Prostate cancer in patients with screening serum prostate specific antigen values less than 4.0 ng/dl: results from the cooperative prostate cancer tissue resource

PURPOSE: Prostate cancer can occur in patients with low screening serum prostate specific antigen (PSA) values (less than 4.0 ng/ml). It is currently unclear whether these tumors are different from prostate cancer in patients with high PSA levels (greater than 4.0 ng/ml). MATERIALS AND METHODS: From the Cooperative Prostate Cancer Tissue Resource database through March 2004, 3,416 patients with screening PSA less than 16.0 ng/ml diagnosed with prostate cancer between 1993 and 2004 were stratified in groups based on screening serum PSA. These subsets were compared for race, age at diagnosis, clinical and pathological stage, Gleason score, positive surgical margins, posttreatment recurrent disease, and vital status. RESULTS: We identified 468 (14%) patients with screening PSA less than 4.0 ng/ml, 142 (4.2%) of whom had a PSA of less than 2.0 ng/ml. This group included 40 black and 376 white patients. Men with low screening PSA treated with radical prostatectomy had smaller cancers, lower Gleason scores, lower pathological tumor (T) stage and lower PSA recurrence rates than men with high PSA levels (4 ng/ml or greater). These differences held true for men who were younger than 62 years or were white, whereas older or black men had tumor characteristics and outcomes similar to those with higher PSA levels. CONCLUSIONS: Young (younger than 62 years) or white patients with screening serum PSA less than 4.0 ng/ml had smaller, lower grade tumors and lower recurrence rates than patients with PSA 4.0 ng/ml or greater. This was not true for those older than 62 years and for black men.     

Low density neutrophils in patients with systemic lupus erythematosus, rheumatoid arthritis, and acute rheumatic fever

Ficoll-Hypaque density gradient preparations of peripheral blood mononuclear cells from patients with systemic lupus erythematosus, rheumatoid arthritis, and acute rheumatic fever were highly "contaminated" with low buoyant density neutrophils. Plasma from these patients could induce an in vitro decrease of buoyancy in neutrophils with normal buoyant density. Similar change could be induced by complement-activated sera and aggregated gamma globulin. These data suggest that activated neutrophils are a common finding in the peripheral blood of these patients and may influence the interpretation of any studies with these cells. Functional studies of lymphocytes separated by Ficoll-Hypaque gradients should also take into account the higher degree of impurity of the cell preparations in patients with rheumatic diseases.     

Prostate-specific antigen expression and lipochrome pigment granules in the differential diagnosis of prostatic adenocarcinoma versus seminal vesicle-ejaculatory duct epithelium.

BACKGROUND: Lipochrome pigment granules (LPGs) and prostate-specific antigen (PSA) localization have been cited as helpful adjuncts in differentiating atypical histologic patterns of seminal vesicle-ejaculatory duct (SVED) from prostatic adenocarcinoma. However, LPGs have been described in both benign and neoplastic prostatic acini, and PSA expression within the intraprostatic SVED has not been fully explored. DESIGN: Fifty radical prostatectomy specimens were studied for LPGs and 9 cases for PSA expression. RESULTS: Two morphologic types of LPGs (type 1 and type 2) were observed. The reproducibility in classifying LPGs was evaluated by kappa statistics, which demonstrated a strong agreement between 4 observers. Type 1 was restricted to SVED in all 50 specimens. Type 2 was subclassified into 2A and 2B. Type 2 LPGs were observed in prostatic acini of different zones, high-grade prostatic intraepithelial neoplasia, prostatic adenocarcinoma, and occasionally with type 1 LPG in SVED. Focal reactivity for PSA in the distal portion of SVED near urethra was noted in 1 of 9 cases. CONCLUSION: Awareness about morphologic differences between the 2 types of LPGs could help to avoid a potential diagnostic pitfall of misinterpreting SVED epithelium for adenocarcinoma. Caution is recommended in interpreting PSA expression, since rare focal PSA reactivity was observed in the distal SVED.     

Identification of Heavy Drinkers Using a Combination of Laboratory Tests

Objective: This study derived and evaluated a model that used results of commonly performed laboratory tests to identify men who are heavy drinkers. Method: The results of 40 commonly available laboratory tests were obtained on a diverse sample of 426 heavy drinkers and 188 light drinkers. A logistic regression equation for identifying heavy drinkers was derived in a training data set of 411 subjects and tested in a validation data set of 203 subjects. Results: Ten laboratory measurements were included in the final regression equation: chloride, sodium, ratio of direct to total bilirubin level, blood urea nitrogen, high density lipoproteins, monocyte count, phosphorus, platelets, aspartate aminotransferase, and mean corpuscular hemoglobin. In the validation data this model correctly identified 98% of the 161 heavy drinkers and 95% of the 42 light drinkers. Other models reported in previous literature were applied to these subjects and did not perform as well. The model performed better for subjects of lower socioeconomic status. Conclusions: The laboratory tests in our model may help identify heavy drinkers. The performance of models to identify heavy drinkers depends on the demographic characteristics of the subjects.     

Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung.

BACKGROUND: The majority of lung carcinoma cases occur in current or former smokers. K-ras gene mutations are common in lung adenocarcinoma and have been associated with cigarette smoking, asbestos exposure, and female gender. METHODS: In the current study, the authors examined the contribution of cigarette smoking to K-ras gene mutations in patients with primary lung adenocarcinoma. Smoking histories were obtained from 106 prospectively enrolled patients with primary adenocarcinoma of the lung. RESULTS: K-ras mutations were detected in the primary tumor using an allele-specific ligation assay. Ninety-two of the 106 patients (87%) with lung adenocarcinoma were smokers. Nonsmokers with this tumor were more likely to be women (11 of 14; 79%), whereas the majority of smokers (57%) were men. K-ras mutations were detected in 40 of 106 tumors (38%) and were significantly more common in smokers compared with nonsmokers (43% vs. 0%; P = 0.001). CONCLUSIONS: The results of the current study confirm and extend previous observations that smokers with adenocarcinoma of the lung are more likely to have K-ras mutant tumors compared with nonsmokers. The strong link between cigarette smoking and K-ras mutations in adenocarcinoma of the lung supports the role of specific tobacco carcinogens in the etiology of this malignancy.     

Year in review 2005: Critical Care - resource management

During 2005 Critical Care published several original papers dealing with resource management. Emphasis was placed on sepsis, especially the coagulation cascade, prognosis and resuscitation. The papers highlighted important aspects of the pathophysiology of coagulation and inflammation in sepsis, as well as dealing with the proper use of newly developed compounds. Several aspects of prognosis in critically ill patients were investigated, focusing on biological markers and clinical indexes. Resuscitation received great attention, dealing with the effects of fluid infusion in hemodynamics and the lung. The information obtained can be used to address unknown effects of established therapies, to enlighten current clinical discussion on controversial topics, and to introduce novel medical resources and strategies. Future clinical work will rely heavily on these preclinical and laboratory data.     

Estrogen-initiated transformation of prostate epithelium derived from normal human prostate stem-progenitor cells

The present study sought to determine whether estrogens with testosterone support are sufficient to transform the normal human prostate epithelium and promote progression to invasive adenocarcinoma using a novel chimeric prostate model. Adult prostate stem/early progenitor cells were isolated from normal human prostates through prostasphere formation in three-dimensional culture. The stem/early progenitor cell status and clonality of prostasphere cells was confirmed by immunocytochemistry and Hoechst staining. Normal prostate progenitor cells were found to express estrogen receptor α, estrogen receptor β, and G protein-coupled receptor 30 mRNA and protein and were responsive to 1 nm estradiol-17β with increased numbers and prostasphere size, implicating them as direct estrogen targets. Recombinants of human prostate progenitor cells with rat urogenital sinus mesenchyme formed chimeric prostate tissue in vivo under the renal capsule of nude mice. Cytodifferentiation of human prostate progenitor cells in chimeric tissues was confirmed by immunohistochemistry using epithelial cell markers (p63, cytokeratin 8/18, and androgen receptor), whereas human origin and functional differentiation were confirmed by expression of human nuclear antigen and prostate-specific antigen, respectively. Once mature tissues formed, the hosts were exposed to elevated testosterone and estradiol-17β for 1-4 months, and prostate pathology was longitudinally monitored. Induction of prostate cancer in the human stem/progenitor cell-generated prostatic tissue was observed over time, progressing from normal histology to epithelial hyperplasia, prostate intraepithelial neoplasia, and prostate cancer with local renal invasion. These findings provide the first direct evidence that human prostate progenitor cells are estrogen targets and that estradiol in an androgen-supported milieu is a carcinogen for human prostate epithelium.     

Transcriptional characterizations of differences between eutopic and ectopic endometrium

Endometriosis, defined as the presence of endometrial glandular and stromal cells outside the uterine cavity, is a common gynecological disease with poorly understood pathogenesis. Using laser capture microdissection and a cDNA microarray with 9600 genes/expressed sequence tags (ESTs), we have conducted a comprehensive profiling of gene expression differences between the ectopic and eutopic endometrium taken from 12 women with endometriosis adjusted for menstrual phase and the location of the lesions. With dye-swapping and replicated arrays, we found 904 genes/ESTs that are differentially expressed. We validated the gene expression using real-time RT-PCR. We found that the expression patterns of these genes/ESTs correctly classified the 12 patients into ovarian and nonovarian endometriosis. We identified gene clusters that are location-specific. In addition, we identified several biological themes using Expression Analysis Systematic Explorer. Finally, we identified 79 pathways with over 100 genes with known functions, which include oxidative stress, focal adhesion, Wnt signaling, and MAPK signaling. The identification of these genes and their associated pathways provides new insight. Our findings will stimulate future investigations on molecular genetic mechanisms underlying the pathogenesis of endometriosis.