Differential diagnosis of CT focal liver lesions using texture features, feature selection and ensemble driven classifiers

The aim of the present study is to define an optimally performing computer-aided diagnosis (CAD) architecture for the classification of liver tissue from non-enhanced computed tomography (CT) images into normal liver (C1), hepatic cyst (C2), hemangioma (C3), and hepatocellular carcinoma (C4). To this end, various CAD architectures, based on texture features and ensembles of classifiers (ECs), are comparatively assessed.

Removal of Limited Nodal Disease in Patients Undergoing Radical Prostatectomy: Long-Term Results Confirm a Chance for Cure

Abstract PURPOSE: In 2003 we reported on the outcomes of 88 patients with node positive disease who underwent radical prostatectomy and pelvic lymph node dissection (median 21 nodes) between 1989 and 1999. Patients with limited nodal disease appeared to have a good chance of long-term survival, even without immediate adjuvant therapy (androgen deprivation therapy and/or radiotherapy). In this study we update the followup in these patients and verify the reported projected probability of survival. MATERIALS AND METHODS: The projected 10-year cancer specific survival probability after the initially reported followup of 3.2 years was 60% for these patients with node positive disease. The outcome has been updated after a median followup of 15.6 years. RESULTS: Of the 39 patients with 1 positive node 7 (18%) remained biochemically relapse-free, 11 (28%) showed biochemical relapse only and 21 (54%) experienced clinical progression. Of these 39 patients 22 (57%) never required deferred androgen deprivation therapy and 12 (31%) died of prostate cancer. All patients with 2 (20) or more than 2 (29) positive nodes experienced biochemical relapse and only 5 (10%) of these 49 experienced no clinical progression. Of these 49 patients 39 (80%) received deferred androgen deprivation therapy. CONCLUSIONS: Biochemical relapse is likely in patients with limited nodal disease after radical prostatectomy and pelvic lymph node dissection, but for 47% of patients this does not imply death from prostate cancer. Patients with 1 positive node have a good (75%) 10-year cancer specific survival probability and a 20% chance of remaining biochemical relapse-free even without immediate adjuvant therapy.

Differentiating atrioventricular nodal reentrant tachycardia from tachycardia via concealed accessory pathway.

Studies analyzing the diagnostic value of 12-lead electrocardiographic criteria differentiating slow-fast atrioventricular nodal reentrant tachycardia (AVNRT) from atrioventricular reentrant tachycardia (AVRT) due to concealed accessory pathway have shown inconsistent results. In 97 patients (50 with AVNRT, 47 with AVRT) 12-lead electrocardiograms (ECGs) were recorded during sinus rhythm and tachycardia (QRS <120 ms). The ECGs were blinded for diagnosis and patient and analyzed independently by 2 electrophysiologists. The studied criteria differentiating AVNRT from AVRT included pseudo-r'/S, the presence of a retrograde P wave, RP interval, ST-segment depression >/=2 mm with the number and location of the affected leads, QRS amplitude, and cycle length alternans.

Left-septal ablation of the fast pathway in AV nodal reentrant tachycardia refractory to right septal ablation.

In more than 95% of patients with atrioventricular nodal reentrant tachycardia (AVNRT), curative treatment can be achieved with selective ablation of the slow pathway in the right-sided septum. We report a patient with typical AVNRT who had failed attempts to perform conventional right septal ablation of the slow as well as of the fast pathway and finally underwent successful ablation of the fast pathway on the left side of the interatrial septum using a transseptal approach.

Loss of TRAIL-receptors is a recurrent feature in pancreatic cancer and determines the prognosis of patients with no nodal metastasis after surgery

