Is clinical breast examination important for breast cancer detection?

BACKGROUND: Screening clinical breast examination (cbe) is controversial; the use of cbe is declining not only as a screening tool, but also as a diagnostic tool. In the present study, we aimed to assess the value of cbe in breast cancer detection in a tertiary care centre for breast diseases. METHODS: This retrospective study of all breast cancers diagnosed between July 1999 and December 2010 at our centre categorized cases according to the mean of detection (cbe, mammography, or both). A cbe was considered "abnormal" in the presence of a mass, nipple discharge, skin or nipple retraction, edema, erythema, peau d'orange, or ulcers. RESULTS: During the study period, a complete dataset was available for 6333 treated primary breast cancers. Cancer types were ductal carcinoma in situ (15.3%), invasive ductal carcinoma (75.7%), invasive lobular carcinoma (9.0%), or others (2.2%). Of the 6333 cancers, 36.5% (n = 2312) were detected by mammography alone, 54.8% (n = 3470) by mammography and cbe, and 8.7% (n = 551) by physician-performed cbe alone (or 5.3% if considering ultrasonography). Invasive tumours diagnosed by cbe alone were more often triple-negative, her2-positive, node-positive, and larger than those diagnosed by mammography alone (p < 0.05). CONCLUSIONS: A significant number of cancers would have been missed if cbe had not been performed. Compared with cancers detected by mammography alone, those detected by cbe had more aggressive features. Clinical breast examination is a very low-cost test that could improve the detection of breast cancer and could prompt breast ultrasonography in the case of a negative mammogram.

Influence of postangioplasty beta-irradiation on endothelial function in porcine coronary arteries.

BACKGROUND: Postangioplasty (PTCA) intracoronary radiation therapy (ICRT) has been demonstrated to limit restenosis. The consequences of these procedures on coronary reactivity are unknown. METHODS AND RESULTS: Porcine coronary arteries were studied after PTCA immediately (n=5) and 6 weeks (n=5) after ICRT (n=5 and 5, respectively), after combined PTCA+ICRT (n=5 and 7, respectively), and after no intervention (n=11). A 3-cm-long source train of Sr/Y(90) was used in vivo to deliver 16 Gy at a depth of 2 mm from the source center, as used in clinical trials. Arterial rings were mounted on myographs to record isometric tension. After achieving steady-state contraction to depolarizing physiological solution containing 40 mmol/L KCl, measured baseline tension was significantly elevated immediately after all interventions. It returned to normal levels 6 weeks after PTCA and ICRT alone but was significantly reduced if combined. Active contractions induced by 40 mmol/L KCl were maintained after combined therapy both immediately after and at 6 weeks. In these depolarizing conditions, nitric oxide-dependent relaxation to substance P was trivial after PTCA+ICRT and reduced after ICRT, whereas in the presence of physiological solution and N(omega)-nitro-L-arginine, substance P-induced relaxation was reduced after PTCA and abolished after PTCA+ICRT 6 weeks after intervention. In rings without endothelium, the relaxation mediated by sodium nitroprusside (0.1 micromol/L) was reduced immediately after PTCA and at 6 weeks. CONCLUSIONS: PTCA+ICRT altered the passive mechanical properties of porcine coronary arterial wall. Furthermore, at 6 weeks, receptor-operated release of endothelium-derived nitric oxide and endothelium-derived hyperpolarizing factor was reduced by ICRT and PTCA alone, respectively, and was prevented by their combination.

Randomized trial comparing intravenous nitroglycerin and heparin for treatment of unstable angina secondary to restenosis after coronary artery angioplasty.

