Intraoperative pressure measurement in radial artery harvest. A tool with additional value?

OBJECTIVES: The radial artery is widely used as a graft in coronary artery bypass surgery (CABG). Due to its location and function it should be screened prior to harvesting to avoid ischaemic complications of the hand. In acute situations the Allen test is often the only preoperative screening method available. As has been noted earlier, a negative Allen test does not mean a non-harvestable radial artery. We endeavoured to find out whether intraoperative pressure measurement could be used as a complement while screening the radial artery. DESIGN: Ninety patients planned for elective CABG with radial artery as a conduit were examined preoperatively with the Allen test, handheld Doppler and pletysmography of the second and fourth digits. Radial artery pressure was measured intraoperatively. Symptom scale was recorded pre- and postoperatively. RESULTS: There were ten patients with a positive Allen test. The intraoperative index of radial artery pressures was 0.868 in the Allen positive group and 0.885 in the Allen negative group with no statistically significant difference (P value .68). Tolerance of exercise and cold was significantly impaired postoperatively, P values .002 and .001 respectively. No ischaemic complications occurred. CONCLUSIONS: Intraoperative pressure measurement can be used when screening radial arteries are to be harvested and no metric preoperative screening methods are available.

Deep pericardial sling versus lateral pericardial sutures in off-pump coronary artery bypass surgery.

AIM: The aim of this study was to evaluate the safety and efficacy of deep pericardial sling (DPS) versus lateral pericardial sutures (LPSs) for heart stabilization and adequate coronary artery exposure during off-pump coronary artery bypass surgery (OPCAB). METHODS: One surgeon employed in 101 consecutive patients a series of four to six 2-0 polyglactin sutures placed laterally between the left phrenic nerve and the left pulmonary veins (LPS). Two other surgeons used in 104 consecutive patients a single 0-0 braided silk suture with moistened gauze placed in the oblique sinus of the posterior pericardium, between the inferior vena cava and the right lower pulmonary vein (DPS). RESULTS: One conversion to beating heart surgery with cardiopulmonary bypass support occurred in each study group. No patient in the LPS group was converted to DPS technique. The use of LPSs allowed a number of distal anastomoses somewhat higher than the DPS technique (4.1+/-1.1 vs. 3.7+/-1.1, P=0.02). Postoperative results were similar in both study groups. A lower incidence of postoperative low-cardiac output syndrome and of prolonged need of inotropes has been observed in the LPS group, but the difference failed to reach statistical significance. One patient in the LPS group had postoperative left phrenic nerve palsy. One patient in the DPS group suffered of intraoperative bleeding secondary to rupture of the inferior vena cava likely related to placement of DPS, which was successfully repaired. CONCLUSION: LPS technique is as effective as DPS technique and allows complete revascularization with a postoperative outcome similar to the latter technique.

Changes in natriuretic peptides, apelin and adrenomedullin after off-pump and on-pump coronary artery bypass surgery.

AIM: The authors have evaluated the postoperative changes of natriuretic peptides, apelin and adrenomedullin after off-pump (OPCAB) and on-pump coronary artery bypass surgery (CCAB) to assess the impact of these techniques on the myocardium. METHODS: Twenty-two patients underwent OPCAB and 24 patients underwent CCAB. Plasma levels of NT-proANP, NT-proBNP, apelin and adrenomedullin were measured preoperatively, and on the 1st, 3rd, and 5th postoperative day. RESULTS: Natriuretic peptides, apelin and adrenomedullin increased significantly postoperatively. Natriuretic peptides were markedly elevated on the fifth postoperative day. Apelin was still increasing, but adrenomedullin, although elevated, clearly decreased toward baseline levels on the fifth postoperative day. CCAB was associated with significantly higher postoperative cTnI, but levels of natriuretic peptides, adrenomedullin and apelin did not differ significantly after CCAB and OPCAB. cTnI, echocardiographic parameters, cardiac index, and degree of postoperative pericardial effusion did not correlate with levels of natriuretic peptides, apelin and adrenomedullin. Postoperative levels of natriuretic peptides were significantly associated with parameters of renal function, age, and extracardiac arteriopathy. The correlation between preoperative estimated glomerular filtration rate and natriuretic peptides increased along the study intervals (NT-proANP rho: -0.181, -0.350, -0.364, and -0.442; NT-proBNP rho: -0.112, -0.420, -0.405 and -0.550). Also adrenomedullin correlated with parameters of renal function. The postoperative levels of apelin were not associated with any variable. CONCLUSION: A marked, sustained and similar increase in these five markers of cardiac adaptation was detected after OPCAB and CCAB. The upregulation of these peptides should be further investigated to evaluate their potential beneficial/harmful impact on the outcome after coronary surgery.

