Taro flour (Colocasia esculenta) increases testosterone levels and gametogenic epithelium of Wistar rats.

This study evaluated the effects of diet containing taro flour on hormone levels and the seminiferous tubules morphology of rats. After weaning, the male rats were divided into two groups (n=12 each): control group (CG) treated with control diet and taro group (TG), fed with 25% taro flour for 90 days. Food, caloric intake, mass and body length were evaluated at experiment end. Testis followed the standard histological processing. Immunostaining was performed using an anti-vimentin antibody to identify Sertoli cells. In histomorphometry, total diameter, total area, epithelial height, luminal height and luminal area were analyzed. The testosterone levels were performed using the radioimmunoassay method. Group TG presented (P<0.05): increase in mass, body length, testicular weight, histomorphometric parameters and hormonal levels. Food intake, calorie and Sertoli cells not presented statistical differences. The taro promoted increase in the testicles parameters and hormones.

Frequency of Chlamydia trachomatis infection in cervical intraepithelial lesions and the status of cytological p16/Ki-67 dual-staining.

BACKGROUND: Chlamydia trachomatis (Ct) is not a disease subject to mandatory reporting in Brazil, and the prevalence rate of this genital infection varies according to the region in which studies are conducted, as well as by the detection technique employed. Ct has been associated with persistence of Human papillomavirus (HPV) infection and the facilitation of cervical carcinoma development. We evaluated the Chlamydia trachomatis infection and its association with cytology, p16/Ki-67 dual-stained cytology and cervical intraepithelial lesions status in a screening cohort in Brazil. METHODS: This was a cross-sectional study of 1481 cervical samples from asymptomatic women aged 18 to 64. Samples were collected for liquid-based cytology and Ct detection by polymerase chain reaction. p16/Ki-67 double staining was performed on samples with abnormal cytology. Statistical analysis was by chi-square and likelihood-ratio tests. Odds ratio (OR) and 95% confidence intervals (95% CI) were determined. RESULTS: The frequency of Ct was 15.6% and its presence was not associated with detection of p16/Ki-67 [OR = 1.35 (0.5-3.4)]. There was also no association between abnormal cervical cytology and Ct-positivity [OR = 1.21 (0.46-3.2)]. Associations were observed between p16/Ki-67 and high-grade lesions detected by cytology and in biopsies [OR = 3.55 (1.50-8.42) and OR = 19.00 (0.6-7.2), respectively]. CONCLUSIONS: The asymptomatic women in our study had a high frequency of Ct infection but this was not associated with p16/Ki-67 detection in samples with abnormal cytology. The expression of p16/Ki-67 was highest in women with high-grade CIN (p = 0.003).

Premature coronary artery calcification is associated with disease duration and bone mineral density in young female systemic lupus erythematosus patients.

Our objective was to evaluate the relevance of traditional and disease-related cardiovascular risk factors and of bone mineral density for premature coronary artery calcification in young patients with systemic lupus erythematosus. Ninety-four female patients with systemic lupus erythematosus with disease durations >5 years and <45 years were consecutively selected. Cardiovascular risks (diabetes mellitus, arterial hypertension, dyslipoproteinemia, smoking, family history, body mass index, ovarian and renal insufficiency) and systemic lupus erythematosus-related risk factors (disease duration, ACR criteria, modified SLICC/ ACR, SLEDAI and treatment) were evaluated. Bone mineral density was assessed by dual X-ray absorptiometry. Coronary artery calcification was determined by computed tomography. Coronary artery calcification was identified in 12 (12.7%) patients and was associated with a higher frequency of patients with cardiovascular risks (p = 0.001), higher number of cardiovascular risks (p = 0.002), age (p = 0.025), disease duration (p = 0.011) and SLICC (p=0.011). Individual analysis of cardiovascular risks demonstrated that menopause (p = 0.036), dyslipidemia (p = 0.003) and hypertension (p = 0.006) were significantly associated with coronary artery calcification. In addition, coronary artery calcification was associated with a lower whole body bone mineral density (p = 0.013). Multiple logistic regression analysis using cardiovascular risks, age, disease duration, SLICC and whole body bone mineral density revealed that only disease duration (p = 0.038) and whole body bone mineral density (p = 0.021) remained significant for coronary artery calcification. In conclusion, we found that disease duration and decreased bone mineral density are independent predictors for premature coronary calcification in young women with systemic lupus erythematosus, suggesting a common underlying mechanism.