BACKGROUND: The treatment of unstable angina targets the specific pathophysiological thrombotic process at the site of the active culprit lesion. In unstable angina due to a restenotic lesion, smooth muscle cell proliferation and increased vasoreactivity may play a more important role than thrombus formation. Therefore, the relative benefits of nitroglycerin and heparin might differ in unstable angina associated with restenosis compared with classic unstable angina. METHODS AND RESULTS: We randomized 200 patients hospitalized for unstable angina within 6 months after angioplasty (excluding those with intracoronary stents) to double-blind administration of intravenous nitroglycerin, heparin, their combination, or placebo for 63+/-30 hours. Recurrent angina occurred in 75% of patients in the placebo and heparin-alone groups, compared with 42.6% of patients in the nitroglycerin-alone group and 41.7% of patients in the nitroglycerin-plus-heparin group (P<0.003). Refractory angina requiring angiography occurred in 22.9%, 29.2%, 4. 3%, and 4.2% of patients, respectively (P<0.002). The odds ratios for being event free were 0.24 (95% CI, -0.13 to 0.45, P=0.0001) for nitroglycerin versus no nitroglycerin and 0.98 (95% CI, -0.55 to 1. 73, P=NS) for heparin versus no heparin. No patient died or suffered myocardial infarction. CONCLUSIONS: Intravenous nitroglycerin is highly effective in preventing adverse ischemic events (recurrent or refractory angina) in patients with unstable angina secondary to restenosis, whereas heparin has no effect.

Effects of diltiazem, dipyridamole, and their combination on hemostasis.

Calcium channel blockers and antiplatelet agents, alone and in combination, have been reported to induce bleeding in patients undergoing surgery. Since diltiazem and dipyridamole influence platelet function in vitro and in vivo, their influence on hemostasis was examined in five normal men given diltiazem, 90 mg by mouth, followed by 60 mg every 6 hr for 48 hr, or dipyridamole, 75 mg by mouth every 8 hr for 48 hr. At 24 hr, the alternate drug was added to the regimen to assess effects of the combination on hemostasis. Platelet aggregation, serum thromboxane B2 and 6-keto-PGF1 alpha concentrations (stable metabolites of thromboxane A2 and prostacyclin), bleeding time, prothrombin time, partial thromboplastin time, and serum diltiazem concentrations were measured. Diltiazem and dipyridamole alone and in combination had no significant effect on bleeding time, prothrombin time, or partial thromboplastin time. Platelet aggregation induced by threshold concentrations of adenosine diphosphate, epinephrine, and calcium ionophore A 23187 were inhibited by diltiazem and dipyridamole alone and in combination. The only change in prostaglandin concentrations was a slight increase in serum 6-keto-PGF1 alpha after diltiazem. Despite influences on platelet function, neither diltiazem nor dipyridamole alone or in combination induced clinically relevant changes in hemostasis.

Hemodynamic effects of nitroglycerin combined with diltiazem in patients with coronary artery disease.

Resting coronary and left ventricular hemodynamic effects of diltiazem and nitroglycerin, given intravenously in combination, were studied in 12 patients with coronary heart disease. Results observed with this combination were compared with those in seven patients given diltiazem initially (group I) and five patients given nitroglycerin initially (group II). The diltiazem-nitroglycerin combination reduced systolic blood pressure 27 percent (p less than or equal to 0.05) with no significant change in heart rate to affect a 22 percent (p less than or equal to 0.05) decrease in the rate-pressure product. Left ventricular end-diastolic pressure (-36 percent) and dp/dt (-6.4 percent) both declined (p less than or equal to 0.05). Coronary flow and cardiac output were both maintained. Diltiazem alone and nitroglycerin alone also reduced systolic pressure and the rate-pressure product but to a lesser degree than the combination. Diltiazem did not significantly affect left ventricular end-diastolic pressure and dp/dt. Nitroglycerin reduced left ventricular end-diastolic pressure to an extent similar to the reduction produced by the combination but increased heart rate whereas this determinant of myocardial oxygen demand did not increase significantly with the combination. These findings suggest that the combination of diltiazem and nitroglycerin produces a greater reduction in myocardial oxygen demand than either drug alone. In addition, the combination maintains coronary blood flow without increases in determinants of myocardial oxygen demand. This potentially beneficial drug combination warrants further trial in patients with myocardial ischemia.

Effect of nitroglycerin on coronary collateral flow and pressure during acute coronary occlusion.

