Long-term outcome of neoadjuvant systemic therapy for locally advanced breast cancer in routine clinical practice

Purpose

The aim of this study is to evaluate the long-term outcome of patients with locally advanced breast cancer treated with neoadjuvant systemic chemotherapy (NST) in routine clinical practice.

Methods

Four hundred and nine patients were identified between January 1999 and December 2011. All patients received NST followed by surgery, adjuvant treatments and radiotherapy, as appropriate.

Results

At Kaplan–Meier analysis, patients with surgical stage III disease were more likely to develop distant metastasis and die from breast cancer (p < 0.001). Luminal A and luminal B/HER2-negative patients had better prognosis; moreover, patients with hormone receptor (HR)-positive tumors had a significantly longer DRFS (p < 0.0049) and OS (p < 0.0001) compared with patients with HR-negative tumors as well as patients who underwent breast-conserving surgery (DRFS and OS: p < 0.001). In multivariate analysis, HR negativity (p < 0.001 for both DRFS and OS), mastectomy (DRFS: p = 0.009; OS: p = 0.05) and stage III disease (DRFS: p < 0.001; OS: p = 0.003) were associated with shorter DRFS and OS.

Conclusions

HR negativity, mastectomy and pathological stage III disease are the variables independently associated with a worse outcome in our cohort of patients. These data are of high interest since they derive from a very heterogeneous group of patients, treated with different neoadjuvant/adjuvant regimens outside of clinical trials and with a long follow-up period.     

The role of transcranial Doppler in carotid artery surgery.

In order to evaluate the usefulness of transcranial Doppler (TCD) in carotid artery surgery, 90 patients who underwent carotid endarterectomy were studied. Transcranial Doppler was performed preoperatively with digital compression of the carotid artery and intraoperatively at the time of cross-clamping, together with routine EEG monitoring. The percentage residual middle cerebral artery velocity (%MCAV) during carotid artery compression or cross-clamping was considered. The intraoperative %MCAV at cross-clamping was compared with the values obtained in the preoperative examination during the compression test and with the EEG data; the EEG records were blindly reviewed by a neurologist and divided into three groups: group A, normal; group B, moderate anomalies and group C, major anomalies. There were no significant differences between preoperative %MCAV (compression test) and intraoperative %MCAV (cross-clamping) by separate analysis of the data related to systolic, diastolic and mean velocity. The systolic, diastolic, mean %MCAV and the Gosling index after cross-clamping were then compared with the EEG data: no significant differences were seen between groups A and B; on the other hand, in all patients with major EEG anomalies (group C) the %MCAV at TCD was reduced to 0. In conclusion, preoperative TCD associated with carotid artery compression appears a safe and useful way of identifying patients at risk of cerebral ischaemia during carotid artery cross-clamping. Patients with no residual flow at intraoperative TCD need to be considered as presenting a very high risk of ischaemia and in this group the use of a shunt is mandatory.     

In Search of Biological Markers of High-Risk Carotid Artery Atherosclerotic Plaque: Enhanced LDL Oxidation

++ -oxidized [oxLDL] or malondialdehyde derivatized LDL [MDA-LDL]), that consistently mirrors the occurrence of oxidative modifications in vivo. A statistically significant correlation (r= 0.23, p= 0.039) was found between the degree of carotid stenosis and antiMDA-LDL specific ratio (a parameter that describes the specificity of LDL towards other proteins as target for oxidative modification). A statistically significant correlation was also found between the PU score and antioxLDL IgG (r= 0.32, p= 0.011), antiMDA-LDL IgG (r= 0.25, p= 0.045) and antiMDA-LDL IgG specific ratio (r= 0.38, p= 0.002). None of the classical biochemical parameters (total, LDL and HDL cholesterol and triglycerides) correlated with the above-mentioned plaque characteristics. The results shown, support the use of biological markers of in vivo LDL oxidation (antioxidatively modified LDL autoantibody titers) to evaluate the clinical setting of high-risk carotid atherosclerosis both in screening and in follow-up studies.     

