Survival and inferential analysis in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and subsequent sentinel lymph node biopsy: prospective single-center study.

BACKGROUND: The lymph node staging is the major prognostic factor in breast cancer patients. Sentinel lymph node biopsy (SLNB) allows an exactly axillar staging in patients with early disease, but not in locally advance breast cancer (LABC). Our aim was to study, the feasibility and accuracy of the SLNB technique with and without axillar lymphadenectomy (LDN) and with lymph node clipping after neoadjuvant chemotherapy (NAC), in patients with LABC. PATIENTS AND METHODS: Patients diagnosed with LABC, scheduled for NAC and subsequent surgery and SLNB. Subsequently the patients were scheduled for adjuvant chemotherapy/hormonotherapy and radiotherapy according with the postsurgical results. Main end points were overall survival (OS) disease-free survival (DFS), mortality, SLNB identification rate (IR), sensitivity, false negative rate (FNR) of SLNB versus LDN, negative predictive value (NPV) and overall accuracy. RESULTS: Our IR with different techniques was between 89.9 and 100%. OS was between 89 and 97%. DFS was between 89.8 and 96.8%. Sensitivity was between 75 and 100%. NPV was between 89.6 and 100%. FNR was between 0 and 25%; and accuracy was between 66 and 72%. We found that survival was lower (p < 0.05) in patients with triple negative and Luminal B/HER2 intrinsic subtype; with progression or major partial response in Magnetic Resonance Imaging (MRI) results at the end of NAC and in patients with BRCA1/2 mutation. CONCLUSIONS: Our study presents excellent results of SLNB alone in patients with LABC with complete nodal response with an OS and DFS > 95%. The FNR is very high in partial responders, so we cannot recommend the SLNB alone in LABC. We recommend, in cN+ patients, axillar clipping, SLNB and LDN because in more than 50% of the patients with axillar clipping, this was not found, and because in 36% of the patients with negative LDN, the SLN (Sentinel Lymph Node) obtained was the only positive node, so these techniques together decrease the FNR and improve the node staging, OS and DFS. This study is the first prospective study that assess OS and DFS in patients with LABC, all submitted to SLNB.

Single dose propranolol does not affect physiologic or emotional reactivity to smoking cues.

BACKGROUND: Smoking cue exposure reactivates salient smoking-related memories, triggering craving to smoke, a phenomenon associated with maintenance of smoking behavior and relapse after periods of abstinence. Acute ß-adrenergic blockade with propranolol reduces physiologic reactivity during subsequent recollection of traumatic events by inhibiting reconsolidation of reactivated memories in a process called memory reconsolidation blockade. OBJECTIVE: The objective of this study is to determine whether a single dose of propranolol prior to retrieval of smoking-related memories reduces subsequent physiologic reactivity to personally salient smoking imagery scripts in current smokers. METHODS: Fifty-four overnight-abstinent, adult smokers received a single-dose propranolol or placebo prior to reactivation of smoking-related memories in a randomized, double-blind, placebo-controlled trial and resumed smoking afterward. One week later, skin conductance (SC), heart rate (HR), left corrugator electromyogram (EMG), self-reported emotional state, and craving were assessed following script-driven imagery with neutral and personalized smoking-related scripts. RESULTS: Smoking scripts were associated with increased physiologic activation (SC, HR, EMG), craving, and negative emotional state compared with neutral scripts. Propranolol did not moderate the effect of script type on any outcome. CONCLUSION: Personalized smoking script-driven imagery robustly increased physiologic activation, negative emotional state, and craving, and a single dose of propranolol prior to memory reactivation did not moderate this effect.

Varenicline for Smoking Cessation in Schizophrenia: Safety and Effectiveness in a 12-Week, Open-Label Trial.

OBJECTIVES: Varenicline was approved by the FDA in 2006. In 2009, based largely on case reports, the FDA issued a warning of possible adverse neuropsychiatric effects including depression and suicidal thoughts and behavior for varenicline and bupropion. Prospective trials of varenicline have not reported increased incidence of psychiatric adverse events other than sleep disturbance, but smokers with major mental illness have been excluded from large prospective trials of varenicline to date. We sought to evaluate the effect of a standard open-label 12-week varenicline trial on prospectively assessed safety and smoking outcomes in stable, treated adults with schizophrenia spectrum disorder and nicotine dependence. METHODS: One-hundred-and-twelve stable outpatients who smoked >10 cigarettes/day participated in a 12-week, open-label, smoking cessation trial of varenicline and weekly group cognitive behavioral therapy. Participants took varenicline for 4 weeks before attempting cessation. Trained raters collected safety and smoking outcome data weekly. RESULTS: Participants demonstrated improved psychotic symptoms, depressive symptoms and nicotine withdrawal symptoms from baseline to week 12 or early termination. At the end of 12 weeks open label treatment, the 14- and 28-day continuous abstinence rates were 47.3 and 34%, respectively. Expired CO declined significantly during treatment in those who did not achieve abstinence. CONCLUSIONS: This prospective study suggests that varenicline may be well-tolerated and effective for smoking cessation in combination with group CBT in stable outpatients with schizophrenia, a group with high rates of smoking and smoking-attributable morbidity and mortality.

A randomized, double-blind, placebo-controlled trial of long-acting risperidone in cocaine-dependent men.

OBJECTIVE: There is no approved pharmaco-therapy for cocaine dependence. Risperidone is an atypical antipsychotic drug with combined dopamine-2/serotonin-2 (D(2)/5-HT(2)) antagonist activity that has been effective in reducing cocaine use in some animal studies. We tested the efficacy of a long-acting, injectable preparation of risperidone on cocaine use in active cocaine users. METHOD: Thirty-one cocaine-dependent men who met DSM-IV diagnostic criteria for current cocaine dependence entered a 12-week, randomized, double-blind, placebo-controlled trial of intramuscular risperidone, 25 mg every other week. The primary outcome measure was cocaine use as measured by urinary concentration of cocaine metabolites. Secondary outcomes were self-report of cocaine use and craving, depressive symptoms as measured by the Hamilton Rating Scale for Depression (HAM-D), and adverse events. Participants were recruited during a 12-month period from October 2005 to September 2006. RESULTS: Both groups reduced their cocaine use during the study. There were no between-group differences in the primary measure of cocaine use (urinary metabolites [F = 0.7, p = .41]) or on craving measures. Those assigned to risperi-done reported significantly worsened depressive symptoms (mean +/- SD HAM-D change scores: +7.4 +/- 8.8 vs. -2.3 +/- 5.8, respectively, F = 7.5, p = .018) and gained significantly more weight (mean weight change: +6.3 +/- 9.4 lb vs. -4.0 +/- 8.9 lb, respectively, F = 4.65, p = .044) than those assigned to placebo. CONCLUSION: Treatment with long-acting injectable risperidone in active cocaine users was not associated with reduction in cocaine use or craving and was associated with worsening of depressive symptoms and weight gain. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00385801.