Coronary collateral function was evaluated in 21 conscious, unsedated patients by measuring aortic and distal coronary pressures and great cardiac vein flow during transient (1 minute) balloon occlusion of the anterior descending artery in the course of coronary angioplasty. Measurements were made before and during administration of intravenous nitroglycerin (NTG). Clinical, electrocardiographic and hemodynamic events of transient myocardial ischemia occurred in 10 patients before and 6 patients during NTG administration (p = 0.11). The NTG infusion consistently decreased pressure determinants of myocardial oxygen demand without increasing heart rate. NTG also decreased a calculated coronary collateral resistance index in 13 patients. Responsiveness to NTG did not appear to depend on the presence or absence of collateral vessels detected by angiography or on any other angiographic variable assessed. Measurement of coronary collateral function during coronary angioplasty is a new technique with the potential to assess the ability of interventions to prevent transient myocardial ischemia and improve myocardial perfusion during acute coronary occlusion in humans.

Effects of diltiazem during tachycardia-induced angina pectoris.

To investigate the mechanism of relief of angina pectoris by diltiazem administration, 14 patients with effort angina were studied using a protocol to control heart rate. Coronary, systemic and left ventricular (LV) hemodynamic function was assessed at rest and during tachycardia stress (atrial pacing)-induced angina before and during diltiazem infusion. Angina occurred in all patients during tachycardia stress before diltiazem administration. During tachycardia stress at the heart rate that produced angina after diltiazem infusion, pressure-rate product, coronary sinus flow and resistance and ST-segment depression were all similar to findings before diltiazem. Although at the onset of angina, systolic pressure was usually slightly lower after diltiazem infusion (138 +/- 11 vs 128 +/- 11 mm Hg, p less than 0.05), the pacing rate at onset of angina was higher in only 3 patients and the pressure-rate product was higher in only 1 patient. After diltiazem, left ventricular end-diastolic pressure increased less frequently after interruption of pacing. The results suggest that diltiazem favorably alters the relation between myocardial oxygen demand and supply at rest, but during tachycardia, anginal threshold and coronary reserve do not change. Diltiazem's potent antianginal action, shown in previous investigations using exercise-induced angina, is not prominent when heart rate is controlled. The major benefit of diltiazem in patients with stress-induced angina is related to reduction of myocardial oxygen demand rather than improved myocardial oxygen delivery.

Systemic, left ventricular and coronary hemodynamic effects of intravenous diltiazem in coronary artery disease.

Systemic and coronary hemodynamic effects of intravenous diltiazem, administered as a bolus of 250 micrograms/kg followed by an infusion of 1.4 micrograms/kg/min, were examined in 14 patients with effort angina. There was no change in heart rate despite significant decreases in systolic, diastolic and mean systemic pressures (13%, 10% and 11%, respectively, all p less than 0.01). The blood pressure decrease was closely correlated with the initial blood pressure (r = 0.81, p less than 0.05). Neither left ventricular end-diastolic pressure nor peak dP/dt changed significantly, but peripheral vascular resistance decreased 16% (p less than 0.001) and stroke volume index increased 10% (p less than 0.05). The pressure-rate product decreased 15% (p less than 0.005), but coronary blood flow was maintained as coronary resistance decreased 14% (p less than 0.025). Diltiazem increased regional coronary flow in some patients. Thus, intravenous diltiazem dilates coronary and systemic resistance vessels, without an increase in heart rate, favorably altering indexes of myocardial oxygen supply and demand.

Predictive factors of restenosis after multivessel percutaneous transluminal coronary angioplasty.

To evaluate the rate and predictive factors of restenosis after multivessel percutaneous transluminal coronary angioplasty (PTCA), 122 consecutive patients with multivessel PTCA performed in the same setting were included in a prospective study. Systematic angiographic control at 6 months was performed in 112 patients (92%). Restenosis (increase > 20% and stenosis > 50%) was found in 62 patients (55%) and 82 of 254 segments (32%) were dilated. Statistical analysis identified the number of successfully dilated segments as the only predictor of restenosis by patient (2.4 +/- 0.7 vs 2.0 +/- 0.7; p < 0.03), and the greater degree of residual stenosis as the only predictor of restenosis by lesion (30 +/- 14% vs 23 +/- 12%; p < 0.005). Twenty-two of 62 restenosed patients (35%) were asymptomatic (group 1). Baseline clinical and angiographic characteristics of these patients were similar to those with symptomatic restenosis (n = 40; group 2) and without restenosis (n = 50; group 3). Repeat revascularization for restenosis was used only in symptomatic patients (re-PTCA in 36; bypass surgery in 4). After a mean follow-up of 75 +/- 24 months, clinical status, and rates of cardiac death and myocardial infarction were similar in the 3 groups. Medical care was similar in groups 1 and 3, and higher in group 2. However, the rate of repeat revascularization for progression of disease was similar in the 3 groups (29%). In conclusion, restenosis is a frequent event after multivessel PTCA and is strongly related to the number of successfully dilated segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Inability of caliper measurement to enhance observer agreement in the interpretation of coronary cineangiograms.