Histological analysis of the periapical tissues of dog deciduous teeth after root canal filling with diferent materials

The problem of finding an ideal material for filling root canals of deciduous teeth has not been solved yet. This fact led to the development of an experiment to histologically analyze the periapical tissue reaction to 3 root canal filling materials. Eighty root canals of dog deciduous anterior teeth from 6 animals, 60 days old, were used in this study. After biomechanical preparation, the root canals were filled with the following materials: slowly resorbable Maisto paste, Sealer 26 with iodoform, L&C paste (calcium hydroxide with olive oil) and as a control group, canals that were prepared but not filled. At thirty days after the treatment the animals were killed and the teeth prepared for histological analysis. The materials were ranked statistically from the best to the worst as follows: a - Maisto paste, b - Sealer 26 with iodoform, c - control group, d - L&C paste. There was significant difference (p = 0.01) only when the results of the other groups were compared with the L&C paste group. It was also observed that L&C paste was not biologically compatible and that the other materials were biocompatible but their resorption was not at the same rate as that of the deciduous teeth roots.     

The relationship between bone mineral density and periodontitis in postmenopausal women

BACKGROUND: Systemic bone loss has been proposed as a risk factor for periodontal disease; however, the relationship between these two diseases is still not clear. The objective of this study was to assess the relationship between systemic bone mineral density and periodontal disease, controlling for known confounders. METHODS: The study population included 70 postmenopausal Caucasian women aged 51 to 78 (mean +/- SD: 62.10 +/- 7.1 years). Skeletal bone mineral density (BMD) was assessed by dual energy x-ray absorptiometry (DXA) at the neck, trochanter, intertrochanter, Ward's triangle, and total regions of the femur, and from the anterior-posterior view of the lumbar spine. Periodontal disease severity was represented by clinical attachment loss (CAL) and interproximal alveolar bone loss (ABL). Other measures of periodontal status included probing depth (PD), supragingival plaque, gingival bleeding on probing, and calculus. DXA and oral examinations were performed by calibrated examiners. Partial correlation coefficients (r) were obtained from multiple linear regression analysis adjusting for age, age at menopause, estrogen supplementation, cigarette smoking, body mass index, and supragingival plaque. RESULTS: Mean ABL was significantly correlated with BMD of the trochanter (r =- 0.27), Ward's triangle (r = -0.26), and total regions of the femur (r = -0.25). Mean CAL appeared to be related to BMD consistently at all regions of the skeleton, although the association did not reach statistical significance. CONCLUSIONS: We can conclude that skeletal BMD is related to interproximal alveolar bone loss and, to a lesser extent, to clinical attachment loss, implicating postmenopausal osteopenia as a risk indicator for periodontal disease in postmenopausal Caucasian women.     

Clinical and microbial evaluation of a histatin-containing mouthrinse in humans with experimental gingivitis: a phase-2 multi-center study

OBJECTIVE: P-113, a 12 amino acid histatin-based peptide, was evaluated in a mouthrinse formulation for safety and efficacy in a phase 2 multi-center clinical study. METHOD: 294 healthy subjects abstained from oral hygiene procedures and self-administered either 0.01% P-113, 0.03% P-113 or placebo mouthrinse formulations twice daily over a 4-week treatment period. During this time, the safety, anti-gingivitis, and anti-plaque effects of P-113 were evaluated. RESULTS: There was a significant reduction in the change from baseline to Day 22 in bleeding on probing in the 0.01% P-113 treatment group of the intent to treat population (p=0.049). Non-significant trends in the reduction of the other parameters were observed in this population (p> or =0.159). A sub-group of subjects which developed significant levels of disease within the four-week timeframe of the study was identified based on baseline gingival index scores > or =0.75. Significant findings were observed for bleeding on probing, gingival index and plaque index within this population (p<0.05). There were no treatment-related adverse events, and there were no adverse shifts in supragingival microflora during the study. Significant amounts of the peptide were retained in the oral cavity following rinsing. CONCLUSION: These data suggest that P-113 mouthrinse is safe and reduces the development of gingival bleeding, gingivitis and plaque in the human experimental gingivitis model.