Renato Costa

Effects of amlodipine on renal haemodynamics in mild to moderate hypertensive patients

SummaryIn this study the efficacy and safety of short-term amlodipine administration on renal haemodynamics were evaluated in mild to moderate hypertensive subjects. Our final goal was to evaluate whether the reduced blood pressure induced by treatment was associated with maintenance of renal function.After a run-in period with placebo, 30 hypertensive patients without cardiac or renal diseases were randomly allocated to a double-blind 4 weeks controlled study with amlodipine 10 mg once a day (15 patients) or placebo (15 patients).Renal haemodynamic measurements included effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) by radionuclide study using 131I-hippuran and 99mTc, with methods described by Schlegel and Gates, respectively. In addition, effective renal blood flow [ERBF=ERPF/(1-Ht)], filtration fraction (FF=GFR/ERPF) ERPF) and renal vascular resistance (RVR=MBP×80/ERBF) were calculated. Plasma renin activity (PRA), serum aldosterone (ALD) and urinary excretion of sodium (NaU) were evaluated.At the end of amlodipine administration a significant decrease (P<0.001) in SBP, DBP and MBP from baseline values was observed. A significant decrease (P<0.01) in RVR and significant increases (P<0.05) in ERPF, ERBF and in NaU were also found, without relevant changes in GFR, FF, PRA and ALD.No significant variation in clinical and renal measurements was observed in the placebo group.No relevant side effects were observed in either group. In conclusion, amlodipine was effective in lowering blood pressure in mild to moderate hypertension and exerted favourable effects on renal haemodynamics and function.

Lymphoscintigraphy with peritumoral injection versus lymphoscintigraphy with subdermal periareolar injection of technetium-labeled human albumin to identify sentinel lymph nodes in breast cancer patients

Background Preoperative lymphoscintigraphy is without doubt a valid method for the detection of the sentinel lymph node (SLN). There has been considerable debate regarding the optimal site for the introduction of the tracer; various sites include peritumoral (PT), periareolar (PA), subdermal, and intradermal injection. Purpose To evaluate retrospectively the lymphoscintigraphic identification rate of peritumoral (PT) injection versus subdermal periareolar (PA) injection in the detection of SLNs in breast cancer. Material and Methods Between October 2002 and December 2011, a cohort of 906 consecutive patients with biopsy proven breast cancer underwent 914 SLN biopsy procedures. A total of 339 procedures (Group A) were performed using a PT deep injection of radiotracer while 575 procedures (Group B) adopted a subdermal PA injection of radiotracer towards the upper outer quadrant, regardless of the site of the carcinoma. All the patients underwent synchronous excision of the breast cancer and SLN biopsy. Results SLNs were identified in the lymphoscintigram in 308/339 cases (90.85%) of Group A (PT injection) and in 537/575 cases (93.39%) of Group B (PA injection). Furthermore, in 2/339 patients (0.58%) of Group A, internal mammary lymph nodes were found at lymphoscintigraphy, whereas no internal mammary sentinel nodes were found in the Group B patients. The intraoperative identification rate of axillary SLNs was 99.41% (337 of 339) in the Group A patients and 99.65% (573 of 575) in the Group B patients. There was no significant difference in the two groups between the incidence of the number of SLNs detected and the incidence of identification of positive SLNs. Conclusion PT versus PA injection of radiotracer showed comparable success rates for axillary SLN identification, and can be considered a rapid and reliable method.

Effect of Long-Term Losartan Administration on Renal Haemodynamics and Function in Hypertensive Patients

In this study the efficacy and safety of long-term losartan administration on renal haemodynamics were evaluated in mild to moderate hypertension. After a run-in period with placebo, 18 hypertensives without renal or cardiovascular disease were allocated to losartan (50 mg/die for one year) treatment. Renal haemodynamic measurements included renal plasma flow (ERPF) and glomerular filtration rate (GFR) by standardized radioisotope study. Effective renal blood flow (ERBF), filtration fraction (FF), and renal vascular resistance (RVR) were also calculated. Blood pressure was evaluated monthly, whereas renal haemodynamics and function were detected at baseline and after 6 and 12 months of losartan administration. Losartan induced a significant (p < 0.001) decrease in SBP, DBP, and MBP versus baseline values both at 6 months and at 12 months. In addition a significant decrease in RVR (p < 0.001) and in FF (p < 0.05) was also seen. In addition RVR values at 1 year of treatment were higher than their values at 6 months, but this difference was not significant. Our data indicated that long-term control in blood pressure induced by losartan administration was associated with a maintained renal function after 6 months of treatment, but these favourable effects were attenuated after 1 year of treatment.

