Serum prostate-specific antigen as surrogate for the Histological diagnosis of Prostate cancer

Introduction. To determine whether there is a cut-off value of serum prostate-specific antigen (PSA) which can be used confidently to make the diagnosis of prostate cancer, thereby obviating the need for biopsy.Patients and methods. During the period October 1991 to March 1998 the Department of Chemical Pathology at Tygerberg Hospital performed a total of 6 733 serum PSA assays on 3960 patients. The histopathological and clinical diagnoses of these patients were obtained from records in the departments of Anatomical Pathology, Urological Oncology and Radiation Oncology. The serum PSA levels were correlated with the histopathology reports, using different PSA cut-off values ranging from 5 to 500 ng/ ml, to calculate the sensitivity, specificity, and positive and negative predictive values of each cut-off value of PSA in predicting the presence of prostate cancer.Results. In total, 3 837 (57%) of the 6 733 serum PSA assays were ≤ 4 ng/ ml, 1 045 (15.5%) of the assays were ≥50 ng/ ml, and 798 (11.9%) were~ 100 ng/ ml. Of the total of 3 960 individual patients, 531 (13.4%) had a serum PSA ≥50 ng/ ml and 423 (10.7%) had a PSA ≥ 100 ng/ ml. A serum PSA of ≥ 30 ng/ml had a positive predictive value (PPV) of 90% at a specificity of 87% and sensitivity of 78%, while a PSA ≥ 60 ng/ ml had a PPV of 98% at a specificity of 98% and sensitivity of 65% for the presence of prostate cancer. The PPV reached 99% at a PSA ≥ 100 ng/ ml and 100% at a PSA ≥ 500 ng/ ml, with a specificity of 99% and 100%, but sensitivity of only 53% and 19%, respectively.Conclusions. A serum PSA ≥ 60 ng/ ml has a PPV of 98% for the presence of adenocarcinoma of the prostate, and may be used as a surrogate for histological diagnosis where facilities for obtaining prostatic biopsies are not readily available, thus decreasing costs and patient morbidity

Early diagnosis of prostate cancer in the Western Cape

Background. Early stage prostate cancer does not cause symptoms, and even metastatic disease may exist for years without causing symptoms or signs. Whereas early stage prostate cancer can be cured with radical prostatectomy or radiotherapy, the prognosis of patients with locally advanced or metastatic cancer is significantly poorer.Objectives. ln view of the high incidence of advanced and therefore incurable prostate cancer seen at the oncology clinic of the Department of Urology, Tygerberg Hospital, we started a prostate clinic with the aim of detecting early stage prostate cancer which is potentially curable. A secondary objective was to investigate the question whether there is a higher incidence of prostate cancer among black African men.Patients and methods. Men aged 50 - 70 years were invited by means of media communications (newspaper and radio) to attend our prostate clinic for a free physical examination, including a digital rectal examination (DRE) and serum prostate specific antigen (PSA) assay. If the DRE was clinically suspicious of malignancy and/ or the serum PSA was > 4 ng/ ml, the patient was appropriately counselled and referred for transrectal ultrasound (TRUS)-guided sextant prostate biopsy.Results. In the period June 1997- September 1999 a total of 1056 men attended the prostate clinic. Biopsies were indicated in 160 cases, and were obtained in 114 (71.3%, i.e. 10.8% of the entire cohort). Prostate cancer was detected on first biopsy in 3.5% of the entire group of men (in 35.9% of those with a clinically abnormal DRE, in 41.3% of those with a serum PSA > 4 ng/ ml and in 88.6% of those with an abnormal DRE and serum PSA > 4 ng/ ml. In the 37 men with prostate cancer, the clinical tumour stage was T1 - 2 in 83.8% and T3- 4 in 16.2%. ln the group of patients with clinical stage T1 - 2 tumours, the treatment was watchful waiting in 62.5% of cases, radiotherapy in 20.8% and radical prostatectomy in 16.7%. Analysis of the data according to race showed that in the group of 47 black men there was a higher percentage of clinically abnormal DRE, PSA > 4 .0 ng/ ml and biopsies showing malignancy, and a higher overall prostate cancer detection rate (8.5%).Conclusions. Our prostate cancer detection rate of 3.5% is slightly lower than that reported in larger studies (4.7%), which may be due to the fact that prostate biopsy was performed in only 71% of those who had an indication for biopsy. ln the men diagnosed with clinically localised prostate cancer, potentially curative treatment was given in only 37.5% of cases. This compares unfavourably with the historical cohort of men seen at our oncology clinic, where 53% received potentially curative treatment, and a large European study where potentially curative treatment was given in 89% of cases. Our finding that black men had a higher percentage of clinically abnormal DRE, PSA > 4.0 ng/ ml and biopsies showing malignancy and a higher overall detection rate of prostate cancer should be interpreted with caution, since black men comprised only 4.5% of our overall study cohort.

Improved diagnostics targeting c-MET in non-small cell lung cancer: expression, amplification and activation?

