Results From a Large,Multicenter, Retrospective Analysis On Radium223 Use in Metastatic Castration-resistant Prostate Cancer (mCRPC) in the Triveneto Italian Region

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.

Cavo-portal transposition in rat: a new simple model

Background  

Liver transplantation in presence of diffuse portal vein thrombosis is possible by using caval blood as portal inflow, through cavo-portal transposition. However, clinical results are heterogeneous and experimental studies are needed, but similar hemodynamic conditions are difficult to obtain, especially in small animals. Herein we describe a new simple model of cavo-portal transposition in rat.     

Preoperative Chemotherapy Alone and Combined with Preoperative Radiotherapy in Small-Size Breast Cancer

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.     

Gene probe for P0 messenger RNA used to index acrylamide toxic neuropathy in rats.

Cumulative exposure to the neurotoxicant acrylamide produces axonal damage in the distal ends of both central (CNS) and peripheral (PNS) nerve fibers and subsequent hind-limb paralysis. The messenger RNA which codes for the PNS myelin glycoprotein P0 (P0-mRNA) was used to monitor this toxic neuropathy in Sprague Dawley rats prior to, concurrent with, and subsequent to, ultrastructurally and immunocytochemically defined nerve damage. Rats were dosed every other day with acrylamide (50 mg/kg, IP) and sampled intermittently throughout a 4 week exposure period. Slot blot and Northern gel analyses of the proximal and distal sciatic nerve were used to determine a quantitated measure of P0-mRNA. Twenty-four hours after the first treatment, in the absence of ultrastructural damage, P0-mRNA increased 55% over control levels in the distal sciatic nerve. After 12 treatments, and concomitant with the appearance of spinal cord and PNS neuropathic damage and hindlimb dysfunction, P0-mRNA decreased 45% below control levels. Levels of P0-mRNA from rats exposed to 12 treatments of acrylamide but allowed to recover for 40 days, returned to 79% of control values to reflect the regeneration and remyelination occurring in the distal sciatic nerve. In spite of these fluctuations in levels of P0-mRNA, immunocytochemical staining of P0 protein in plastic sections of the distal sciatic nerve was present throughout all sample times. These results suggest that changes in neural specific mRNAs are sensitive to neurotoxic damage and can be used to monitor the pathogenesis of nerve degeneration.     

Release of newly synthesized h-dopamine in the striatum: An adaptation of the push-pull cannula method to awake restrained and anesthetized rats

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.     

Diagnosis and management of severe atherosclerosis of the ascending aorta and aortic arch during cardiac surgery: focus on aortic replacement

Objective: Severe atherosclerosis of the ascending aorta and arch frequently causes difficulties during heart operations, hindering surgical manoeuvres and potentially leading to systemic embolism. The aim of our study was to assess the safety and effectiveness of replacing the atherosclerotic ascending aorta in this setting. Methods: Aortic atherosclerosis was characterized by epiaortic ultrasonographic scanning in 90.1% of 1927 consecutive adult patients undergoing cardiac operations, and by computed tomographic chest scanning in selected cases. Thirty-six of the 152 patients requiring major derangements from our standard practice due to aortic atherosclerosis underwent replacement of the ascending aorta and constitute the study group. Replacement of the aorta was extended to the arch in 13 cases (36.1%). It was associated with single or multiple valve surgery in 34 patients (94.4%) and with coronary revascularization in 30 (83.3%). Two patients (5.6%) underwent coronary bypass grafting without valve surgery. A cryoablation procedure was associated in three patients with permanent atrial fibrillation. Deep hypothermic circulatory arrest was employed in 34 patients (94.4%), while proximal aortic disease allowed conventional distal crossclamping in 2 cases. The risk of operative mortality was estimated by the logistic EuroSCORE both with and withholding the variable ‘surgery of the thoracic aorta’. All survivors were followed-up for 1–41 months (16 ± 12). Results: Two patients died in the hospital (5.6%) and two during follow-up, for a cumulative survival of 91.3% and 85.6% at 1 and 3 years, respectively (hospital deaths included). The hospital death rate compared favourably with the expected estimates of 25.5% (p < 0.05) and 10.3% (p = 0.67) obtained by the EuroSCORE full model and without ‘aortic surgery’, respectively. In-hospital adverse neurologic events occurred in six patients (16.7%), including stroke in one patient (2.8%) and neurocognitive disturbances in five (13.9%), although they were all transient and cleared before discharge. Excess bleeding required re-exploration in four patients (11.1%), and one more patient underwent emergency grafting for acute postoperative coronary occlusion. Ten patients (38.5%) were intubated for longer than 24 h. Conclusion: Despite significant perioperative morbidity, replacement of the severely atherosclerotic aorta is worth consideration to avert expectedly higher death and stroke rates.     

Peritumoral lymphatic invasion in patients with node-negative mammary duct carcinoma.

Five hundred six consecutive cases of ductal infiltrating carcinoma of the breast (T1-T2,N0,M0) were evaluated to define the frequency of peritumoral lymphatic invasion (PLI) and verify its possible prognostic significance. Histologically, PLI was characterized by the presence of neoplastic emboli within vascular lumina lined by recognizable endothelial cells, adjacent to but outside the margins of the carcinoma. In routine histopathologic assessment the frequency of PLI was 68% whereas in a randomly selected group of 234 reviewed cases the frequency rose to 20%. Patients with routinely evaluated PLI had a worse prognosis than those without PLI with reference both to disease-free survival (P = 0.0001) and total survival rates (P = 0.0001). The difference for local recurrences was prognostically highly significant (P = 0.0001) and also significant for the development of metastases (P = 0.0576). In the reviewed material the difference in prognosis between PLI-positive and PLI-negative cases was not confirmed for total survival whereas the significance for the disease-free interval persisted. The assessment of PLI, carried out following strict histopathologic criteria, appears to select a group of node-negative breast cancer patients who have an increased risk of recurrences and might benefit from a treatment different from that reserved for node-negative and PLI-negative patients.     

Mondor's disease and breast cancer.

Mondor's disease or thrombophlebitis of the subcutaneous veins of the chest region is an uncommon condition and is rarely associated with breast cancer. From January 1980 to June 1990, 63 cases of Mondor's disease were diagnosed (57 women and 6 men). In 31 patients, no apparent cause was determined (primary disease), whereas in 32 cases, the disease was secondary because the etiopathogenesis could be discerned. The identified potential causes were three cases of myentasis (all in men), eight cases of accidental local trauma (seven in women), seven cases of iatrogenic origin (three surgical breast biopsies, one skin biopsy, one needle biopsy, one mastectomy, and one reconstruction operation), six cases of inflammatory process, and eight cases associated with breast cancer (all females). Three of the tumors were less than 1 cm in diameter. The authors performed conservative surgery in four patients and demolitive in the other four. In this series, the incidence of breast cancer in association with Mondor's disease was the highest yet reported (12.7%). It was concluded that Mondor's disease may at times be caused by breast carcinoma. This association is by no means exceptional and implies that mammography should always be performed for Mondor's disease, even when the results of a physical examination are negative.     

Transient hypoparathyroidism following thyroidectomy: a prospective study and multivariate analysis of 604 consecutive patients.

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.