Background: Recent studies suggest that the percentage of TILs is a predictive factor for response to NAC and a prognostic factor associated with long-term disease control in hormone receptor-negative breast cancer. The TILs working group's current recommendation is to evaluate stromal TILs as the principal parameter in future studies. The term lymphocyte-predominant breast cancer (LPBC) can be used as a descriptive term for tumors that contain more lymphocytes than carcinoma cells. Typically, the threshold of stromal lymphocytes for LPBC is around 50% of the stromal surface area. It is unclear if this cutoff will be used in the future as such an intense TIL infiltration in tumors has been reported to be infrequent (∼10%). Studies with TNBC have demonstrated increasingly better overall survival (OS) and disease-free survival (DFS) associated with continuous scores of TIL in patients treated with adjuvant chemotherapy. In patients treated with NAC, TILs predicted pathological complete response (pCR). Our goal was to evaluate the impact of TIL on OS in TNBC patients treated with NAC. Methods: Data from patients with histologically confirmed TNBC treated with NAC from a single institution (A. C. Camargo Cancer Center - ACCCC), between July 2002 and November 2013, were retrospectively collected using electronic medical records. Patients with metastatic disease or in situ carcinoma at diagnosis were excluded. The density of TILs was evaluated in full-face hematoxylin and eosin-stained (HE) slides. Three blinded pathologists made the assessment of each slide, and a consensus on the TIL percentage was achieved. A cut-off of 10% for TIL percentage was employed for OS and DFS calculations, based on technical statistical maximizing log-rank test. We use this cut-off to test the association with pathological pCR rate as well. For pCR rate, we also used a cut-off of 50% (LPBC). We used Chi-square test to evaluate the association with pCR. A p-value<0,05 was considered statistically significant for all tests. Results: We identified 78 patients that fulfilled all inclusion and exclusion criteria. The median age was 42 years (range 17-70), and the clinical stage distribution was IIA (14%), IIB (22%), IIIA (19%), IIIB (33%) and IIIC (11%). 58 patients had archival FFPE blocks available and suitable for pathological analysis. Median follow-up was 4,1 years. Overall survival in 5 years in this subgroup was 62% (median not reached). 23 (39.7%) tumors had TIL> 10%, however only 10 had TIL > 50%. TIL >10% was associated with improved OS (HR 0.33, 95% CI, 1.0 to 0.11; p = 0.04). The same cut-off was associated with better DFS, although not statistically significant (HR 0.46, 95% CI, 1.1 to 0.18; p = 0.1). The overall pCR rate was 39.6% (48% for patients with TIL > 10% and 34% for patients with TIL <or = 10%; p = 0.3). LPBC had similar pCR rate (40% for LPBC vs. 39% for non-LPBC), probably due to the small number of samples analyzed. pCR was associated with a decreased risk of death (HR 0.06, 95% CI, 0.008 to 0.47; p<0.01). Conclusion: We observed improved OS associated with TIL>10% in TNBC patients treated with NAC. pCR was also associated with better OS. Citation Format: Sampaio CdDAT, de Lima VCC, de Andrade VP, Neotti T, Tavares MC, Sessa VA, Calsavara VF, Zenun GR, Giongo AA, da Costa AABA. Tumor-infiltrating lymphocytes (TILs) is associated with improved overall survival in triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy (NAC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-44.