Risk of retinal microembolism after off-pump and on-pump coronary artery bypass surgery.

AIM: In order to investigate the neuroprotective efficacy of off-pump coronary artery bypass surgery (OPCAB) over conventional on-pump coronary artery bypass surgery (CCAB), we have performed a prospective randomized study evaluating retinal circulation changes after OPCAB and CCAB. METHODS: Twenty patients were randomized to OPCAB or CCAB. Retinal fluorescein angiography and 60 degrees black-and-white as well as color fundus photographs of both eyes of each patient were taken 1 to 24 h before and 5 to 6 days after the operation. RESULTS: Patients undergoing OPCAB had more severely stenosed carotid arteries (P=0.075), higher incidence of slightly diseased ascending aorta (P=0.087) and higher Northern New England Cardiovascular Study Group stroke risk score (P=0.075). Neither stroke nor transient ischemic attack occurred postoperatively in these patients. Inferotemporal retinal arterial embolization and microinfarction was detected in one patient after CCAB, but in none of the OPCAB group. CONCLUSION: The risk of retinal embolism can be minimized by the use of OPCAB and, most likely, by adequate epiaortic ultrasound scanning of the ascending aorta and avoiding clamping in case of severely diseased aorta.

Perioperative stroke in coronary artery bypass patients.

BACKGROUND AND AIMS: Stroke has remained one of the most frustrating complications in coronary artery bypass surgery (CABG). The purpose of this study was to describe the incidence and correlates of stroke in CABG patients operated on in a hospital with low annual volume of open-heart surgery procedures. The aim was moreover to clarify subsequent outcome and self-reported satisfaction-based quality of life of patients who had experienced a stroke. MATERIAL AND METHODS: The material was a cohort of 1318 consecutive CABG patients operated on over a 6-year period. Data was collected prospectively but the final analysis was retrospective. Questionnaires supplemented the estimation of survival and subsequent functional status. RESULTS: The incidence of stroke was 2.6 %. Age > 70 years, chronic obstructive pulmonary disease (COPD), peripheral vascular disease (PVD), cerebral vascular disease (CVD), number of aortic anastomoses and significant atherosclerosis of the ascending aorta were univariate predictors of stroke. Postoperative stroke was experienced in 55.9% of cases delayed appearing from 2nd postoperative day on. Stroke patients had a higher rate of mortality (14.7% vs. 1.0%, p = 0.001) and poorer survival than no-stroke patients (82.4% and 97.4% at one year and 61.2% and 89.7% at six years, p < 0.001). CONCLUSIONS: The incidence of stroke seems to be on the same level in CABG patients from a low volume hospital as in reports from centres with a high volume of annual procedures. Stroke predicts higher mortality, longer intensive care unit (ICU) stay, longer hospitalisation and poorer survival. A relatively high number of stroke patients need permanent institutional care. Satisfaction-based quality of life in CABG patients also remains on a lower level in comparison to patients without neurological complications.

Peripheral vascular disease as predictor of outcome after coronary artery bypass grafting.

