk of early pregnancy loss is higher after IVF-ET than after natural conception. Several hypotheses have been proposed to explain this phenomenon. One of the possible etiopathogetic factors is the patient's age which is significantly higher in women undergoing IVF than in the general population of naturally conceiving women. Immunologic factors have also been suggested. It seems that procedures like ICSI do not increase the risk of spontaneous abortion (SAB) after IVF-ET. Moreover, the proportion of products of conception with chromosomal aberration in cases of SAB following ICSI procedure is not elevated. Many authors point to the problem of iatrogenic luteal defect after IVF-ET. The use of luteal support after IVF-ET is widely recommended. Interestingly, firm evidence is lacking regarding the efficacy of progestagen or hCG supplementation on the risk of SAB after IVF-ET. However the issue of the effectiveness of progesterone support in decreasing the risk of SAB after ART procedures is far from being conclusively resolved--it deserves well planned, randomized studied to be performed.     

Breast self-examination: importance of technique in early diagnosis.

Shortly after diagnosis of breast cancer 416 patients were interviewed about their use of screening procedures and the method of tumour detection. Although 72% reported that they performed breast self-examination (BSE), only 12% actually inspected and palpated their breasts monthly. BSE was not significantly associated with tumour size or involvement of the lymph nodes; however, thorough inspection was associated with smaller tumours, and careful palpation with the absence of palpable nodes. Of those who no longer or never had examined their breasts 40% reported having annual breast examinations by their physician and had significantly smaller tumours than did the others. Most of the women (86%) reported having detected their own tumours, and BSE did not significantly increase the likelihood of self-detection. The frequency of use of screening procedures was similar in a sample of women without breast cancer.     

Glucose tolerance and incidence of pancreatic islet cell antibodies in pregnancy in women with thyroid autoantibodies

The prevalence of pancreatic islet cell antibodies (ICA) and complement fixing ICA (CF-ICA) and the effect of pregnancy of glucose tolerance was studied in 3 groups of women. One group had thyroid autoantibodies in serum detected in early pregnancy and subsequent development of postpartum thyroiditis (PPT), another group had thyroid autoantibodies without signs of PPT and the third group did not have thyroid autoantibodies or PPT. In the women with thyroid autoantibodies and PPT, ICA were found in one of 12 women (8%, 95% confidence limits 0-38%). In the group with thyroid autoantibodies without PPT, ICA were found in three of 27 women (11%, 2-29%), whereas two of 20 women without thyroid autoantibodies had ICA (10%, 1-32%), N.S. Where present, serum ICA levels were very low and similar in early pregnancy and 6 months postpartum. CF-ICA were only found in two women with thyroid autoantibodies without signs of PPT. In all groups glucose tolerance was impaired in pregnancy when compared to postpartum despite an increased insulin response to glucose ingestion. In pregnancy, however, glucose tolerance was more impaired in the women with thyroid autoantibodies and subsequent PPT, than in the women without thyroid autoantibodies. Postpartum glucose tolerance was similar in all groups. It is concluded, that the presence of thyroid autoantibodies in early pregnancy or development of PPT is not accompanied by an increased prevalence of islet cell antibodies, but women with thyroid autoantibodies and subsequent PPT have a significantly more reduced glucose tolerance in late pregnancy than women without thyroid autoantibodies.     

Time since childbirth and prognosis in primary breast cancer: population based study.

OBJECTIVE: To investigate whether time since birth of last child was of prognostic importance in women with primary breast cancer. DESIGN: Retrospective cohort study based on a population based database of breast cancer diagnoses with detailed information on tumour characteristics, treatment regimens, reproductive factors, and vital status. SETTING: Denmark. SUBJECTS: 5652 women with primary breast cancer aged 45 years or less at the time of diagnosis. MAIN OUTCOME MEASURES: 5 and 10 year survival; relative risk of dying. RESULTS: Women diagnosed in the first 2 years after last childbirth had a crude 5 year survival of 58.7% and 10 year survival of 46.1% compared with 78.4% and 66.0% for women whose last childbirth was more than 2 years before their diagnosis. After adjustment for age, reproductive factors, and stage of disease (tumour size, axillary nodal status, and histological grading), a diagnosis sooner than 2 years since last childbirth was significantly associated with a poor survival (relative risk 1.58, 95% confidence interval 1.24 to 2.02) compared with women who gave birth more than 5 years previously. Further analyses showed that the effect was not modified by age at diagnosis, tumour size, and nodal status. CONCLUSIONS: A diagnosis of breast cancer less than 2 years after having given birth is associated with a particularly poor survival irrespective of the stage of disease at debut. Therefore, a recent pregnancy should be regarded as a negative prognostic factor and should be considered in counselling these patients and in the decisions regarding adjuvant treatment.     

Role of early experience in the development of preference for low-quality food in sheep

Domestic ruminant selectivity induces floristic changes in pasturelands, risking sustainability and limiting the subsequent availability of susceptible plant species. Development of preferences for species of lower nutritional quality may help to overcome those problems. In this study, we tested the hypothesis that early experience of sheep with a low-quality food (LQF) in a nutritional enriched context increases preference for LQF in adulthood. We predicted a higher proportional consumption of LQF in experienced lambs (EL) than in inexperienced lambs (IL) in choice situations involving LQF and alternative foods. Additionally, we determined intake of LQF by EL and IL at different levels of high-quality food (HQF) availability. From 60 to 210 days of age, EL were fed in separated feed bunks mature oat hay (LQF) simultaneously with sunflower meal (SM) and corn grain (CG), whereas IL were fed alfalfa hay (HQF) simultaneously with SM and CG. After exposure, EL and IL were offered LQF in free choice situations involving alternative foods, and also at five levels of HQF availability (100%, 75%, 50%, 25% and 0% of ad libitum intake). Proportional consumption of LQF was lower or similar in EL than IL. Intake of LQF was also lower or similar in EL than IL at all levels of HQF availability, except when the LQF was the only food available. Our results did not support the hypothesis that early experience with a LQF in a nutritional enriched context increases preference for LQF in adulthood. On the contrary, experience with LQF diminished subsequent preference for LQF in adulthood. It is proposed that, in the conditions of our study, continuous comparison between the LQF and the high-quality supplements (CG and SM) during the early exposure period lead to devaluation of LQF by EL through a simultaneous negative contrast effect.     

Human small breast epithelial mucin: the promise of a new breast tumor biomarker

Breast cancer remains one of the most frequently diagnosed cancers today. In developed countries, one in eight women is expected to present with breast cancer within her lifetime and an estimated 1,000,000 cases are detected each year worldwide (Canadian Cancer Statistics, http://www.cancer.ca/vgn/images/ portal/cit_86751114/14/33/1959864 11niw_stats2004_en.pdf). For women with recurrent disease, the median time of survival is about 2 years. Despite optimal surgery, adjuvant irradiation, hormonal treatment, and chemotherapy, approximately 30% of patients with localized breast cancer finally develop distant metastases. Early detection, which enables intervention at a localized and potentially curable stage, remains a central goal in breast cancer treatment. Indeed, the 5-year survival rate for women with breast cancer has been shown to increase dramatically when the disease is diagnosed at an early stage: from less than 25% in women with disseminated cancer to about 75% in patients with regional disease and over 95% in women with a localized tumor (Breast Cancer Facts and Figures, 2001-2002, http://www.cancer.org/downloads/STT/BrCaFF 2001.pdf). Unfortunately, only 60% of all breast cancers are diagnosed at a local stage. Any improvement in early detection through identification of tumor biomarkers would have a significant impact on reducing overall breast cancer mortality.