Important clinical decisions are made on the basis of the interpretation of the degree of stenosis in the coronary cineangiogram. Thus, minimization of observer variation (both intra and inter) is crucial. The purpose of this investigation was to determine if measurement of stenotic lesions by caliper (CM) as compared with the usual eyeball method (EM) would reduce observer variation. Five observers, using the AHA scoring system, estimated maximal luminal narrowing in 14 segments on 10 films providing 2 reports on each film by EM and 2 by CM, thus making observations on 2800 segments. This allowed analysis of intraobserver variation for each reporter for method EM and CM, and for interobserver variation by each method. Since chance agreement is an important component in an observational study, a correction for this was made using the Kappa statistic. The results revealed that the mean Kappa by EM was 0.71 compared to 0.63 by CM (1 being perfect agreement and 0 no agreement). Agreement was much greater in proximal rather than distal segments. Interobserver agreement was consistently higher by EM K = 0.62 than CM K = 0.53 (p = 0.0007). A delineation of the types of disagreement and their clinical significance are important considerations in the evaluation of observer variation. It is concluded that the use of a caliper does not enhance either intra or interobserver agreement.

Treatment of long, diffuse, in-stent restenotic lesions with beta radiation using strontium 90 and sequential positioning "pullback" technique: procedural details and clinical outcomes.

BACKGROUND: Long, diffuse, in-stent restenotic lesions have been problematic for many patients, necessitating the need for multiple repeat percutaneous coronary interventions (PCI). The need for repeat PCI has been significantly reduced in patients since the advent of vascular brachytherapy. In-stent restenosis resulting in long lesions (> 30 mm) presents even more of a challenge. The interventional injury length created during PCI is usually greater than 30 mm and the vascular brachytherapy systems available in most hospitals are 30 mm or 40 mm in length. The purpose of this paper is to define "pullback technique" and to report the Montreal Heart Institute (MHI) data to show that the pullback technique using the Novoste system seems to be a safe and effective method for using vascular brachytherapy to treat long, diffuse, in-stent restenotic lesions. METHODS: We reviewed the database of patients enrolled in the Compassionate Use Registry between August 1999 and July 2000. The data are reported on 23 consecutive patients treated with the pullback technique. RESULTS: The mean lesion length was 49.4 +/- 19.8 mm. Three patients (13%) underwent target vessel revascularization. Angiographic follow-up was obtained in 18 patients (78%). Seven patients (38.8%) showed angiographic restenosis (> 50% luminal re-narrowing). No aneurysms or zones of ectasia were noted. CONCLUSION: This angiographic and clinical evaluation of the MHI Compassionate Use Registry data show the pullback technique to be safe from both a dosimetric and clinical point of view.

Angioscopic evaluation of thrombus removal by the POSSIS AngioJet thrombectomy catheter.

Coronary angioplasty in a thombotic vein graft is associated with a low success rate and a high risk of periprocedural complications. The aspiration thrombectomy catheter is a new device designed to treat such cases. We report a first angioscopic description of thrombus removal by the AngioJet thrombectomy catheter.

Pharmacodynamic aspects of intravenous diltiazem administration.