Vitiligo and radiotherapy: the Koebner phenomenon demonstrated in patients with vitiligo undergoing radiotherapy for carcinoma of the breast.

We report the case histories of two patients with vitiligo who developed depigmentation of the treated skin area following radiotherapy for carcinoma of the breast. They illustrate the Koebner phenomenon, whereby depigmentation occurs as a trauma response in patients with vitiligo.

The Christie Hospital breast conservation trial: an update at 8 years from inception.

In 1990, we published the results of a clinical trial involving 708 patients with breast carcinoma of 4 cm or less in diameter, who, following lumpectomy, were randomized to have radiotherapy to the tumour bed only (limited field, LF group) or to the whole breast and regional nodes (wide field, WF group). No adjuvant systemic therapy was prescribed. At the time the median follow-up was 37 months. We present the updated results after an extended median follow-up of 65 months. The overall survival is 72.7% and 71.2% for the LF and WF groups respectively. The actuarial breast recurrence rate (first event) is 15% (LF) versus 11% (WF) for infiltrating ductal carcinoma, whereas, for infiltrating lobular carcinoma, the recurrence rate was 34% (LF) versus 8% (WF). A high actual recurrence rate of 21% (LF) and 14% (WF) was also found for extensive ductal carcinoma in situ. It was extremely rare for medullary, mucoid or tubular carcinomas to recur. Salvage surgery was possible in 86% (LF) and 90% (WF) respectively. The recurrence rate in the breast following lumpectomy and wide field irradiation is comparable with others reported in the literature. This trial also shows the lumpectomy with limited field irradiation is feasible, albeit with a higher breast recurrence rate; the latter could be reduced by improved selection and refinement of the technique.

Use of an electron beam for post-mastectomy radiotherapy: 5-year follow-up of 500 cases.

Since 1982, the standard method of postmastectomy regional radiotherapy at the Christie Hospital has been to use a single electron field of fixed energy (8 MeV) to irradiate the chest wall, matched to a single megavoltage field (4 or 8 MV) irradiating the nodal areas in the axilla and supraclavicular fossa. (A separate parasternal field was not used.) All 500 cases treated in 1982 and 1983 with this method were reviewed (median follow-up 59 months). Four hundred and twenty-two were referred directly post-mastectomy and 78 for local recurrence after previous mastectomy. Of these, 42 were treated palliatively, and 458 with radical intent. In radical cases the given dose in both fields was 40 Gy in 15 fractions in 3 weeks. The overall survival (n = 458) was 51% (actuarial) at 5 years. At 5 years the local recurrence rate by site and UICC stage were as follows: chest wall - all Stages 17%, Stage I 4%, Stage II 13%, Stage III 26%, recurrent cases 21%; axillary recurrence - all Stages 20%, Stage I 4%, Stage II 10%, Stage III 22%, recurrent cases 39%; supraclavicular recurrences - all Stages 9%. Only one patient of the 500 treated had a parasternal recurrence. Late effects included mild telangiectasia in the electron field and asymptomatic apical lung fibrosis in the photon field. There was no match line fibrosis.

Conservation of the breast using two different radiotherapy techniques: interim report of a clinical trial.

Patients with a clinically palpable breast carcinoma, 4 cm or less in diameter, and with no palpable nodes in the axilla were prospectively entered into a randomized clinical trial. A total of 713 patients were registered between November 1982 and December 1987, of whom 708 are evaluable at a median follow-up of 37 months. Following excision of the primary tumour, patients were randomly allocated either to have radiotherapy to the affected quadrant only (LF group) or to the whole breast and regional lymph node areas (WF group). No adjuvant hormone or chemotherapy was prescribed. The primary tumour was reported as completely excised histologically in 80% of cases, incompletely excised in 10%, and no estimate was possible in 10%. At six years from first randomization, 96% of the WF group and 92% of the LF group have remained free of breast recurrence (94% and 87% actuarial breast recurrence-free survival at 5 years). Part of the difference may be explained by the 20% recurrence rate in the breast for lobular carcinomas treated within the LF group. Of the WF group 14 patients (4%) developed recurrent disease in the axilla, compared to 50 patients (14%) in the LF group (95% and 86% actuarial axillary recurrent-free survival at 5 years). Patients with primary tumours histologically 1 cm or less in diameter had a 98% actuarial 5-year survival compared with 74% for those with tumours measuring 2 cm or more in diameter (P = 0.003). Continued follow-up of these patients will provide further information on the factors governing local/regional recurrence.

