Complete Axillary Lymph Node Dissection Versus Clinical Follow-up in Breast Cancer Patients with Sentinel Node Micrometastasis: Final Results from the Multicenter Clinical Trial AATRM 048/13/2000

Background

It has been suggested that selective sentinel node (SN) biopsy alone can be used to manage early breast cancer, but definite evidence to support this notion is lacking. The aim of this study was to investigate whether refraining from completion axillary lymph node dissection (ALND) suffices to produce the same prognostic information and disease control as proceeding with completion ALND in early breast cancer patients showing micrometastasis at SN biopsy.

Methods

This prospective, randomized clinical trial included patients with newly diagnosed early-stage breast cancer (T < 3.5 cm, clinical N0, M0) who underwent surgical excision as primary treatment. All had micrometastatic SN. Patients were randomly assigned to one of the two study arms: complete ALND (control arm) or clinical follow-up (experimental arm). Median follow-up was 5 years, recurrence was assessed, and the primary end point was disease-free survival.

Results

From a total sample of 247 patients, 14 withdrew, leaving 112 in the control arm and 121 in the experimental arm. In 15 control subjects (13 %), completion ALND was positive, with a low tumor burden. Four patients experienced disease recurrence: 1 (1 %) of 108 control subjects and 3 (2.5 %) of 119 experimental patients. There were no differences in disease-free survival (p = 0.325) between arms and no cancer-related deaths.

Conclusions

Our results strongly suggest that in early breast cancer patients with SN micrometastasis, selective SN lymphadenectomy suffices to control locoregional and distant disease, with no significant effects on survival.     

Histopathologic and Microbiologic Aspects of Ventilator-associated Pneumonia

Background: The relationship between microbiology and histology in patients with ventilator-associated pneumonia has been sparsely described.

Methods: Twenty-five patients who died in the intensive care unit after their lungs had been mechanically ventilated for 72 h were studied. Twenty of the 25 died with clinical suspicion of pulmonary infection. A total of 375 immediate postmortem pulmonary biopsies were obtained after death and processed for quantitative microbiology and histology. Four evolutionary stages of pneumonia were defined: early, intermediate, advanced, and resolution.

Results: At least one specimen with histologic evidence of pneumonia was found in all but two patients (92%). Histologic pneumonia was a widespread and frequent process (46% of biopsies examined) involving predominantly the lower lobes (55% of all biopsies with pneumonia) and showing different histopathologic stages of progression coexisting in the same lung lobes. Lung cultures were frequently polymicrobial (149 of 375, 40% of the pulmonary biopsy cultures, and 20 of 25, 80% of the cases) and not always yielding the same pathogen (19 microorganisms) when comparing one lung to the other. Histopathology and microbiologic biopsy cultures showed a weak relationship (28% and 49% of species had counts greater or equal to 103 cfu/g in samples without pneumonia from patients with and without prior antibiotic treatment, respectively). Histopathologic evolutionary stages were not associated with any differences in quantitative culture results of pulmonary biopsies, independently of prior administration of antibiotics. Higher bacterial concentrations of biopsy cultures were associated with the absence of prior antibiotic treatment.     

Exercise echocardiography to differentiate dilated cardiomyopathy from ischemic left ventricular dysfunction

OBJECTIVES: Previous studies have shown the usefulness of dobutamine echocardiography to differentiate dilated cardiomyopathy (DC) from ischemic left ventricular dysfunction (ILVD), but no studies have been made using exercise echocardiography (EE). We hypothesized that most patients with DC have some contractile reserve and experience an increase in left ventricular ejection fraction (LVEF) during exercise, as opposed to patients with ILVD. Differences in response to EE may be useful to clinically differentiate between these two entities. PATIENTS AND METHOD: Between 1 March 1995 and 1 March 2001, we performed 4,133 EE studies on 3,830 patients. Of 289 patients (8%) with moderate or severe LV dysfunction (biplane LVEF < 41% and left ventricular end-diastolic diameter > 5.2 cm), 207 were excluded: 111 for a history of myocardial infarction; 28 for scarring on echocardiography (regional akinesia/dyskinesia with thinning and/or increased brightness); 13 for previous revascularization procedures; 9 for aortic valve disease; 11 for a known cause of cardiomyopathy; and 35 for not undergoing angiography. The study group was therefore composed of 82 patients who were encouraged to perform maximal treadmill EE. EE criteria for ILVD were either impaired regional wall motion (RWM) or a decrease/no change in LVEF from baseline to peak exercise, while criteria for DC were RWM improvement/no change and LVEF increase. The ILVD group was formed by 39 patients with stenosis >/= 70% diameter stenosis of a major epicardial coronary artery or major branch vessel. The remaining 43 patients constituted the DC group. RESULTS: The number of coronary risk factors (ILVD 2.0 1.1; DC 1.9 1.1), baseline LVEF (ILVD 30 7; DC 30 8), and exercise-induced angina (ILVD 23%; DC 14%) did not differ between groups (p = NS). ILVD patients achieved less Mets (6.6 3.1 vs 8.3 2.8; p < 0.05), had a lower heart rate x systolic blood pressure product (22 5 vs 27 7; p < 0.001), and developed regional and/or global LV dysfunction more frequently (79 vs 28%; p < 0.001). Sensitivity, specificity, positive and negative predictive values and global accuracy for ILVD detection were 79% (95% CI: 70-88), 72% (95% CI: 63-81), 72% (95% CI: 63-81), 79% (95% CI: 67-85), and 76% (95% CI: 69-83), respectively. CONCLUSION: Global and/or regional LV function impairment with exercise is accurate in identifying patients with ILVD. This method could reduce the need for invasive procedures.     