The diltiazem serum concentration and the magnitude and time course of systemic and coronary hemodynamic and ECG responses to intravenous diltiazem (250 micrograms/kg intravenous bolus plus 1.4 micrograms/kg/min infusion) were investigated in 14 patients with chronic stable angina pectoris. After 3, 8, and 15 minutes this dosing schedule produced serum concentrations of 570 +/- 259, 199 +/- 62, and 136 +/- 30 ng/ml, respectively (mean +/- SD). These drug levels were associated with a small, transient increase in heart rate (6 bpm, mean) at 3 minutes, which occurred during the nadir of the blood pressure response. But at 8 and 15 minutes, heart rate was unchanged compared to control rates, although blood pressure remained decreased (19%, p less than 0.01 at 15 minutes). Pressure-rate product was significantly reduced as left ventricular end-diastolic pressure and dP/dT remained unchanged. Systemic resistance decreased 17% (p less than 0.05) and stroke index increased 10% (p less than 0.01). Coronary flow was maintained as coronary resistance declined (14%, p less than 0.01). PR interval prolongation (14%, p less than 0.01) occurred at 15 minutes. Correlations between changes in systolic, diastolic, and mean pressures and drug concentration were significant (r = -0.59, -0.80, and -0.78, respectively, all p less than 0.05). The intercept for each regression line was approximately 96 ng/ml diltiazem concentration, suggesting that this represents the minimum effective diltiazem serum concentration. These results indicate that intravenous diltiazem is well tolerated and promptly reduces blood pressure and both systemic and coronary resistances without oxygen-wasting effects of an increase in heart rate.

Assessment of left ventricular function using digital angiography.

We have demonstrated that selective digital left ventricular angiography using small amounts of contrast material minimized both symptoms and hemodynamic alterations and provided good images for assessment of regional ventricular function. However, comparisons of ejection fraction (EF), end-systolic volume (ESV), and end-diastolic volume (EDV) from digital angiography, at 10 frames per second, with measurements derived from conventional angiography, showed only a fair correlation between the two methods. Using a new generation of digital equipment and an acquisition time of 30 frames per second, we studied the correlation between digital and conventional angiography in 29 patients with coronary artery disease for a wide spectrum of left ventricular functions. Ventricular volumes and EF were calculated by computer using the area-length method. The correlation coefficient (r) between both the methods was 0.93 for EF, 0.95 for ESV and 0.89 for EDV. Thus digital left ventricular angiography provides an accurate evaluation of left ventricular function and can with advantage replace conventional angiography for this purpose.

Systemic and coronary hemodynamic effects of combined intravenous diltiazem and nitroglycerin administration.

This study evaluated left ventricular (LV) and coronary hemodynamic effects of intravenous nitroglycerin (NTG) in the presence of an intravenous infusion of diltiazem in 15 patients with severe coronary disease. Diltiazem (250 microgram/kg bolus followed by 1.4 micrograms/kg/min infusion) alone decreased mean systemic blood pressure (mean 6%) without changing heart rate or LV end-diastolic pressure. The rate of rise in LV pressure declined slightly (4%), and peripheral resistance decreased (19%). Coronary sinus (CS) and great cardiac vein (GCV) flows were preserved. Addition of NTG (average, 68 micrograms/min) decreased systemic pressure further (7%) as LV end-diastolic pressure declined (5 mm Hg). These pressure changes were accompanied by a 10% increase in heart rate (compared with the heart rate found with diltiazem alone). Peripheral resistance was similar to values after diltiazem alone. The CS and GCV flows did not decrease. The sequence of intravenous drug administration was reversed in three other patients with combination therapy, producing similar effects, regardless of which drug was administered first. Hemodynamic effects of intravenous diltiazem alone and its combination with intravenous NTG seemed potentially favorable for patients with ischemic heart disease.

Management of resistant coronary lesions by the cutting balloon catheter: initial experience.

Resistant coronary lesions remain a challenge for modern angioplasty. Classical approaches include high-pressure inflations, prolonged inflations, or balloon oversizing. More recently, new technologies like rotablator, atherectomy, or laser have been proposed as adjunct to balloon angioplasty for the treatment of these specific lesions. However, all these technologies remain more difficult to handle, costly, and they do not offer long-term benefit over conventional methods. Therefore, a simple device such as the cutting balloon catheter which has been developed from a standard over the wire balloon catheter, may prove to be useful in resistant coronary lesions. We present our single center experience using the new cutting balloon catheter in six resistant lesions.

