Combination of SELDI-TOF-MS and data mining provides early-stage response prediction for rectal tumors undergoing multimodal neoadjuvant therapy

OBJECTIVE: We investigated whether proteomic analysis of the low molecular weight region of the serum proteome could predict histologic response of locally advanced rectal cancer to neoadjuvant radiochemotherapy (RCT). SUMMARY BACKGROUND DATA: Proteomic analysis of serum is emerging as a powerful new modality in cancer, in terms of both screening and monitoring response to treatment. No study has yet assessed its ability to predict and monitor the response of rectal cancer to RCT. METHODS: Sequential serum samples from 20 patients undergoing RCT were prospectively collected. Time points sampled were as follows: pretreatment, 24/48 hours, 1 week, 2 weeks, 3 weeks, 5 weeks (last day of RCT), and presurgery. Response to treatment was measured using a 5-point tumor regression grade (TRG) based on the degree of residual tumor to fibrosis. All serum samples were analyzed in duplicate using surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS). Support vector machine (SVM) analysis of spectra was used to generate a predictive algorithm for each time point based on proteins that were maximally differentially expressed between good and poor responders. This algorithm was then tested using leave-one-out cross validation. RESULTS: In total, 230 spectra were generated representing all available time points from 9 good responders (TRG 1+2) and 11 poor responders (TRG 3-5). SVM analysis indicated that changes within the serum proteome at the 24/48 hours time point into treatment provided optimal classification accuracy. In more detail, a cohort of 14 protein peaks were identified that collectively differentiated between good and poor responders, with 87.5% sensitivity and 80% specificity. CONCLUSIONS: Serum proteomic analysis may represent an early response predictor in multimodal treatment regimens of rectal cancer. These data suggest that this novel, minimally invasive modality may be a useful adjunct in the multimodal management of rectal cancer, and in the design of future clinical trials.     

Automated image analysis in histopathology: a valuable tool in medical diagnostics

Virtual pathology, the process of assessing digital images of histological slides, is gaining momentum in today's laboratory environment. Indeed, digital image acquisition systems are becoming commonplace, and associated image analysis solutions are viewed by most as the next critical step in automated histological analysis. Here, we document the advances in the technology, with reference to past and current techniques in histological assessment. In addition, the demand for these technologies is analyzed with major players profiled. As there are several image analysis software programs focusing on the quantification of immunohistochemical staining, particular attention is paid to this application in this review. Oncology has been a primary target area for these approaches, with example studies in this therapeutic area being covered here. Toxicology-based image analysis solutions are also profiled as these are steadily increasing in popularity, especially within the pharmaceutical industry. Reinforced by the phenomenal growth of the virtual pathology field, it is envisioned that the market for automated image analysis tools will greatly expand over the next 10 years.     

Giant left atrial myxoma in an elderly patient: natural history over a 7-year period

We present the case of a 71-year-old woman with a 7-year history of a giant left atrial myxoma. The myxoma was attached to the atrial septum and occupied almost the entire left atrial cavity. The patient was hospitalized 4 times because of dyspnea on exertion, palpitations, fatigue, general asthenia, and weight loss. During prior hospitalizations, the patient had refused cardiac surgery. She developed several complications, including atrial fibrillation, mitral and tricuspid regurgitation, mesenteric embolism, pulmonary edema, and thrombotic stroke. We herein describe the natural history of left atrial myxoma in an elderly patient over a 7-year period.     

Left and right ventricular diastolic functions in patients with rheumatoid arthritis without clinically evident cardiovascular disease

The aim of this study was to assess the prevalence of diastolic dysfunction of the left ventricle (LV) and of the right ventricle in patients with rheumatoid arthritis (RA) without clinically evident cardiovascular manifestations and to estimate whether there is a correlation between the duration of RA and the degree of LV diastolic dysfunction. The study included 81 patients (61 females and 20 males) with RA without clinically evident heart disease (group 1) and 40 healthy subjects (29 females and 11 males) who served as a control group (group 2). Both groups were matched for age and sex. Echocardiographic and Doppler studies were conducted in all patients with RA and control subjects. There were significant differences between patients with RA vs. control group with regard to early diastolic flow velocity (E), atrial flow velocity (A) and the E/A ratio (0.68 +/- 0.19 m/s vs. 0.84 +/- 0.14 m/s, p < 0.001; 0.73 +/- 0.15 m/s vs. 0.66 +/- 0.13 cm/s, p = 0.01; and 0.97 +/- 0.3 vs. 1.32 +/- 0.37, p < 0.001, respectively). There was significant difference between groups regarding the right ventricular early diastolic (Er)/atrial (Ar) flow velocities (Er/Ar ratio) (1.07 +/- 0.3 vs. 1.26 +/- 0.3, p = 0.002). There was a weak correlation between transmitral E/A ratio and the duration of RA (r = - 0.22, p = 0.001). Myocardial performance index (MPI) appeared to differ little in patients with RA as compared with control group (0.51 +/- 0.1 vs. 0.52 +/- 0.2, p = NS). In patients with RA without clinically evident cardiovascular disease, the left ventricular diastolic function and the right ventricular diastolic function are reduced. Left ventricular wall thickness, dimensions, systolic function and MPI were found to be normal. LV diastolic function had a weak correlation with the duration of RA.