Mortality patterns over 34 years of breast cancer patients in a clinical trial of post-operative radiotherapy.

Between January 1949 and June 1955 a clinical trial was held in which patients with operable breast carcinoma were subjected to a radical mastectomy and then randomised to either have immediate post-operative radiotherapy (radiated group) or delayed radiotherapy on recurrence (watched group). Data relating to the 1461 patients entered in the trial have been analysed to investigate the late effects of treatment, if any, over a period of 34 years. A logrank comparison of the survival patterns of the radiated and watched groups, considering all deaths, during the first 15 years of follow-up did not show any statistically significant difference (P = 0.37). However, after 15 years there was a significantly increased mortality in the radiated group (P = 0.0025). The relative risk after 15 years for the radiated group relative to the watched group was 1.43 with a 95% confidence interval of 1.13 to 1.81. Taking the series as a whole, this increased mortality was attributable to deaths from cardiovascular disease (excluding cerebrovascular disease). There was no evidence that the increased mortality due to cardiovascular disease was significantly different between patients who had a left- or right-sided tumour. There was also no significant difference between the watched and radiated group from mortality due to breast cancer or other malignancies. The data analysed here relate to patients treated 40 years ago. Neither the type of surgery nor the techniques and quality of radiation are used any longer. Furthermore, an artificial radiation menopause has also fallen into disuse. Data should be prospectively gathered from more recent trials, to see if there is any hazard in the very long term from present day methods of treatment. These should include patients treated by lesser forms of surgery, supervoltage therapy, adjuvant hormone and/or chemotherapy.

Thirty-four year follow up of patients with breast cancer in clinical trial of postoperative radiotherapy.

An extended follow up to a maximum of 34 years was carried out on a series of 1461 patients who had been entered into a randomised clinical trial comparing immediate postoperative radiotherapy (treated group) with an optional delayed radiotherapy policy (watched group) after Halsted radical mastectomy for operable breast cancer. Long term survival was compared separately in patients with negative and positive axillary nodes and in two periods when different techniques of radiotherapy were used. No significant differences were noted in survival overall or in any subgroup. In patients with negative axillary nodes treated in the earlier period when the "quadrate" radiotherapy technique was used, however, the difference in survival was of borderline significance (p = 0.052), to the benefit of the watched group. Because of the large numbers of patients entered and the long follow up any possible harmful or beneficial effect of immediate postoperative radiotherapy would have been apparent in the results of this trial. The absence of any such effect implies that postoperative radiotherapy given to prevent or delay local recurrence of breast cancer is unlikely to be associated with a detectable effect on survival.

A clinical assessment of loading dose tamoxifen for advanced breast carcinoma.

Seventy patients with advanced breast carcinoma were treated with a loading dose regimen of 160 mg Tamoxifen on day 1 followed by a maintenance dose of 20 mg daily from day 2 onwards. Compliance was 100% and only 3 patients developed mild side effects. In 27% regression of disease was observed within 1 month and in 57% within 2 months. This regimen is recommended for routine clinical use.

Tamoxifen in the treatment of male breast carcinoma.

Twenty-four patients with advanced carcinoma of the male breast have been treated with tamoxifen citrate (Nolvadex). An objective regression rate of 37.5% was obtained, with five complete and four partial responses. In addition, two patients had stabilisation of their disease for 24 months each. Regression of disease was noted in soft-tissue disease, bone and lung metastases. The duration of response ranged from 8 months to 60 months with a mean of 21 months. In view of the singular lack of side-effects and the age group of the patients (mean age 63 years), it is suggested that tamoxifen should be the first line of endocrine therapy before orchidectomy or adrenalectomy.

Variation of receptor status in cancer of the breast.

