Is subareolar intraoperative biopsy still necessary to predict nipple involvement?

OBJECTIVE: To predict the occult tumor involvement of nipple-areola complex (NAC) using preoperative MR imaging and to investigate whether the intraoperative histopathological examination of the subareolar tissue is still necessary. PATIENTS AND METHODS: Out of 712 patients submitted to nipple-sparing mastectomy (NSM) between 2014 and 2019, we selected 188 patients who underwent preoperative breast MRI. Breast MRI and intraoperative histopathological examination of the subareolar tissue were performed to predict NAC involvement at permanent pathology. All parameters were correlated with final pathological NAC assessment by univariate and multivariate analysis. RESULTS: Forty-three patients (22.9%) had tumor involvement of the NAC. At univariate analysis, non-mass enhancement type (p = 0.009), multifocality/multicentricity (p = 0.002), median tumor size (p < 0.001), median tumor-NAC distance measured by MRI (p < 0.001), tumor-NAC distance ≤ 10 mm (p < 0.001) and tumor-NAC distance ≤ 20 mm (p < 0.001), and lymphovascular invasion (p = 0.001) were significantly correlated with NAC involvement. At multivariate analysis, only tumor-NAC distance ≤ 10 mm retained statistical significance. The sensitivity and specificity of MRI tumor-NAC distance ≤ 10 mm were 79.1% and 97.2% and those of intraoperative pathologic assessment were 74,4% and 100%, respectively. CONCLUSIONS: Tumor-NAC distance is the only reliable MRI characteristic that can predict NAC involvement in breast cancer patients. Although several cut-offs showed promising performances, intraoperative pathologic assessment is still mandatory.

Prognostic value of ventricular arrhythmias and heart rate variability in patients with unstable angina.

OBJECTIVES: To assess the prognostic value of ventricular arrhythmias (VA) and heart rate variability (HRV) in patients with unstable angina. DESIGN: Multicentre prospective study. SETTING: 17 cardiological centres in Italy. PATIENTS: 543 consecutive patients with unstable angina and preserved left ventricular function (ejection fraction >or=40%) enrolled in the SPAI (Stratificazione Prognostica dell'Angina Instabile) study. METHODS: Patients underwent 24 h ECG Holter monitoring within 24 h of hospital admission. Tested variables were frequent ventricular extrasystoles (>or=10/h), complex (that is, frequent or repetitive) VA, and bottom quartile values of time-domain and frequency-domain HRV variables. Primary end points were in-hospital and six-month total and cardiac deaths. RESULTS: Eight patients died in hospital (1.5%) and 32 (5.9%, 29 cardiac) during follow up. Both complex VA and frequent extrasystoles were strongly predictive of death in hospital and at follow up, even after adjustment for clinical (age, sex, cardiac risk factors and history of myocardial infarction) and laboratory (troponin I, C reactive protein and transient myocardial ischaemia on Holter monitoring) variables. At univariate analysis bottom quartile values of three HRV variables (standard deviation of RR intervals index, low-frequency amplitude and low to high frequency ratio) were associated with in-hospital death, and bottom quartile values of most HRV variables predicted six-month fatal events. At multivariate Cox survival analysis reduced low-frequency amplitude was consistently found to be independently associated with fatal end points. CONCLUSION: In patients with unstable angina with preserved myocardial function, both VA and HRV are independent predictors of in-hospital and medium-term mortality, suggesting that these factors should be taken into account in the risk stratification of these patients.

Nitrate tolerance in patients with effort angina.

