Co-expression of cancer testis antigens and topoisomerase 2-alpha in triple negative breast carcinomas

Triple negative breast cancers (TNBC) are characterized by aggressive tumor biology, lack of targeted treatments and poor prognosis. Anthracyclins were shown to induce immunogenic death in target cells, potentially leading to “endogenous” vaccination. We comparatively assessed expression of cancer testis antigens (CTA) and topoisomerase 2-alpha (TOPO2A), a well defined molecular target of anthracyclins, in TNBC fully characterized for basal-like (BL) immunophenotype, BL morphology and conventional clinicopathological factors. The study included 83 patients undergoing surgery between January 2003 and December 2009. Tissue sections were stained with CK5/6, CK14, EGFR, Ki-67, TOPO2A, MAGE-A1, MAGE-A10, NY-ESO and multi-MAGE-A specific reagents. Of the 83 TNBC, >66.3% had BL immunophenotype and 48.2% had BL morphology. MAGE-A1 specific staining was most frequently detectable (69.2%), followed by multi-MAGE-A (58%), NY-ESO (27.1%) and MAGE-A10 (16%) specific staining. MAGE-A10 expression significantly correlated with tumor size (p = 0.026). Furthermore, MAGE-A1, MAGE-A10 and multi-MAGE-A specific stainings significantly correlated with advanced clinical stage (p = 0.024, p = 0.041, p = 0.031, respectively). We found no significant association between CTA expression and disease free (DFS) or overall survival (OS). Most interestingly, a significant correlation was observed between expression of MAGE-A10 and NY-ESO and expression of TOPO2A (p = 0.005, p = 0.013). Expression of defined CTA and TOPO2A are significantly correlated in TNBC. Considering the limited therapeutic options for TNBC, these findings might suggest novel forms of combination therapies that should be further explored.     

Twenty-five-gauge vitrectomy versus 23-gauge vitrectomy in the management of macular diseases: a comparative analysis through a Health Technology Assessment model

Small-gauge vitreoretinal techniques have been shown to be safe and effective in the management of a wide spectrum of vitreoretinal diseases. However, the costs of the new technologies may represent a critical issue for national health systems. The aim of the study is to plan a Health Technology Assessment (HTA) by performing a comparative analysis between the 23- and 25-gauge techniques in the management of macular diseases (epiretinal membranes, macular holes, vitreo-macular traction syndrome). In this prospective study, 45–80-year-old patients undergoing vitrectomy surgery for macular disease were enrolled at the Torino Eye Hospital. In the HTA model we assessed the safety, clinical effectiveness, and cost and financial evaluation of 23-gauge compared with 25-gauge vitrectomies. Fifty patients entered the study; 14 patients underwent 23-gauge vitrectomy and 36 underwent 25-gauge vitrectomy. There was no statistically significant difference in post-operative visual acuity at 1 year between the two groups. No cases of retinal detachment or endophtalmitis were registered at 1-year follow-up. The 23-gauge technique was slightly more expensive than the 25-gauge: the total surgical costs were EUR1217.70 versus EUR1164.84 (p = 0.351). We provide a financial comparison between new vitreoretinal procedures recently introduced in the market and reimbursed by the Italian National Health System and we also stimulate a critical debate about the expensive technocratic model of medicine.     

Atrial flutter termination by overdrive transesophageal pacing and the facilitating effect of oral propafenone

Transesophageal overdrive atrial pacing is effective and safe for atrial flutter termination. The influence of antiarrhythmic drug therapy on this procedure is controversial. In this study, we investigated whether oral propafenone may facilitate this procedure. Thirty patients with type I atrial flutter were randomized into 2 groups in which transesophageal pacing was attempted: group A, without treatment; and group B, after oral administration of propafenone 600 mg. Transesophageal pacing was effective in interrupting atrial flutter in 53% of patients (8 of 15) in group A and in 87% of patients (13 of 15) in group B. A significant lengthening of the flutter cycle was observed with respect to the baseline in patients given propafenone (261 ± 23 vs 217 ± 25, p < 0.01). Sinus rhythm resumed at a shorter paced cycle in group A patients (166 ± 13 vs 187 ± 14 ms, p < 0.01). The transesophageal threshold for stable atrial capture was significantly lower in group A (20.5 ± 0.2 vs 23.3 ± 1.2, p < 0.01). In no patient was the threshold for atrial capture higher than the pain threshold. We did not observe abrupt enhancement of atrioventricular conduction. We conclude that propafenone is effective and safe when used with transesophageal pacing in the termination of atrial flutter. The slowing effect of the drug on intraatrial conduction and the possible stabilizing effect on the reentry circuit appear to be outweighed by the positive effect of propafenone on the excitable gap of the circuit, facilitating its capture and accounting for the beneficial effect of the drug on arrhythmia termination.