BACKGROUND AND AIMS: Understanding and objective assessment of risks is crucial in cardiac surgery. The aim of this study was to assess the influence of peripheral vascular disease (PVD) on morbidity, mortality and outcome in coronary artery bypass grafting (CABG) patients. MATERIAL AND METHODS: The ankle-brachial pressure index (ABPI) was used as indicator of PVD and was measured in 178 CABG patients. Two groups were established: 1. normal ABPI (0.9-1.3) (n = 136) and 2. lowered ABPI (< 0.9) (n = 35). The mean follow-up was 26 months. RESULTS: The presence of PVD was 20.5 %. Patients with PVD were older (p < 0.05), more often of female sex (p < 0.05), had higher Higgins's risk score (p = 0.001) and more often intermittent claudication (IC) (p < 0.001). PVD significantly predicted atrial fibrillation (FA) (p < 0.05) and relatively postoperative myocardial infarction (MI) (p = 0.058). CONCLUSIONS: The presence of PVD is relatively high in CABG patients and increases with age. PVD predicts some morbidity but seems to have fairly little influence on short-term or middle-term outcome of CABG patients. ABPI may be of only limited value in identifying patients with high operative risk in CABG.

Inhibition of atrial wall stretch-induced cardiac hormone secretion by lavendustin A, a potent tyrosine kinase inhibitor.

The cellular processes linking mechanical wall stretch to atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) secretion from the heart are unclear. In the present study, a paced perfused rat heart preparation was used to study the signaling mechanisms of atrial wall stretch-induced secretion of ANP and BNP. Vehicle or drugs were infused into the perfusate for 40 min and right atrial wall stretch was superimposed for 10 min after 25-min drug infusions by elevating the level of the pulmonary artery cannula tip. Lavendustin A, a potent inhibitor of protein tyrosine kinases, at the concentrations of 0.5 and 1.3 microM decreased atrial wall stretch-induced ANP secretion (53% and 68%, respectively, P < 0.001) in the perfused rat heart preparation, whereas no difference in the hemodynamic variables (heart rate, contractile force and perfusion pressure) were noted between groups. Lavendustin A also completely abolished the wall stretch-induced secretion of BNP. Several other protein kinase inhibitors including staurosporine (protein kinase C inhibitor), ML-9 (myosin light chain kinase inhibitor), KN-62 (Ca2+/calmodulin-dependent protein kinase II inhibitor) and H-89 (protein kinase A inhibitor) had no significant effect on atrial wall stretch-stimulated ANP secretion. In a separate series of experiments, in which the right atria were stretched for 2 h, administration of lavendustin A (1 microM) but not staurosporine (30 nM) significantly decreased sustained wall stretch-induced ANP secretion. Okadaic acid, a potent protein phosphatase A2 (PPA2) and PP1 inhibitor, at the concentration of 100 nM had no effect on basal ANP secretion but significantly accelerated the ANP secretory response to atrial wall stretch (P < 0.05). In conclusion, the findings that inhibitors of protein tyrosine kinase and protein phosphatase selectively modulated atrial wall stretch-induced ANP secretion suggest a new mechanism involving endogenous protein tyrosine activity in the regulation of natriuretic peptide exocytosis from cardiac myocytes.

Prognostic value of MMP-2 immunoreactive protein (72 kD type IV collagenase) in primary skin melanoma.