Effects of testosterone on behavior, depression, and cognitive function in older men with mild cognitive loss

BACKGROUND: The role of sex hormones in the prevention of cognitive decline is uncertain. Animal studies suggest mechanisms for sex hormones including testosterone to maintain optimal cognitive function. But, there are studies to suggest that endogenous testosterone levels are associated with aggression in men with cognitive impairment. METHODS: In this pilot study, 11 men (mean age 80 +/- 5 years, range 73-87 years) with early cognitive decline and bioavailable testosterone levels below 128 ng/dl (lower limit for adult normal range) were randomized to receive intramuscular testosterone (200 mg every 3 weeks) or placebo for 12 weeks. Outcome measures included sex hormones (testosterone, bioavailable testosterone, sex hormone binding globulin, estradiol, and estrone), Behave AD Questionnaire, Katz Activities of Daily Living, Geriatric Depression Scale, Digit Span, Clock Face Drawing, Clock Face Perception, Verbal Fluency, Trail-Making B, and International Prostate Symptom Score at baseline, 4 weeks, and 10 weeks. RESULTS: All men completed the study. Total and bioavailable testosterone, estrone, and estradiol levels increased in men receiving testosterone, but no changes were detected in men receiving placebo. No significant changes were found in behavior following testosterone supplementation, nor was there evidence of change in depression or activities of daily living. No discernable changes were found in any of the cognitive tests. Symptoms of prostate hyperplasia remained unchanged in the testosterone (6.6 + 5.8 to 5.2 + 3.6; p =.39) and placebo (8.8 + 6.4 to 6.4 + 3.8; p =.15) groups, and prostate-specific antigen levels did not change significantly. CONCLUSION: No significant changes in behavior, function, depression, or cognitive performance occurred following 12 weeks of testosterone replacement in men with low testosterone levels and early-to-moderate cognitive impairment. This pilot work suggests that testosterone can be given to men with early cognitive impairment without significant concern about worsening aggressive or unwanted behaviors.     

A Study of the Effect of Proinflammatory Cytokines on the Epithelial Cells of Smokers,With or Without COPD

IntroductionCigarette smoke is the main cause of inflammation in COPD. The mechanisms that differentiate smokers who develop COPD are diverse. In this study, we analyzed the presence of cytokines in the respiratory secretions of smokers with or without COPD and the secretory properties of the differentiated bronchial epithelium obtained from the individuals themselves after exposure to tobacco smoke.Material and methodsTwenty-seven smokers were studied, 12 of whom had COPD that had not been previously treated with steroids. In 11, samples were obtained by means of induced sputum, and the remaining samples were collected from bronchial aspiration after bronchoscopy. Concentrations of IL8, IL13, and TNFα in the supernatant were determined. The results obtained were compared between individuals with and without COPD, and we studied their relationship with the severity of COPD as expressed by the degree of obstruction, dyspnea, presence of hypersecretion and intensity of smoking. Bronchial epithelial cell cultures were obtained by air–liquid interface in 4 smokers. The samples were exposed to increasing concentrations of cigarette smoke (5%–20%) and the epithelial mRNA expressions of Muc5AC, IL8, and TNFα were determined.ResultsCOPD patients had significantly higher values of IL8 than healthy smokers (41 [22] pM vs 21 [12] pM). The values of IL8 correlated significantly with the severity of the obstruction (r=0.6; P<.05), dyspnea (r=0.45; P<.05) and the presence of hypersecretion. There was no relationship between cytokines and the intensity or duration of the tobacco habit. Cigarette smoke produced a dose-dependent increase in the expression of RNAm for Muc5AC, IL8, and TNFα.ConclusionsThere are differences in cytokine production (fundamentally IL8) between smokers and smokers with COPD which could be explained by the direct action of cigarette smoke on epithelial cells.