BACKGROUND: In some patients with chronic stable angina the beneficial effects of nitrates may result not only from a reduction in venous return, but also from their action on coronary circulation. In these patients, rate-pressure product at ischemia (RPPI) increases to > 2500 bpm x mmHg after sublingual nitrates (SLN). The relative susceptibility of the venous system and the coronary circulation to the development of nitrate tolerance and the effects of two different drug schedules on the development of tolerance were investigated in patients with these characteristics. METHODS: Five patients were treated with isosorbide-5-mononitrate (IS5MN) 20 bid (8.00 am and 3.00 pm) for 1 week (Group 1) and 5 patients with IS5MN 40 bid (8.00 am and 8.00 pm) for 1 week (Group 2). Tolerance was identified as the decreased effect of SLN; the effects of nitrates were evaluated in relation to: reduction in left ventricle area (delta LVA), which had been measured using equilibrium radionuclide ventriculograms in LAO 45 degrees; this area was considered as an index of the venous return effects; increase in RPPI (delta RPPI), which had been assessed by ergometric test; RPPI was considered an index of coronary flow reserve. Measurements of LVA and RPPI were made in wash-out at the start of the study (delta LVA 1 and delta RPPI 1) and after 1 week of treatment (delta LVA 2 and delta RPPI 2). The mean values of the differences were then evaluated and compared using Student's "t" test. RESULTS AND CONCLUSIONS: In Group 1 patients delta LVA 2 and delta RPPI 2 showed values which were similar to delta LVA 1 and delta RPPI 1 (mean value delta LVA 2 47 vs mean delta LVA 1 48.2 pixels, p = ns; mean value delta RPPI 2 5264 vs mean delta RPPI 1 5536 bpm x mmHg, p = ns). These results suggest that Group 1 patients did not develop tolerance either at the coronary or at the venous level. In Group 2 patients, delta LVA 2 was significantly lower than delta LVA 1 (mean delta LVA 2 18.4 vs mean delta LVA 1 54 pixels, p < 0.01). This finding indicated tolerance to nitrates at the venous level. On the other hand, in all Group 2 patients, values of delta RPPI 2, though lower than delta RPPI 1 (mean delta RPPI 2 3095 vs mean delta RPPI 1 6083 bpm x mmHg, p < 0.01) were still higher than 2500 bpm x mmHg, indicating that the effect of nitrates at the coronary level was preserved. These data suggest that in patients treated with high doses of nitrates, the effect of these drugs at the coronary level is still present when tolerance has already developed at the venous level.

Efficacy of carvedilol in mild to moderate essential hypertension and effects on microalbuminuria: a multicenter, randomized, open-label, controlled study versus atenolol.

In this randomized, open-label, multicenter comparison, 140 adults with mild to moderate essential hypertension were treated with the nonselective beta blocker carvedilol (25 mg once daily) or the selective beta 1 blocker atenolol (100 mg once daily) orally for 2 months. Systolic and diastolic blood pressure and heart rate were measured monthly in the supine and standing positions. Urinary albumin levels and blood lipid profile were determined at baseline and at study end. The occurrence of cold extremities was monitored throughout the study. Both treatments significantly decreased systolic and diastolic blood pressure at a comparable level. At the final assessment, 88% of the carvedilol group achieved a supine diastolic blood pressure of 90 mm Hg or lower, compared with 82% of the atenolol group. Atenolol produced the greater decrease in heart rate, but between-group differences were significant only for standing measurements. With carvedilol, urinary albumin decreased in 25% of patients and increased in 2%; corresponding figures with atenolol were 13% and 12%. At study end, 10% of the carvedilol group and 37% of the atenolol group complained of cold extremities. No major between-group differences were observed in the percentage of patients with an increase in high-density lipoprotein or a decrease in low-density lipoprotein cholesterol. Triglycerides and total cholesterol tended to decrease in a greater percentage of patients taking carvedilol than atenolol.

[Adaptation to effort myocardial ischemia]. / Adattamento all'ischemia miocardica da sforzo.

BACKGROUND: During PTCA it has been observed that in two sequential coronary occlusions, the second is characterized by less subjective anginal discomfort, less ST segment depression, less myocardial lactate production and lower mean pulmonary pressure than that recorded during the first inflation. The phenomenon is known as "cardiac adaptation to ischemia". PTCA, as a model for controlled, reversible myocardial ischemia must be viewed in a substantially different context from other models concerning different types of ischemia. The purpose of our investigation was to examine the hypothesis that phenomena similar to those observed during PTCA can occur during effort ischemia. METHODS: Six patients with stable effort ischemia, fixed ischemic threshold (bpm x mmHg variability less than 3200) and fixed recovery period (variability of time at ST on isoelectric line less than 1 min and variability of rate-pressure product at ST on isoelectric line less than 2000 bpm x mmHg) were studied. Our aim was to study the ischemic threshold (IT) and the recovery period in an exercise test performed a short time after an initial one. The programme consisted of: 1) exercise test at a fixed load (the load was predetermined by the level of ischemia reached in a previous multistage exercise test); 2) exercise test ending at ST decreases 1 mm; 3) recovery period; 4) 2nd exercise test similar to the first one and ending at ST decreases 1 mm, to be performed 3 minutes after the end of recovery period (that is, 3 minutes after ST on isoelectric line). In both exercise tests we registered rate-pressure product at ischemia (RPPI), time to ischemia (TI), rate-pressure product at ST on isoelectric line (rate-pressure product at normalization: RPPN) and time at ST on isoelectric line (time of normalization: TN). RESULTS: [table: see text] In all pts RPPI in the second exercise test was similar to RPPI registered in the first one, while RPPN in the second exercise test was higher than in the first. In the second exercise test, time to ST on isoelectric line was also shorter. CONCLUSIONS: We think that the shorter recovery period from myocardial ischemia in the second exercise test may be an expression of a "cardiac adaptation to ischemia", a phenomenon which has been previously observed during PTCA.