Background: Several c-MET targeting inhibitory molecules have already shown promising results in the treatment of patients with Non-small Cell Lung Cancer (NSCLC). Combination of EGFR-and c-MET-specific molecules may overcome EGFR tyrosine kinase inhibitor (TKI) resistance. The aim of this study was to allow for the identification of patients who might benefit from TKI treatments targeting MET and to narrow in on the diagnostic assessment of MET. Methods: 222 tumor tissues of patients with NSCLC were analyzed concerning c-MET expression and activation in terms of phosphorylation (Y1234/1235 and Y1349) using a microarray format employing immunohistochemistry (IHC). Furthermore, protein expression and MET activation was correlated with the amplification status by Fluorescence in Situ Hybridization (FISH). Results: Correlation was observed between phosphorylation of c-MET at Y1234/1235 and Y1349 (spearman correlation coefficient r(s) = 0.41;p 0.05). c-MET gene amplification was detected in eight of 214 patients (3.7 %). No significant association was observed between c-MET amplification, c-MET protein expression and phosphorylation. Conclusion: Our data indicate, that neither expression of c-MET nor the gene amplification status might be the best way to select patients for MET targeting therapies, since no correlation with the activation status of MET was observed. We propose to take into account analyzing the phosphorylation status of MET by IHC to select patients for MET targeting therapies. Signaling of the receptor and the activation of downstream molecules might be more crucial for the benefit of therapeutics targeting MET receptor tyrosine kinases than expression levels alone

Physics of Solar Prominences: I - Spectral Diagnostics and Non-LTE Modelling

This review paper outlines background information and covers recent advances made via the analysis of spectra and images of prominence plasma and the increased sophistication of non-LTE (ie when there is a departure from Local Thermodynamic Equilibrium) radiative transfer models. We first describe the spectral inversion techniques that have been used to infer the plasma parameters important for the general properties of the prominence plasma in both its cool core and the hotter prominence-corona transition region. We also review studies devoted to the observation of bulk motions of the prominence plasma and to the determination of prominence mass. However, a simple inversion of spectroscopic data usually fails when the lines become optically thick at certain wavelengths. Therefore, complex non-LTE models become necessary. We thus present the basics of non-LTE radiative transfer theory and the associated multi-level radiative transfer problems. The main results of one- and two-dimensional models of the prominences and their fine-structures are presented. We then discuss the energy balance in various prominence models. Finally, we outline the outstanding observational and theoretical questions, and the directions for future progress in our understanding of solar prominences.Comment: 96 pages, 37 figures, Space Science Reviews. Some figures may have a better resolution in the published version. New version reflects minor changes brought after proof editin

Modeling the Subsurface Structure of Sunspots

While sunspots are easily observed at the solar surface, determining their subsurface structure is not trivial. There are two main hypotheses for the subsurface structure of sunspots: the monolithic model and the cluster model. Local helioseismology is the only means by which we can investigate subphotospheric structure. However, as current linear inversion techniques do not yet allow helioseismology to probe the internal structure with sufficient confidence to distinguish between the monolith and cluster models, the development of physically realistic sunspot models are a priority for helioseismologists. This is because they are not only important indicators of the variety of physical effects that may influence helioseismic inferences in active regions, but they also enable detailed assessments of the validity of helioseismic interpretations through numerical forward modeling. In this paper, we provide a critical review of the existing sunspot models and an overview of numerical methods employed to model wave propagation through model sunspots. We then carry out an helioseismic analysis of the sunspot in Active Region 9787 and address the serious inconsistencies uncovered by \citeauthor{gizonetal2009}~(\citeyear{gizonetal2009,gizonetal2009a}). We find that this sunspot is most probably associated with a shallow, positive wave-speed perturbation (unlike the traditional two-layer model) and that travel-time measurements are consistent with a horizontal outflow in the surrounding moat.Comment: 73 pages, 19 figures, accepted by Solar Physic

Autochthonous heritage languages and social media:writing and bilingual practices in Low German on Facebook

This article analyses how speakers of an autochthonous heritage language (AHL) make use of digital media, through the example of Low German, a regional language used by a decreasing number of speakers mainly in northern Germany. The focus of the analysis is on Web 2.0 and its interactive potential for individual speakers. The study therefore examines linguistic practices on the social network site Facebook, with special emphasis on language choice, bilingual practices and writing in the autochthonous heritage language. The findings suggest that social network sites such as Facebook have the potential to provide new mediatized spaces for speakers of an AHL that can instigate sociolinguistic change

The Evershed Flow and the Brightness of the Penumbra

The Evershed flow is a systematic motion of gas that occurs in the penumbra of all sunspots. Discovered in 1909, it still lacks a satisfactory explanation. We know that the flow is magnetized, often supersonic, and that it shows conspicuous fine structure on spatial scales of 0.2"-0.3", but its origin remains unclear. The hope is that a good observational understanding of the relation between the flow and the penumbral magnetic field will help us determine its nature. Here I review advances in the characterization of the Evershed flow and sunspot magnetic fields from high-resolution spectroscopic and spectropolarimetric measurements. Using this information as input for 2D heat transfer simulations, it has been demonstrated that hot Evershed upflows along nearly horizontal field lines are capable of explaining one of the most intriguing aspects of sunspots: the surplus brightness of the penumbra relative to the umbra. They also explain the existence of penumbral filaments with dark cores. These results support the idea that the Evershed flow is largely responsible for the transport of energy in the penumbra.Comment: 18 pages, to appear in "Magnetic Coupling between the Interior and the Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten, Astrophysics and Space Science Proceedings, Springer, Heidelberg, 200