One hundred and nineteen patients with breast cancer had 2 or more lesions removed for oestrogen (REc) or progesterone receptor (RPc) assay, either synchronously (on 38 occasions) or after an interval (on 91 occasions). In all but 7 both receptors were assayed for each lesion. The assays did not agree on the presence or absence of REc alone, RPc alone or the combination of both receptors in 11, 13 and 16% respectively of the synchronous samples, compared with 23, 30 and 43% of the asynchronous samples. The differences between the synchronous and asynchronous samples were significant for the combined receptors (P = 0.007) but not for REc (P = 0.176) or RPc alone (P = 0.077). Variation between asynchronous biopsies was greater when the earlier lesion contained RPc (18/37 disagreed) than when it did not (8/50) disagreed, P = 0.0023). This was not true for oestrogen receptor. In those remaining receptor positive there was only a weak correlation between the first and second values (Spearman rank correlation coefficient, rho = 0.39 for REc, P less than 0.02, and 0.45 for RPc, 0.05 less than P less than 0.1). Receptor levels and receptor status may change with time. Biopsy is most appropriate at the time when systemic treatment is proposed.

Trilostane in the treatment of advanced breast cancer.

The combination of trilostane 960 mg daily and either dexamethasone 0.5 mg b.d. or hydrocortisone 10 mg b.d. has been used to treat advanced metastatic breast cancer in post-menopausal women. Twenty-three patients had assessable disease and received treatment for a minimum of 8 weeks. Six (26%) showed an objective response and three (13%), stabilisation of previously progressive disease, sustained for at least 3 months. Side-effects were mainly gastrointestinal. Biochemical studies suggest that the mechanism of action may be inhibition of conversion of androstenedione to oestrone.

The prognosis of breast carcinoma in women aged less than 40 years.

A retrospective analysis has been carried out on 803 patients with breast carcinoma and aged less than 40 years. All the patients were followed up at the Christie Hospital for a maximum for 15 years. The survival for the whole group was 52% at five years, 40% at 10 years and 33% at 15 years. In this study for worsened with decreasing age. When the axillary nodes were involved, the five-year survival for patients aged 30 years and younger was only 34% compared to 51% in the 31-35 year group and 57% in the 36-39 year group. At 15 years the comparable figures were 18, 28 and 38% (P = 0.0001).

The clinical value of multiple steroid receptor assays in breast cancer management.

Measurement of cytoplasmic estrogen (REc) and progesterone (RPc) receptors in human breast tumors together with estrogen receptor activity in the residual pellet ("nuclear" REN) provides a more accurate prediction of hormonal dependence that REc alone. Of 74 patients with advanced metastatic breast cancer, 57% of those with REc+ tumors had an objective response to endocrine manipulation. Of 51 patients whose tumor was assayed for both REc and RPc activity, 9 of 12 patients with REc+ RPc+ tumors showed remission, whereas only 3 of 30 patients with REc- RPc-, 2 of 6 with REc+ RPc-, and 2 of 3 with REc- RPc+ tumors had a clinical response. In a group of 19 patients where triple assay was performed, 5 of 6 with tumors positive for all three receptors responded, whereas 9 patients with triple negative tumors all showed no remission. Fifty-nine percent of primary and 60% of metastatic tumors with REc+ activity were also shown to be RPc+. Thirteen percent of REc- tumors were RPc+. Patients with REc+ RPc+ primary tumors tended to have a longer disease-free interval than patients with RPc- tumors, irrespective of whether the tumors were REc+ or REc-. In the light of the possibility of employing receptor status of the primary tumor to predict hormonal responsiveness in subsequent recurrences, a comparison is made of receptor status measured in primary tumors and metastases.

Triple hormone-receptor assay: a more accurate predictive tool for the treatment of advanced breast cancer?

In a group of 74 patients with advanced metastatic breast cancer, 57% of those with cytoplasmic oestrogen receptor activity in their tumours (REC+) showed a clinical response to endocrine therapy. Of 51 patients whose tumour was assayed for both REC and cytoplasmic progesterone (RPC) activity, 9/12 patients with REC+ RPC+ tumours responded to hormone treatment, whereas only 3/30 patients with REC-RPC-tumours had a clinical response. In a group of 19 patients in whom nuclear oestrogen receptor (REN) was also estimated in the pellets from tumour-tissue homogenates, 5/6 with tumours positive for all 3 receptors showed a clinical response. None of the 9 patients with triply negative tumours responded. Addition of the REN assay appears to reinforce the greater precision of prediction when RPC as well as REC are estimated in breast tumours.