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.

An inherited mitochondrial DNA mutation remodels inflammatory cytokine responses in macrophages and in vivo in mice

Impaired mitochondrial bioenergetics in macrophages promotes hyperinflammatory cytokine responses, but whether inherited mtDNA mutations drive similar phenotypes is unknown. Here, we profiled macrophages harbouring a heteroplasmic mitochondrial tRNAAla mutation (m.5019A>G) to address this question. These macrophages exhibit combined respiratory chain defects, reduced oxidative phosphorylation, disrupted cristae architecture, and compensatory metabolic adaptations in central carbon metabolism. Upon inflammatory activation, m.5019A>G macrophages produce elevated type I interferon (IFN), while exhibiting reduced pro-inflammatory cytokines and oxylipins. Mechanistically, suppression of pro-IL-1β and COX2 requires autocrine IFN-β signalling. IFN-β induction is biphasic: an early TLR4-IRF3 driven phase, and a later response involving mitochondrial nucleic acids and the cGAS-STING pathway. In vivo, lipopolysaccharide (LPS) challenge of m.5019A>G mice results in elevated type I IFN signalling and exacerbated sickness behaviour. These findings reveal that a pathogenic mtDNA mutation promotes an imbalanced innate immune response, which has potential implications for the progression of pathology in mtDNA disease patients

Early diagnosis of prostate cancer in the Western Cape

The original publication is available at http://www.samj.org.zaCITATION: Heyns, C.F. et al. 2001. Early diagnosis of prostate cancer in the Western Cape. South African Medical Journal, 91(8):679-684.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. In 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 1 056 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%. In 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. In 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.Publisher’s versio

Stir bar sorptive extraction and gas chromatography : mass spectrometry for the analysis of biological matrices

Thesis (PhD (Chemistry and Polymer Science))--University of Stellenbosch, 2007.This study describes the development of simplified analytical methods for the analysis of trace quantities of selected naturally occurring target compounds in complex biological matrices by stir bar sorptive extraction (SBSE) and gas chromatography/mass spectrometry (GC/MS). SBSE facilitates the direct extraction of organic compounds from aqueous samples by allowing the solutes to partition between the aqueous phase and a glass stir bar that is coated with a layer of polydimethylsiloxane (PDMS). The partitioning of polar compounds into the PDMS coating was enhanced by using different derivatization techniques in combination with SBSE. The derivatization of polar functional groups was performed with ethyl chloroformate, acetic acid anhydride, and O-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine directly in the aqueous samples. Headspace derivatization of compounds containing a secondary alcohol group was performed directly on the stir bar coating in the presence of acetic acid anhydride vapors. The derivatized compounds were thermally desorbed (TD) and analyzed on-line by GC/MS. A number of experimental parameters, including salt addition, temperature and time were optimized to improve the recovery of the derivatized compounds by SBSE. The optimized methods were validated in terms of linearity, precision, and detection and quantitation limits prior to performing the quantification. Trace levels of tuberculostearic acid, a marker of tuberculosis, was detected in sputum samples that were decontaminated and concentrated before being analyzed by SBSE-TD-GC/MS. The method is sufficiently sensitive to detect the marker without the need to culture the organisms, namely M. Tuberculosis. The analysis of 4-hydroxynonenal has also been demonstrated by detecting trace levels of this oxidative stress marker in urine samples obtained from healthy volunteers. Furthermore, abnormally low testosterone/epitestosterone ratios were detected in a group of HIV positive patients by means of SBSE-TD-GC/MS. Further research is required to determine the clinical significance of this finding in the context of HIV infection. Finally, the excessive urinary excretion of estrone and 17β-estradiol following the administration of a high dose of the conjugated equine estrogens to a female volunteer has also been demonstrated