The penetration of the subepithelial basement membrane is the first critical step in the dissemination of melanoma. In vitro studies have suggested that the 72 kD type IV collagenase (MMP-2) may be important in melanoma invasion. It has recently been demonstrated that the expression of MMP-2 immunoreactive protein increased with increasing atypia in melanocytic tumours and was associated with later haematogenous metastases in melanoma. This paper investigates the value of MMP-2 as a possible prognostic marker in melanoma. The expression of MMP-2 immunoreactive protein was studied with immunoperoxidase staining in paraffin-embedded sections of 50 cases of primary skin melanoma by using specific, affinity purified antibodies. Positive immunostaining was quantified by counting the percentage of positive cancer cells and was compared with clinical patient characteristics and survival. Sixty-four per cent of the primary melanoma cases displayed positive cytoplasmic immunostaining for MMP-2 in tumour cells. Marked overexpression of MMP-2 protein (> or = 34 per cent of melanoma cells positive) correlated with the 5-year survival of the patients when compared with patients with lower MMP-2 positivity, 55 per cent vs. 85 per cent, respectively (P < 0.05). Male patients displayed positive staining more often than females (75 per cent vs. 54 per cent, respectively). There was no correlation between MMP-2 positivity and Clark level or Breslow classification. A distinct group with unfavourable prognosis was identified. The 10-year survival for MMP-2-positive male melanoma patients was 39 per cent as opposed to 79 per cent with the other melanoma patients (P < 0.05). In the hierarchic Cox regression model for survival, MMP-2 immunoreactive protein was found to be independent of Clark level and Breslow classification. Overexpression of MMP-2 protein indicated a 4.5-fold relative risk of dying from melanoma. It is concluded that MMP-2 immunoreactive protein in melanoma cells is an independent prognostic factor for survival. High MMP-2 expression in male melanoma patients indicates an unfavourable prognosis.

Mechanisms of mechanical load-induced atrial natriuretic peptide secretion: role of endothelin, nitric oxide, and angiotensin II.

There are three members in the natriuretic peptide hormone family, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP, brain natriuretic peptide), and C-type natriuretic peptide (CNP), that are involved in the regulation of blood pressure and fluid homeostasis. CNP is found principally in the central nervous system and vascular endothelial cells while ANP and BNP are cardiac hormones. ANP is synthesized mainly in the atria of the normal adult heart, while BNP is produced by both the atria and ventricles. The mechanisms controlling ANP release have been the subject of intense research, and are now fairly well understood. The major determinant of ANP secretion is myocyte stretch. Although much less is known about the factors regulating BNP release from the heart, myocyte stretch has also been reported to stimulate BNP release from both atria and ventricles. However, whether wall stretch acts directly or via factors such as endothelin- , nitric oxide, or angiotensin II liberated in response to distension has not been established. Recent studies show that by stimulating endothelin type A receptors endothelin plays an important physiological role as a mediator of acute-volume load-induced ANP secretion from atrial myocytes in conscious animals. In fact, endogenous paracrine/autocrine factors liberated in response to atrial wall stretch rather than direct stretch appears to be responsible for activation of ANP secretion in response to volume load, as evidenced by almost complete blockade of ANP secretion during combined inhibition of endothelin type A/B and angiotensin II receptors. Furthermore, under certain experimental conditions angiotensin II and nitric oxide may also exert a significant modulatory effect on stretch-activated ANP secretion. The molecular mechanisms by which endothelin-1, angiotensin II, and nitric oxide synergistically regulate stretch-activated ANP release are yet unclear.

Relaxin stimulates atrial natriuretic peptide secretion in perfused rat heart.