Two-dimensional echocardiographic evaluation of left ventricular ejection fraction by the ellipsoid single-plane algorithm: a reliable method for assessing low or very low ejection fraction values?

The reliability of two-dimensional (2D) echocardiographic estimation of left ventricular ejection fraction (EF) is commonly recognized, but no satisfactory data are available about the accuracy of low or very low EF values determined by 2D echocardiography (ECHO-EF). The purpose of our study was to assess the reliability of low ECHO-EF values obtained using a simple time-economical algorithm such as the ellipsoid single-plane area-length method. Radionuclide angiography (RAD-EF) was taken as the standard of comparison. We studied 59 consecutive patients (31 women and 28 men) referred to our echocardiographic laboratory. Both 2D echocardiography and radionuclide angiography were blindly performed within 48 h of one another. EF was calculated by the two methods and then compared. Data were globally analyzed. Furthermore, data were divided and analyzed according to the ECHO-EF cut-off point of 50%. An ECHO-EF value of 50% was chosen to conventionally distinguish between low ECHO-EF values and normal-high ones. Data were plotted, and the line of equality and the regression lines were drawn. Regression line slopes, correlation coefficients, means and standard deviations were calculated. The agreement was analyzed by calculating the mean difference (RAD-EF-ECHO-EF) and the standard deviation of the differences. ECHO-EF was linearly related to RAD-EF even when data were split. In particular, as regards ECHO-EF < or = 50%, the regression line practically overlapped the line of equality, and the two methods showed both a strong correlation and a good degree of agreement.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the Upper Limb Lymphatic System: A Prospective Lymphoscintigraphic Study in Melanoma Patients and Healthy Controls.

Background: Current research on the upper limb lymphatic system mainly studies breast cancer patients with unilateral lymphedema. Without preoperative lymphoscintigraphy, the contralateral limb is used as a control, assuming that it is functionally intact. Few lymphoscintigraphic studies investigate patients before any axillary surgery. The purpose of this study was to evaluate, through lymphoscintigraphy, the preoperative condition of the upper limb lymphatic system in melanoma patients and healthy controls. Methods: Two groups were studied: the study group (16 patients with trunk/upper limb melanoma candidates for axillary sentinel lymph node biopsy) and the control group (10 healthy volunteers). All subjects underwent upper limb lymphoscintigraphy. Lymphoscintigraphic images were classified into three patterns based on the tracer appearance time in the axillary nodes. Type I, 20 minutes; type II, 60 minutes; and type III, 120 minutes. Statistical analysis was used to assess the relationship between lymphoscintigraphic patterns and clinical variables and to compare patterns of distribution. Results: Lymphoscintigraphic patterns were asymmetric in 37.5 percent (study group) and 50 percent (control group). Type III was the most common pattern. There was no significant association between lymphoscintigraphic patterns and considered clinical variables. There was no significant difference in the lymphoscintigraphic pattern distribution of the two groups (p = 0.870). Conclusion: The authors’ findings show wide differences and an often “slow” tracer appearance time in patients with intact lymphatic system, questioning the use of contralateral limb as control and transportation time greater than 30 minutes as criteria for identification of lymphatic alterations. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.

Effects of cilazapril on renal haemodynamics and function in hypertensive patients: a randomised controlled study versus hydrochlorothiazide

In this study the efficacy and safety of short-term cilazapril administration on renal haemodynamics were evaluated in mild to moderate hypertensive subjects. Our final goal was to evaluate whether the reduction in blood pressure achieved by treatment was associated with maintained renal function. After a run-in period with placebo, 40 hypertensive subjects without renal or cardiac diseases were randomly allocated to a double-blind 4 week controlled trial with cilazapril 5 mg once a day (20 patients) or hydrochlorothiazide 25 mg once a day (20 patients). Renal haemodynamics measurements included effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) by radionuclide study using 131I-hippuran and 99mTc, according to the methods described by Schlegel and Gates, respectively. Effective renal blood flow [ERBF = ERPF/(1-Ht)], filtration fraction (FF = GFR/ERPF) and renal vascular resistance (RVR = MBP x 80/ERBF) were calculated. At the end of cilazapril and hydrochlorothiazide administration significant decreases (p < 0.001) in SBP, DBP and MBP vs baseline values were observed. In the cilazapril group a significant decrease (p < 0.001) in RVR and FF and a significant increase (p < 0.001) in ERPF and ERBF were also found. In the hydrochlorothiazide group a significant decrease (p < 0.001) in RVR was found. No important side effects were observed with either treatment. In conclusion our data indicate that both cilazapril and hydrochlorothiazide reduced blood pressure equally well but only cilazapril improved renal blood flow and reduced filtration fraction.

