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1.

Background

Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting.

Patients and Methods

We conducted a multicenter retrospective analysis in the Triveneto region of Italy.

Results

One hundred fifty-eight patients received radium 223 in our region. After a median follow-up of 9.5 months, 75 patients died. The median overall survival (OS) was 14.2 months, and the median progression-free survival (PFS) was 6.2 months. Seventy-one (45%) patients achieved progression as best response. Thirty-seven (23%) patients stopped the treatment early because of progression. Eastern Cooperative Oncology Group performance status was prognostic for OS (18.4 vs. 12.3 vs. 7.5 months; 0 vs. 1, P = .0062; 0 vs. 2, P = .0002), whereas previous prostatectomy or docetaxel exposure were not. A neutrophil to lymphocytes ratio ≥ 3 significantly impacted OS (18.1 vs. 9.7 months; P < .001) and slightly impacted PFS (6.6 vs. 5.6 months; P = .05). Patients with a baseline alkaline phosphatase (ALP) value ≥ 220 U/L had worse OS and PFS (24.1 vs. 10.5 months; 7.2 vs. 5.5 months; P < .001). Patients with changes in ALP value achieved better OS (P = .029) and PFS (P = .002). There was no difference according to the line of therapy (0 vs. ≥ 1; P = .490). The main grade 3/4 toxicities were anemia, asthenia, and thrombocytopenia.