Usefulness of digital subtraction left ventriculography in patients with ischemic heart disease: comparison with cineangiography.

Digital subtraction and computer enhancement of left ventriculography allow the injection of small amounts of contrast medium into the left ventricle. Image quality measurements of cardiac volumes, and ejection fraction and evaluation of regional wall motion were compared following digital subtraction and cine ventriculography in 30 patients undergoing coronary arteriography for suspected or proven ischemic heart disease. At concentrations of 13% to 19% (iodine contents: 2.0 to 5.0 g) meglumine sodium diatrizoate used for digital subtraction ventriculography, no alterations of ventricular pressures were noted; premature ventricular contraction and cineventriculography in 30 patients undergoing coronary arteriography for suspected wall motion by two independent observers showed complete agreement between digital and cineventriculography in 141 of 150 segments (94%), including 114 normal segments; digital ventriculography led to underestimation of four segments and to overestimation of five. Left ventricular ejection fraction and volumes calculated using both techniques correlated relatively well (ejection fraction: r = 0.86; end systolic volume: r = 0.88; end diastolic volume: r = 0.665). Thus, intraventricular injection of low concentrations of contrast medium provides good digital angiographic images and may eventually replace cine ventriculography for invasive assessment of left ventricular performance. However, ECG gating and shorter exposure times will be required for accurate measurement of ventricular volumes and ejection fractions.

Design features of a controlled clinical trial to assess the effect of a calcium entry blocker upon the progression of coronary artery disease.

This report presents the design and methodological features of a double-blind, randomized, placebo-controlled, trial in 383 patients with coronary artery disease. The study's principal objective is to determine whether chronic treatment with a calcium entry blocker can retard the progression of coronary artery disease. The study population consists of patients with coronary artery disease and a baseline coronary arteriogram that qualifies them as being at high risk for disease progression. After satisfying all entry criteria, patients were randomized to receive either the calcium entry blocker nicardipine or placebo. All indicated concomitant medications except calcium entry blockers are permitted. Patients are being followed clinically for 24 months before undergoing a second coronary arteriogram. The effect of the treatments on a variety of clinical and angiographic parameters will be determined.

A controlled clinical trial to assess the effect of a calcium channel blocker on the progression of coronary atherosclerosis.

To determine whether calcium channel blockers influence the progression of coronary atherosclerosis, 383 patients age 65 years or less with 5-75% stenoses in at least four coronary artery segments were selected at random within 1 month of coronary arteriography to participate in double-blind therapy with a placebo or nicardipine 30 mg three times daily. Coronary events (5 deaths, 22 myocardial infarctions, and 28 unstable anginas) occurred in 28 of 192 nicardipine patients and 23 of 191 placebo patients (p = NS). At 24 months coronary arteriography was repeated in 335 patients. Progression, defined as a 10% or more worsening in diameter stenosis, measured quantitatively, was found in 147 of 1,153 lesions (12.7%) in 168 nicardipine patients and in 170 of 1,170 lesions (14.5%) in 167 placebo patients (p = NS). Ninety-two nicardipine patients (55%) and 95 placebo patients (57%) had progression at one or more sites (p = NS). Regression, that is, an improvement by 10% or more in diameter stenosis, was seen in 140 of 2,323 lesions (6.0%) overall, with no significant intergroup difference. Among the 217 patients with 411 stenoses of 20% or less in the first study, such minimal lesions progressed in only 15 of 99 nicardipine patients compared with 32 of 118 placebo patients (15% versus 27%, p = 0.046). In this subgroup, 16 of 178 minimal lesions in nicardipine patients and 38 of 233 minimal lesions in placebo patients progressed (p = 0.038). By stepwise logistic-regression analysis, baseline systolic blood pressure (p = 0.04) and the change in systolic blood pressure between baseline and 6 months (p = 0.002) correlated with progression of minimal lesions. This suggested blood pressure reduction may account for the beneficial action of nicardipine. These results suggested nicardipine has no effect on advanced coronary atherosclerosis but may retard the progression of minimal lesions.