Relaxin, a reproductive hormone of the insulin-like growth factor family, increases heart rate in experimental animals but its other actions on cardiac function and cellular mechanisms responsible for the positive chronotrophic effect remain unknown. We have studied the actions of human recombinant gene-2 relaxin on the release of atrial natriuretic peptide (ANP) and cardiac function (heart rate, contractile force, perfusion pressure) as well as the underlying signal transduction mechanisms by using the isolated perfused spontaneously beating rat heart preparation. The administration of relaxin into the perfusion fluid at concentrations of 1.5, 3 or 10 nM for 30 min caused a dose-dependent sustained increase in heart rate, while contractile force and perfusion pressure remained unchanged. In addition, infusion of relaxin at a concentration of 10 nM into the perfusate produced a gradual 1.5-fold increase in immunoreactive ANP (IR-ANP) secretion (from 456 +/- 76 to 701 +/- 124 pg/ml, F = 4.5, P < 0.001). The ANP secretory and chronotrophic effects of relaxin appear to involve the activation of protein kinase C, since administration of a protein kinase C inhibitor staurosporine at a concentration of 30 nM completely blocked the effect of relaxin (10 nM) on IR-ANP secretion (P < 0.001) and heart rate (P < 0.001). A cAMP-dependent protein kinase inhibitor, H-89 (100 nM), also substantially reduced the ANP secretory effect of relaxin and attenuated the increase in heart rate during the sustained phase of the relaxin infusion (P < 0.001). KN-62 (3 microM), a Ca2+/calmodulin-dependent protein kinase inhibitor, decreased the positive chronotrophic effect of relaxin (P < 0.001) but did not influence significantly the effect of relaxin on IR-ANP release in isolated perfused rat heart preparation. These results provide the first evidence that relaxin stimulates the secretion of ANP from isolated perfused rat hearts. Our results also suggest that relaxin modulates ANP secretion by activation of protein kinase C and cAMP-dependent protein kinase pathways.

Stretch-induced increase in atrial natriuretic peptide secretion is blocked by thapsigargin.

The cellular mechanisms by which mechanical forces regulate myocardial function such as secretion of atrial natriuretic peptide (ANP), are uncertain. We studied the effects of thapsigargin, a specific inhibitor of sarcoplasmic reticulum Ca2+ adenosine triphosphatase, that depletes intracellular Ca2+ stores, on basal and atrial stretch-induced ANP secretion in the isolated, perfused, paced rat heart preparation. Addition of 300 nM thapsigargin into the perfusate caused gradual increase in perfusion pressure, contractile force and ANP release (P < 0.001). Thapsigargin pretreatment at concentrations (30 and 100 nM) that did not affect baseline cardiac function or hormone secretion blocked mechanical stretch-induced increase in ANP secretion. These results suggest that thapsigargin-sensitive intracellular Ca2+ pools serve as mechanotransducers in the mechanical loading-induced changes in cardiac myocytes.

Loss of heterozygosity for chromosome 11 in primary human breast tumors is associated with poor survival after metastasis.

A common feature of the malignant progression of human tumors is loss of heterozygosity (LOH) for various regions of their genomes. Such events encompassing chromosomes 11p15 and 11q23 are frequent in human breast tumors. Here, we have analyzed genetic and clinical characteristics of a series of primary breast tumors in order to determine: (a) a more finely mapped estimate of the involved regions; (b) whether there is a relationship in the presentation of LOH between the two regions; and (c) whether a correlation exists between such LOH and any of the clinical parameters pertaining to each patient. We found that LOH for 11p15.5 and 11q23 occurred in 35 and 46% of the 86 primary breast carcinomas, respectively, but in none of the 10 benign tumors examined. The minimal region of LOH for 11p15 was in the approximately 2-megabase region between loci TH and D11S988. Twenty-nine % of the tumors showed LOH simultaneously at both 11p15 and 11q23, 5% had LOH only at 11p15.5, and 15% had LOH only at 11q23. Among these genetic groups, clinical features such as tumor size, involvement of auxiliary nodes, histological subtype, tumor grade, estrogen/progesterone receptor status, and patient age were not markedly different. However, LOH of 11q23 (either alone or in conjunction with LOH of 11p15) in the primary tumor was found to be highly predictive of aggressive postmetastatic disease course with substantially reduced survival (P = 0.0004; log rank test). We also observed a slight trend toward a more rapid development of metastatic lesions, without obvious site specificity, in patients with primary tumors showing LOH for chromosome 11 in the pathogenesis of human breast cancer; we suggest that its effects are late in the progression of this disease.

Loss of heterozygosity in sporadic human breast carcinoma: a common region between 11q22 and 11q23.3.