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Objectives: In the treatment of acute myocardial infarction (MI), the time delay to achieve reperfusion of the infarction-related artery has been linked to survival rates. Primary or direct angioplasty has been found to be an excellent means of achieving reperfusion in acute ST-elevation MI compared to thrombolytic therapy in randomized trials. However, no mortality benefit of primary angioplasty over thrombolysis was observed in several registries, in which delays in performing primary angioplasty were longer. Our objectives were to evaluate the door-to-balloon time (DBT) in our institution and investigate its relationship with clinical and prognostic variables. Methods:We studied, retrospectively, 67 patients submitted to primary angioplasty, from January 1999 to November 2000. We divided our patient population into two groups. Group A (GA) included patients with DBT less than 120 min and group B (GB) patients with DBT greater or equal to 120 min. We evaluated several clinical variables, such as left ventricular ejection fraction (LVEF) on their first echocardiogram during hospitalization, admission Killip classification, in-hospital length of stay (LOS) and major cardiovascular events (MACE) during hospitalization and up to 6-month follow-up (in 23 patients). Results:The median DBT was 132 min and the mean was 165 min, with a standard deviation of 137 min for all the cases. We had 32 patients in the GA and 35 patients (52%) in the GB. We observed four in-hospital deaths, all in GB. The mean LVEF was 53.1 ± 9% in GA and 46.1 ± 13% in GB (P = 0.059). Admission Killip class greater than 1 was noted in three patients of each group. The in-hospital LOS was similar for both groups (GA = 8.35 ± 4 and GB = 8.33 ± 4 days; NS). In-hospital events occurred in eight patients of GA (25%) and seven patients of GB (20%; NS). Only five follow-up events occurred during the first 6 months, three events in GA patients and two in GB patients (NS). Conclusion:DBT greater than or equal to 2 h are common and in our population it occurred in more than half of the primary angioplasties. Greater than 2 h DBTs were associated with a trend to larger left ventricular dysfunction early after MI. Monitoring and measures to reduce DBT are crucial for the potential prognosis improvement offered by primary angioplasty and for the broadening of its use in the management of acute MI. P2Primary angioplasty versus streptokinase in elderly patients with acute myocardial infarction PF Leite, M Park, VS Kawabata, MS Barduco, S Timerman, LF Cardoso, JAF Ramires Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil Because only a few studies about acute myocardial infarction (AMI) include elderly patients, we compared outcomes of patients aged 70 years or older with AMI who underwent thrombolysis or primary angioplasty treatment. Methods:From April 1995 to June 1999, 64 patients within 12 h of symptom onset and no contraindications for thrombolytic therapy were randomized in two groups. Group I (32 patients, 20 men) sub...
Objective To examine the effects of short-term cyclic stretch on apoptosis in alveolar type II cells (A549). To study in vitro the direct influence of alveolar type II cells on mechanical stretch. Methods A549 were treated with different doses of lipopolysaccharide (LPS), 0 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml, 1000 ng/ml, and then A549 were lengthened 5%, 15%, 30% using a FLEXCELL tension unit 4000, a vacuum-driven device that applies strain to cells, which were cultured in six-well plates coated with collagen-I, and 12 cycles/min for 4 hours. Apoptosis was measured using the flow cytometry method that measures annexin V and propidium iodide (PI) staining. The morphological changes of apoptotic cells were observed by transmission electron microscope. Results Apoptosis could be induced in alveolar type II cells (A549) by mechanical stretch. The percentage of annexin V + PI cells increased after being treated with cyclic stretch for 4 hours by 5%, 15%, 30% in all groups. The morphological features of apoptotic cells demonstrated by transmission electron microscope were as follows: shrinkage of the cell, chromatin condensation and aggregation under the nuclear membrane as a crescent or lump, membrane-encapsulated nuclear fragment or cell organ formed by invagination of the cell membrane, and apoptotic body formation followed by vacuolization. Conclusion Apoptosis induced by mechanical stretch and LPS is dose dependent. Mechanical stretch aggravates apoptosis especially in cells treated with LPS. Annexin V and PI double staining is a specific, sensitive, and quantitative method for analyzing apoptotic cells. It is also helpful to clarify the protective mechanism of low-volume ventilation in ARDS. Acknowledgement The study was funded by the 'One Hundred People' project of Shanghai Sanitary Bureau (03-77-20). Introduction Although extrapulmonary ALI/ARDS is a common clinical entity, most animal models used to study this disease are induced by direct lung injuries. Our intention was therefore to investigate whether a condition resembling ALI/ARDS develops during the course of a fecal peritonitis in pigs; in that case experimental peritonitis would also prove as a clinically relevant ARDS model. Methods In 10 anesthetized, mechanically ventilated, and instrumented pigs fecal peritonitis was induced by inoculating autologue feces pellets suspended in saline. Mechanical ventilation was set with VT = 8 ml/kg, FiO 2 to reach a SaO 2 target of >90%, PEEP = 10 cmH 2 O if PaO 2 /FiO 2 > 300 and 12 cmH 2 O if PaO 2 /FiO 2 < 300, and respiratory rate to obtain a PaCO 2 of 35-45 mmHg. Before as well as 12 and 24 hours after peritonitis induction we measured the PaO 2 /FiO 2 ratio, the total compliance of the respiratory system (C), calculated as VT/(P plateau -PEEP) and inspiratory airway resistance (R i ) calculated as (P max -P plateau ) / mean inspiratory flow. Data are mean [range]. Results For data see Table 1. During the course of the 24-hour study period, six of 10 animals developed gas exchange deteriorations consistent w...
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