INTRODUCTION Agonistic antibodies targeting TRAIL-receptors 1 and 2 (TRAIL-R1 and TRAIL-R2) are being developed as a novel therapeutic approach in cancer therapy including pancreatic cancer. However, the cellular distribution of these receptors in primary pancreatic cancer samples has not been sufficiently investigated and no study has yet addressed the issue of their prognostic significance in this tumor entity. AIMS AND METHODS Applying tissue microarray (TMA) analysis, we performed an immunohistochemical assessment of TRAIL-receptors in surgical samples from 84 consecutive patients affected by pancreatic adenocarcinoma and in 26 additional selected specimens from patients with no lymph nodes metastasis at the time of surgery. The prognostic significance of membrane staining and staining intensity for TRAIL-receptors was evaluated. RESULTS The fraction of pancreatic cancer samples with positive membrane staining for TRAIL-R1 and TRAIL-R2 was lower than that of cells from surrounding non-tumor tissues (TRAIL-R1: p<0.001, TRAIL-R2: p = 0.006). In addition, subgroup analyses showed that loss of membrane staining for TRAIL-R2 was associated with poorer prognosis in patients without nodal metastases (multivariate Cox regression analysis, Hazard Ratio: 0.44 [95% confidence interval: 0.22-0.87]; p = 0.019). In contrast, analysis of decoy receptors TRAIL-R3 and -R4 in tumor samples showed an exclusively cytoplasmatic staining pattern and no prognostic relevance. CONCLUSION This is a first report on the prognostic significance of TRAIL-receptors expression in pancreatic cancer showing that TRAIL-R2 might represent a prognostic marker for patients with early stage disease. In addition, our data suggest that loss of membrane-bound TRAIL-receptors could represent a molecular mechanism for therapeutic failure upon administration of TRAIL-receptors-targeting antibodies in pancreatic cancer. This hypothesis should be evaluated in future clinical trials.

An Ensemble Kalman Filter multi-tracer assimilation: Determining uncertain ocean model parameters for improved climate-carbon cycle projections

An Ensemble Kalman Filter is applied to assimilate observed tracer fields in various combinations in the Bern3D ocean model. Each tracer combination yields a set of optimal transport parameter values that are used in projections with prescribed CO2 stabilization pathways. The assimilation of temperature and salinity fields yields a too vigorous ventilation of the thermocline and the deep ocean, whereas the inclusion of CFC-11 and radiocarbon improves the representation of physical and biogeochemical tracers and of ventilation time scales. Projected peak uptake rates and cumulative uptake of CO2 by the ocean are around 20% lower for the parameters determined with CFC-11 and radiocarbon as additional target compared to those with salinity and temperature only. Higher surface temperature changes are simulated in the Greenland–Norwegian–Iceland Sea and in the Southern Ocean when CFC-11 is included in the Ensemble Kalman model tuning. These findings highlights the importance of ocean transport calibration for the design of near-term and long-term CO2 emission mitigation strategies and for climate projections.

CD8/CD45RO T-cell infiltration in endoscopic biopsies of colorectal cancer predicts nodal metastasis and survival

BACKGROUND AND AIMS: Reliable prognostic markers based on biopsy specimens of colorectal cancer (CRC) are currently missing. We hypothesize that assessment of T-cell infiltration in biopsies of CRC may predict patient survival and TNM-stage before surgery. METHODS: Pre-operative biopsies and matched resection specimens from 130 CRC patients treated from 2002-2011 were included in this study. Whole tissue sections of biopsy material and primary tumors were immunostained for pancytokeratin and CD8 or CD45RO. Stromal (s) and intraepithelial (i) T-cell infiltrates were analyzed for prediction of patient survival as well as clinical and pathological TNM-stage of the primary tumor. RESULTS: CD8 T-cell infiltration in the preoperative biopsy was significantly associated with favorable overall survival (CD8i p = 0.0026; CD8s p = 0.0053) in patients with primary CRC independently of TNM-stage and postoperative therapy (HR [CD8i] = 0.55 (95% CI: 0.36-0.82), p = 0.0038; HR [CD8s] = 0.72 (95% CI: 0.57-0.9), p = 0.0049). High numbers of CD8i in the biopsy predicted earlier pT-stage (p < 0.0001) as well as absence of nodal metastasis (p = 0.0015), tumor deposits (p = 0.0117), lymphatic (p = 0.008) and venous invasion (p = 0.0433) in the primary tumor. Infiltration by CD45ROs cells was independently associated with longer survival (HR = 0.76 (95% CI: 0.61-0.96), p = 0.0231) and predicted absence of venous invasion (p = 0.0025). CD8 counts were positively correlated between biopsies and the primary tumor (r = 0.42; p < 0.0001) and were reproducible between observers (ICC [CD8i] = 0.95, ICC [CD8s] = 0.75). For CD45RO, reproducibility was poor to moderate (ICC [CD45i] = 0.16, ICC [CD45s] = 0.49) and correlation with immune infiltration in the primary tumor was fair and non-significant (r[CD45s] = 0.16; p = 0.2864). For both markers, no significant relationship was observed with radiographic T-stage, N-stage or M-stage, indicating that assessment of T-cells in biopsy material can add additional information to clinical staging in the pre-operative setting. CONCLUSIONS: T-cell infiltration in pre-operative biopsy specimens of CRC is an independent favorable prognostic factor and strongly correlates with absence of nodal metastasis in the resection specimen. Quantification of CD8i is highly reproducible and allows superior prediction of clinicopathological features as compared to CD45RO. The assessment of CD8i infiltration in biopsies is recommended for prospective investigation.