The development of sporadic human breast cancer is associated with the accumulation of genetic alterations on several chromosomes. In the case of chromosome 11, loss of heterozygosity (LOH) at loci on the short arm has been well documented and suggests the presence of a suppressor gene(s) at 11p15.5. However, the evidence for similar events on the long arm is less compelling. Here, we determined the prevalence of LOH for chromosome 11q in 44 malignant and 3 benign cases of unselected sporadic breast tumor samples. We found that alteration of chromosome 11q is common in the pathogenesis of breast cancer as 19 of 44 (43%) malignant tumor specimens exhibited LOH. Eleven (58%) of these genetic alterations were specific to the long arm of the chromosome. The smallest region of shared LOH places the target between 11q22 and 11q23.3, the same general region frequently altered in cancers of the ovary, colon, skin, and uterine cervix, perhaps indicating the location of a tumor suppressor gene or genes of importance in each of these different tumor types.

Follicular dendritic cells have prognostic relevance in Hodgkin's disease.

The authors' previous study showed the presence of follicular dendritic cell (FDC) networks--though altered--in neoplastic areas, not only in the nodular lymphocyte predominance type, but also in other types of Hodgkin's disease. The present retrospective study was performed on 102 patients to determine whether the presence or absence of FDC networks, or parts of them, in neoplastic areas has prognostic relevance in Hodgkin's disease. Follicular dendritic cells were visualized with the monoclonal antibody Ki-FDC1P, which selectively stains FDCs in paraffin-embedded tissues. Univariate statistical analysis, in which nodular sclerosis (NS) and mixed cellularity (MC) types were combined, showed three prognostically different groups: the best prognosis was associated with nodular lymphocyte predominance cases; the worst with FDC-negative NS or MC cases; and an intermediate prognosis with FDC-positive NS or MC cases. In the NS group, the prognosis of FDC-positive cases was better than that of FDC-negative cases. After multivariate analysis, stepwise modeling identified three prognostic factors at diagnosis: stage (P = .001), FDC status (P = .001), and age (P = .06). The authors conclude that in the most common types of Hodgkin's disease (nodular lymphocyte predominance, NS, and MC), FDC status in the neoplastic area(s) bears prognostic relevance, a positive FDC status predicting a favorable prognosis and a negative FDC status an unfavorable one.

Effects of genistein on cardiac contractile force and atrial natriuretic peptide secretion in the isolated perfused rat heart.

We examined the effects of a selective protein tyrosine kinase inhibitor, the isoflavonoid genistein, on haemodynamics and atrial natriuretic peptide (ANP) secretion in perfused rat heart preparations. The addition of genistein into the perfusion fluid at concentrations of 11, 22 and 37 microM for 30 min in the spontaneously beating rat hearts caused dose-dependent, sustained increases in contractile force, perfusion pressure and immunoreactive ANP secretion, while heart rate remained constant. The positive inotropic and vasoconstrictor effects of genistein were significantly (P < 0.001) greater in the paced than in spontaneously beating rat hearts. Infusion of the calcium-channel antagonist diltiazem (3 microM) inhibited the genistein-induced positive inotropic effect by 52% (P < 0.001), and KN-62 (1.5 microM), an inhibitor of Ca2+/calmodulin-dependent protein kinase II, by 34% (P < 0.001). The genistein-induced increase in immunoreactive ANP secretion was completely blocked by diltiazem (P < 0.001) while KN-62 delayed (P < 0.02) the increase of immunoreactive ANP concentration in the perfusate. These results show that genistein, at concentrations known to inhibit the activities of protein tyrosine kinases, dose-dependently increased contractile force, coronary vascular tone and ANP secretion from isolated perfused rat hearts. These cardiac effects of genistein may be mediated by elevation of intracellular Ca2+ concentration, as shown by the inhibition of inotropic and secretory effects by both L-type calcium channel antagonist and Ca2+/calmodulin-dependent protein kinase inhibitor.

Refinement of regional loss of heterozygosity for chromosome 11p15.5 in human breast tumors.