Conclusion

This large real-world report confirms comparable OS and PFS data when compared with the pivotal study, as well as the predictive role of ALP and neutrophil to lymphocytes ratio. The definition of the optimal position of radium 223 in the treatment of metastatic castration-resistant prostate cancer has still to be defined.  相似文献   
2.
Abstract: Breast conservation surgery is an effective and safe treatment for many breast carcinomas. It may be possible to further limit the extent of resection (or expand the indication for breast conservation) by the application of preoperative chemotherapy and radiotherapy. We explored the feasibility of this in a pilot study.
Seventy-three patients (mean age 48, 63% premenopausal) with confirmed breast cancer, less than 2.5 cm, received chemotherapy (Group A) or chemotherapy plus radiotherapy (Group B) prior to limited resection (tumorectomy). Axillary dissection was always performed. Results: In 6/31 (19%) Group A and 17/42 (40%) Group B patients the tumor was not palpable after preoperative treatment, with complete pathological remission in 1 and 3 cases respectively. Histologic grading, mitosis, cellular alteration, and cellularity evaluations indicated a consistently greater therapeutic effect with chemoradiotherapy than with chemotherapy alone.
In conclusion, radiotherapy appears useful in the preoperative treatment of breast cancer and its use in association with various drug combinations should be further explored.  相似文献   
3.
The release of newly synthesized 3H-dopamine (3H-DA) was measured in the rat striatum superfused, through a push-pull cannula, with a physiological medium enriched in 3H-tyrosine. The level of spontaneous 3H-DA release was dependent on the topographical localisation of the cannula in the striatum (anterior parts displayed higher levels than posterior ones) and on the anesthetic state (halothane anesthetized rats demonstrated higher levels than awake ones). Inhibition of DA inactivation processes by local application of benztropine (a DA reuptake inhibitor, 10−6 M) or by IV administration of pargyline (a MAO inhibitor, 100 mg/kg) enhanced the detectable outflow of 3H-DA from the striatum in both halothane anesthetized and awake rats. Local application of D-amphetamine (10−5 M) or acetylcholine (5 × 10−5 M) in the presence of eserine (5 × 10−5 M) evoked respectively a fivefold and a 30% increase in spontaneous 3H-DA release in halothane anesthetized rats. Inhibition of the firing of dopaminergic neurons by IV injection of gamma-hydroxybutyrate (400 mg/kg) produced a 30% decrease in striatal 3H-DA release. The present results demonstrate that the push-pull cannula method is suitable for the study of DA release in both the anesthetized and the awake rat.  相似文献   
4.
OBJECTIVE: The purpose of this study was to identify the risk factors for postoperative transient hypoparathyroidism in a group of patients undergoing thyroid surgery. STUDY DESIGN: A prospective study was conducted on 604 patients undergoing thyroid surgery. SUBJECTS AND METHODS: Gender, final diagnosis, extent of resection, biology of pathology, intrathoracic involvement, surgery for recurrent multinodular goiter, and presence and number of parathyroid glands in a surgical specimen were analyzed as risk factors for postoperative transient hypoparathyroidism. The chi-square test and a logistic regression analysis were applied. RESULTS: On logistic regression analysis, only the extent of surgery constituted an independent variable for transient hypoparathyroidism (P = 0.001). CONCLUSION: The extent of surgery to central and/or lateral neck lymph nodes is responsible for a high rate of transient hypoparathyroidism owing to a high probability of unplanned parathyroidectomy or parathyroid gland devascularization.  相似文献   
5.
As a part of our interest in the performance of [Ti2(OC2H5)8Cl]2Mg2(μ-Cl)2 as Ziegler-Natta catalyst, the polymerization of styrene with a toluene solution of this compound and methyl-aluminoxane as cocatalyst was performed. It was found that the present catalytic system promotes the syndiospecific polymerization of styrene with high stereoregularity and the results were compared with those obtained with MgCl2-supported or unsupported Ti(OC2H5)4 catalysts. Determination of the titanium oxidation states and electron spin resonance (ESR) measurements both in the absence and in the presence of styrene were carried out for all the catalytic systems aimed at shedding some light on the nature of the active species.  相似文献   
6.
A reduction in muscle mass, with consequent decrease in strength and resistance, is commonly observed with advancing age. In this study we measured markers of oxidative damage to DNA, lipids and proteins, some antioxidant enzyme activities as well Ca2+ transport in sarcoplasmic reticulum membranes in muscle biopsies from vastus lateralis of young and elderly healthy subjects of both sexes in order to evaluate the presence of age- and sex- related differences. We found a significant increase in oxidation of DNA and lipids in the elderly group, more evident in males, and a reduction in catalase and glutathione transferase activities. The experiments on Ca2+ transport showed an abnormal functional response of aged muscle after exposure to caffeine, which increases the opening of Ca2+ channels, as well a reduced activity of the Ca2+ pump in elderly males. From these results we conclude that oxidative stress play an important role in muscle aging and that oxidative damage is much more evident in elderly males, suggesting a gender difference maybe related to hormonal factors.This revised version was published online in September 2005 with corrections to the Cover Date.  相似文献   
7.
8.
Liver transplantation (LT) for colorectal liver metastasis (CRLM) may provide excellent survival rates in patients with unresectable disease. High tumor load is a risk factor for recurrence and low overall survival (OS) after liver resection (LR). We tested the hypothesis that LT could offer better survival than LR in patients with high tumor load. LR performed at Padua University Hospital for CRLM was compared with LT for unresectable CRLM performed both at Oslo and Padua. High tumor load was defined as tumor burden score (TBS) ≥ 9, and inclusion criteria were as in the SECA-I transplant study. 184 patients were eligible: 128 LRs and 56 LTs. 5-year OS after LR and LT was 40.5% and 54.7% (= 0.102). In the high TBS cohort, 5-year OS after LR and LT was 22.7% and 52.2% (P = 0.055). In patients with Oslo score ≤ 2 and TBS ≥ 9 (13 LR; 24 LT) the 5-year OS after LR and LT was 14.6% and 69.1% (P = 0.002). The corresponding disease-free survival (DFS) was 0% and 22.9% (P = 0.005). Selected CRLM patients with low Oslo score and high TBS could benefit from LT with survival outcomes that are far better than what is achieved by LR.  相似文献   
9.
The possible involvement of nitric oxide in the prevention by morphine of apomorphine- and oxytocin-induced penile erection and yawning was investigated by measuring the concentration of NO2- and NO3- in the dialysate obtained with a vertical microdialysis probe implanted in the paraventricular nucleus of the hypothalamus of male rats. Either apomorphine (80 μg/kgs.c.) or oxytocin (30 ng i.c.v.) increased significantly basal NO2- and NO3- concentration in the paraventricular dialysate, penile erection and yawning. Morphine (1, 5 and 10mg/kg i.p.) prevented dose-dependently either apomorphine or oxytocin responses when given 15min before apomorphine or oxytocin. Prevention by morphine of apomorphine and oxytocin responses was abolished by naloxone (3mg/kg i.p.) given 15min before morphine. Morphine prevented apomorphine and oxytocin responses also when given in the lateral ventricles or directly in the paraventricular nucleus. In contrast, the selective agonist of the kappa opioid receptor subtype U-69,593 was found to be ineffective. The present results confirm previous findings showing that morphine acts through μ receptors in the paraventricular nucleus to prevent apomorphine and oxytocin-induced penile erection and yawning and suggest that this morphine effect is mediated by a decreased activity of nitric oxide in the paraventricular nucleus of the hypothalamus. Received: 30 September 1996 / Accepted: 24 January 1997  相似文献   
10.
The locomotor activity of C57B1/6J and DBA/2J mice was studied, under the influences of heroin, amphetamine, strychnine, or ethanol, and of combinations of the opiate with each one of the other drugs. Heroin treatment was followed by the typical running fit in the C57 mice, while the DBA strain was unaffected. Amphetamine enhanced the activity in the C57 strain only. The combination of heroin with amphetamine or ethanol increased the locomotor activity only in the DBA strain, while heroin + strychnine exerted a clear stimulating effect on the activity of the C57 mice. The strychnine + heroin mixture was more toxic than heroin alone when the lethal doses (LD50) were determined in the 2 strains.  相似文献   
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