Overuse of Preoperative Staging of Patients Undergoing Neoadjuvant Chemotherapy for Breast Cancer.

BACKGROUND: Guidelines of the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), and the European Society for Medical Oncology (ESMO) discourage the use of imaging to stage newly diagnosed early breast cancer (stages 1 and 2). This study aimed to evaluate preoperative staging imaging rates among patients with stage 1 or 2 breast cancer treated with neoadjuvant chemotherapy (NAC). METHODS: From a prospectively maintained database, 303 patients with stage 1 or 2 breast cancer who had NAC from 2008 to 2016 were identified. The main outcome measures were the rate and outcomes of staging imaging performed. RESULTS: The mean age of the 303 patients with stage 1 or 2 breast cancer was 51 years (range, 26-87 years). Of these 303 patients, 278 (92.4%) had invasive ductal cancer. 90 (30.2%) had estrogen receptor (ER)-positive disease, 79 (26.5%) had triple-negative disease, and 127 (42.6%) had human epidermal growth factor receptor 2 (HER2)-positive disease. Staging positron emission tomography (PET) or computed tomography (CT) scan was performed for 258 patients (85.2%), brain imaging for 94 patients (31%), bone scans for 117 patients (38.6%), and all three for 48 patients (15.8%). As a result, 15 patients (4.9%) with a positive PET/CT scan were upstaged to stage 4 breast cancer. No difference was observed among the ER-positive (p = 1.000), HER2-positive (p = 0.259), or triple-negative (p = 0.369) receptor profiles of the patients upstaged to stage 4 disease. One patient (1.1%) had positive brain imaging. Five patients (4.3%) had a positive bone scan, and three of these patients (60%) had bone metastasis also shown on the PET/CT scan. CONCLUSION: Despite guideline recommendations, a high rate of preoperative staging imaging is completed for patients with clinical stage 1 or 2 breast cancer who receive NAC, with few positive results.

Small bowel carcinoid: Location isn't everything!

AIM: To investigate the prognostic significance of the primary site of disease for small bowel carcinoid (SBC) using a population-based analysis. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was queried for histologically confirmed SBC between the years 1988 and 2009. Overall survival (OS) and disease-specific survival (DSS) were analyzed using the Kaplan-Meier method and compared using Log rank testing. Log rank and multivariate Cox regression analyses were used to identify predictors of survival using age, year of diagnosis, race, gender, tumor histology/size/location, tumor-node-metastasis stage, number of lymph nodes (LNs) examined and percent of LNs with metastases. RESULTS: Of the 3763 patients, 51.2% were male with a mean age of 62.13 years. Median follow-up was 50 mo. The 10-year OS and DSS for duodenal primaries were significantly better when compared to jejunal and ileal primaries (P = 0.02 and < 0.0001, respectively). On multivariate Cox regression analysis, after adjusting for multiple factors, primary site location was not a significant predictor of survival (P = 0.752 for OS and P = 0.966 DSS) while age, number of primaries, number of LNs examined, T-stage and M-stage were independent predictors of survival. CONCLUSION: This 21-year, population-based study of SBC challenges the concept that location of the primary lesion alone is a significant predictor of survival.

Ex vivo exposure to carbon monoxide prevents hepatic ischemia/reperfusion injury through p38 MAP kinase pathway.

A direct role of carbon monoxide (CO), an effector-signaling molecule during heme oxygenase-1 (HO-1) catalysis of heme, in the protection against hepatic ischemia/reperfusion (I/R) injury needs to be established. This study was designed to determine the effects and downstream mechanisms of CO on cold I/R injury in a clinically relevant isolated perfusion rat liver model. After 24 hours of cold storage, rat livers perfused ex vivo for 2 hours with blood supplemented with CO (300 parts per million) showed significantly decreased portal venous resistance and increased bile production, as compared with control livers perfused with blood devoid of CO. These beneficial effects correlated with improved liver function (serum glutamic oxaloacetic transaminase levels) and diminished histological features of hepatocyte injury (Banff's scores). The CO-mediated cytoprotective effects were nitric oxide synthase- and cyclic guanine monophosphate-independent, but p38 mitogen-activated protein kinase (MAPK)-dependent. Moreover, adjunctive use of zinc protoporphyrin, a competitive HO-1 inhibitor, has shown that exogenous CO could fully substitute for endogenous HO-1 in preventing hepatic I/R insult. This study performed in a clinically relevant ex vivo cold ischemia model is the first to provide the evidence that HO-1-mediated cytoprotection against hepatic I/R injury depends on the generation of, and can be substituted by, exogenous CO. The p38 MAPK signaling pathway represents the key downstream mechanism by which CO prevents the I/R insult. In conclusion, regimens that employ exogenous CO should be revisited, as they may have potential applications in preventing/mitigating I/R injury, and thus expanding the liver donor pool for clinical transplantation.