IMRT with ¹⁸FDG-PET\CT based simultaneous integrated boost for treatment of nodal positive cervical cancer

BACKGROUND To evaluate toxicity and outcome of intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the positive lymph nodes in patients with loco-regional advanced cervical cancer (LRACC). METHODS The study population comprised ten patients with 18FDG-PET\CT positive lymph nodes (LNs), who underwent chemoradiation with IMRT and SIB. A dose of 50.4 Gy, in daily fractions of 1.8 Gy, was delivered to primary tumor and draining LNs. Primary tumor received an additional external beam boost to a total dose of 55.8 Gy. A SIB of 62 Gy, in daily fractions of 2 Gy, was delivered to the 18FDG-PET\CT positive LNs. Finally, a high dose rate brachytherapy (HDRB) boost (15 - 18 Gy) was administered to the primary tumor. The primary goal of this study was to evaluate acute and early late toxicity and loco-regional control. RESULTS The median number of irradiated LNs per patient was 3 (range: 1-6) with a median middle nodal SIB-volume of 26.10 cm3 (range, 11.9-82.50 cm3). Median follow-up was 20 months (range, 12 to 30 months). Acute and late grade 3 toxicity was observed in 1 patient. Three of the patients developed a recurrence, one in the form of a local tumor relapse, one had a paraaortic LN metastasis outside the treated volume and the last one developed a distant metastasis. CONCLUSION IMRT with SIB in the region of 18FDG-PET positive lymph nodes appears to be an effective therapy with acceptable toxicity and might be useful in the treatment of patients with locally advanced cervical cancer.

Transient Earth system responses to cumulative carbon dioxide emissions: linearities, uncertainties, and probabilities in an observation-constrained model ensemble

Information on the relationship between cumulative fossil CO2 emissions and multiple climate targets is essential to design emission mitigation and climate adaptation strategies. In this study, the transient response of a climate or environmental variable per trillion tonnes of CO2 emissions, termed TRE, is quantified for a set of impact-relevant climate variables and from a large set of multi-forcing scenarios extended to year 2300 towards stabilization. An  ∼ 1000-member ensemble of the Bern3D-LPJ carbon–climate model is applied and model outcomes are constrained by 26 physical and biogeochemical observational data sets in a Bayesian, Monte Carlo-type framework. Uncertainties in TRE estimates include both scenario uncertainty and model response uncertainty. Cumulative fossil emissions of 1000 Gt C result in a global mean surface air temperature change of 1.9 °C (68 % confidence interval (c.i.): 1.3 to 2.7 °C), a decrease in surface ocean pH of 0.19 (0.18 to 0.22), and a steric sea level rise of 20 cm (13 to 27 cm until 2300). Linearity between cumulative emissions and transient response is high for pH and reasonably high for surface air and sea surface temperatures, but less pronounced for changes in Atlantic meridional overturning, Southern Ocean and tropical surface water saturation with respect to biogenic structures of calcium carbonate, and carbon stocks in soils. The constrained model ensemble is also applied to determine the response to a pulse-like emission and in idealized CO2-only simulations. The transient climate response is constrained, primarily by long-term ocean heat observations, to 1.7 °C (68 % c.i.: 1.3 to 2.2 °C) and the equilibrium climate sensitivity to 2.9 °C (2.0 to 4.2 °C). This is consistent with results by CMIP5 models but inconsistent with recent studies that relied on short-term air temperature data affected by natural climate variability.