The familial association of breast cancer with other tumors such as rhabdomyosarcoma that show loss of heterozygosity (LOH) for chromosome 11p15 as well as limited analyses showing LOH for chromosome 11p in breast tumors suggests the presence of a pleiotropic tumor suppressor gene in this region. In order to test this idea, we analyzed DNA samples for 50 matched normal and tumor tissues from unselected breast cancer patients for LOH at loci throughout the chromosome 11p15.5 region. We found that 12.5% of informative cases showed LOH at HRAS1, 26.8% at TH, and 33.3% at both D11S860 and HBB, providing genetic support for this hypothesis. In contrast to previous observations which excluded the involvement of 11p15.5 regions distal to the HBB cluster, our results indicate that the subregion between TH and HBB is a critical region in breast cancer. This region is identical to that identified for the clinically associated tumor, rhabdomyosarcoma, and thus warrants intensive molecular analysis.

Endometrial changes in postmenopausal breast cancer patients receiving tamoxifen.

OBJECTIVE: To assess the estrogenic effect of tamoxifen and associated pathologic changes of the endometrium in postmenopausal breast cancer patients. METHODS: The endometrium of 103 gynecologically asymptomatic postmenopausal breast cancer patients was examined. Fifty-one had been treated with tamoxifen and 52 had not received any hormonal treatment. The two groups were similar in age, parity, age at menopause, and body mass index. RESULTS: Compared with the control subjects, the tamoxifen patients had a thicker endometrium (mean +/- standard deviation 10.4 +/- 5.0 versus 4.2 +/- 2.7 mm; P = .0001) and larger uterine volume (45 +/- 27 versus 25 +/- 11 cm3; P = .001), as determined by transvaginal sonography. Hysteroscopy showed an atrophic endometrium in 28% of the patients in the tamoxifen group, as compared with 87% of the control patients (P = .0001). Endometrial polyps were more frequent in the tamoxifen group (36 versus 10%; P = .004), which included one patient with atypical hyperplasia, one with adenomatous hyperplasia, and one with endometrial adenocarcinoma; two controls had endometrial adenocarcinoma. CONCLUSION: The results provide evidence for an estrogenic effect of long-term tamoxifen treatment on the postmenopausal uterus and show it to be associated with an increased occurrence of polyps.

Prognostic factors in recurrent breast cancer: relationships to site of recurrence, disease-free interval, female sex steroid receptors, ploidy and histological malignancy grading.

Site of first recurrence, disease-free interval (DFI), female sex steroid receptors, ploidy measurements as well as histological grading have been analysed as potentially valuable predictive factors in 313 cases of recurrent breast cancer. Univariate and multivariate analyses show histological grading, site of recurrence and disease free interval to be useful prognostic variables when assessing prognosis once disease has recurred. High concentrations of oestrogen receptors (ER) were found in patients with bone metastases, whereas lower concentrations of ER were related to visceral recurrences. Ploidy measurements failed in this study to give any predictive information once disease recurred.

Safety and efficacy of toremifene in breast cancer patients. A phase II study.

46 postmenopausal women with estrogen receptor positive breast cancer entered a phase II study with a novel antiestrogen, toremifene. Patients had either recurrent or primarily inoperable advanced disease. No prior or concurrent cytostatic or hormonal treatment was allowed. Eight patients (17%) achieved complete response (CR), 17 (37%) partial response (PR) and 13 (28%) had stabilization of their disease at least for three months. The mean durations of responses were 52 +, 53 + and 27 + weeks, respectively, with 5 patients in CR, 6 in PR and 1 with no change (NC) still continuing the treatment. No significant differences could be seen in response rates according to the concentration of estrogen receptors or presence of progesteron receptors in this group of patients. Toxicity was not a problem, in general, the treatment was well tolerated. Two side effects (sweating and vertigo) were classified as severe and one patient after achieving PR interrupted the treatment because of tremor.