Botulinum toxin in preparation of oral cavity for microsurgical reconstruction

Conclusions. Infiltration of botulinum toxin in the major salivary glands allows a temporary reduction of salivation that begins 8 days afterwards and returns to normal within 2 months. The inhibition of salivary secretion, carried out before the oral cavity reconstructive surgery, could allow a reduction of the incidence of oro-cutaneous fistulas and local complications. Objectives. Saliva stagnation is a risk factor for patients who have to undergo reconstructive microsurgery of the oral cavity, because of fistula formation and local complications in the oral cavity. The authors suggest infiltration of botulinum toxin in the major salivary glands to reduce salivation temporarily during the healing stage. Patients and methods. During the preoperative stage, 20 patients with oral cavity carcinoma who were candidates for microsurgical reconstruction underwent sialoscintigraphy and a quantitative measurement of the salivary secretion. Injection of botulinum toxin was carried out in the salivary glands 4 days before surgery. The saliva quantitative measurement was repeated 3 and 8 days after infiltration, sialoscintigraphy after 15 days. Results. In all cases, the saliva quantitative measurement revealed a reduction of 50% and 70% of the salivary secretion after 72 h and 8 days, respectively. A lower rate of local complications was observed.

Ra223 in bone metastases with osteolytic activity

Radium 223 dichloride (Ra223) is the only targeted alpha therapy able to extend survival in patients with bone metastases from prostate cancer. Mechanism of action and data currently available focused mainly on osteoblastic metastases from prostate cancer. In our institution, a patient with breast cancer affected by osteolytic metastases was treated with off-label use of Ra223. The evaluation of the deposit areas of Ra223 showed a perfect overlap with the regions of osteolysis previously detected by scintigraphy, indicating a possible therapeutic effect. This case report is the first document attesting Ra223 deposit in osteolytic metastases opening new opportunity of therapeutic development for this radiopharmaceutical.

Hematologic toxicity of radium-223 in elderly patients with metastatic Castration Resistant Prostate Cancer: a real-life experience

Background Treatment with radium-223 has been shown to increase survival and to delay skeletal events related to bone metastases of patients with metastatic Castration Resistant Prostate Cancer (mCRPC). This treatment has also proved to be well tolerated, and hematological toxicity, in particular anemia, represents the most represented adverse event. Materials and methods We evaluated the hematologic toxicity of Ra-223 treatment in a real-life experience of 38 patients from two Italian cancer centers, with bone metastases from mCRPC. The main endpoint of the study was the evaluation of the efficacy and tolerability of treatment with radium-223, with greater reference to hematological toxicity (especially anemia) as the cause of interruption of treatment, specifically in the elderly patient. Results From August 2016 to October 2017, a total of 38 consecutive nonselected patients, 20 of them aged >75 years, with mCRPC symptomatic bone metastases, were enrolled for radium-223 at standard doses. Hematologic adverse events were recorded more frequently (72.4% with AE), and 36.8% had anemia. The most frequent cause of treatment discontinuation due to AEs was anemia [8/10 patients (80%)], followed by thrombocytopenia (2 patients) and neutropenia (1 patient). Hematologic AEs were more represented in elderly patients with greater disease burden and previously treated with docetaxel. Conclusions Anemia is the most represented AE related to radium-223 treatment in elderly patients with greater disease burden and previously treated with docetaxel, besides representing the main reason for interruption of treatment. Correct patient selection, appropriate timing, and adequate supportive care are elements that could facilitate successful treatment with radium-223, preventing premature interruption of the same. The results of this experience support the opportunity to propose treatment with radium-223 mostly in patients in the earliest stages.

The Clinical Efficacy of Radium-223 for Bone Metastasis in Patients with Castration-Resistant Prostate Cancer: An Italian Clinical Experience

Background/Aim: Prostate cancer frequently causes bone metastases and skeletal events that impair quality of life (QoL) and survival. The alpha emitter radium-223 is a new drug that improves treatment in men with castration-resistant prostate cancer (CRPC) and bone metastases. Our aim was to evaluate the effectiveness of radium-223. Subjects and Methods: In this retrospective study we enrolled 48 subjects. Pain reduction, alkaline phosphatase (ALP), time to first symptomatic skeletal event, and QoL were the variables we evaluated. Results: Radium-223 was well tolerated, with a manageable toxicity profile and a modest objective response rate. A considerable difference in serum ALP levels before and after treatment was observed, with a significant correlation between pain relief and QoL, which showed a value of R2 to 0.44 with a slope of 1.50 (p = 0.0021). Conclusions: Radium-223 showed a clinical benefit, with a reduction in pain symptoms in 58% of patients. Radium-223 was shown to be an effective and well-tolerated therapeutic option in patients with metastatic CRPC progressing after docetaxel plus prednisone treatment.