Examination of the exposome in an animal model: The impact of high fat diet and rat strain on local and systemic immune markers following occupational welding fume exposure.

The goal of this study was to investigate the impact of multiple exposomal factors (genetics, lifestyle factors, environmental/occupational exposures) on pulmonary inflammation and corresponding alterations in local/systemic immune parameters. Accordingly, male Sprague-Dawley (SD) and Brown Norway (BN) rats were maintained on either regular (Reg) or high fat (HF) diets for 24wk. Welding fume (WF) exposure (inhalation) occurred between 7 and 12wk. Rats were euthanized at 7, 12, and 24wk to evaluate local and systemic immune markers corresponding to the baseline, exposure, and recovery phases of the study, respectively. At 7wk, HF-fed animals exhibited several immune alterations (blood leukocyte/neutrophil number, lymph node B-cell proportionality)-effects which were more pronounced in SD rats. Indices of lung injury/inflammation were elevated in all WF-exposed animals at 12wk; however, diet appeared to preferentially impact SD rats at this time point, as several inflammatory markers (lymph node cellularity, lung neutrophils) were further elevated in HF over Reg animals. Overall, SD rats exhibited the greatest capacity for recovery by 24wk. In BN rats, resolution of immune alterations was further compromised by HF diet, as many exposure-induced alterations in local/systemic immune markers were still evident in HF/WF animals at 24wk. Collectively, HF diet appeared to have a greater impact on global immune status and exposure-induced lung injury in SD rats, but a more pronounced effect on inflammation resolution in BN rats. These results illustrate the combined impact of genetic, lifestyle, and environmental factors in modulating immunological responsivity and emphasize the importance of the exposome in shaping biological responses.

Pseudorheumatoid nodule: a variant of granuloma annulare?

We present an adult woman with subcutaneous nodules without any signs or symptoms of rheumatoid arthritis. These nodules are believed to be pseudorheumatoid nodules, which are considered a deep form of granuloma annulare. This case is unique because these are typically found in children and have rarely been reported in adults. These nodules are typically asymptomatic and do not require treatment. However, attempts have been made to treat them with intralesional corticosteroids, cryotherapy, or excision. Owing to the fact that this is considered a deep form of granuloma annulare, they are sometimes treated similarly with a combination of monthly rifampin, ofloxacin, and minocycline.

Development and preliminary evaluation of a new screening instrument for atypical odontalgia and persistent dentoalveolar pain disorder.

AIM: To develop and preliminarily evaluate a new screening instrument for atypical odontalgia (AO) or persistent dentoalveolar pain disorder (PDAP). To evaluate the instrument's performance in detecting AO/PDAP amongst a heterogeneous group of orofacial pain conditions and pain-free controls and empirically compare its performance with an established neuropathic screening instrument (S-LANSS), which is the best available standard. METHODS: The study design was cross-sectional; subjects recruited included a convenience sample of pain-free controls (n = 21) and four groups of orofacial pain conditions: AO/PDAP (n = 22); trigeminal neuralgia (n = 21); temporomandibular disorder (n = 41); and acute dental pain (n = 41). The instrument's internal reliability and factor structure were examined alongside its sensitivity and specificity and ROC-determined threshold score. RESULTS: The 9 AO/PDAP-specific items were found to moderately correlate with the S-LANSS (r = 0.58; P < 0.01). The 14-items of the full instrument were examined using exploratory factor analysis and reduced to ten items in a two-factor structure that explained 96% of the variance. This 10-item final instrument had a ROC area of 0.77 (95% CI: 0.67; 0.88), sensitivity of 77% (95% CI: 55; 92%), and specificity of 69% (95% CI: 60; 77%) with an intentionally higher false-positive rate than false-negative rate. In contrast, the S-LANSS exhibited sensitivity of 32% (95% CI: 14;55%) and specificity of 78% (95% CI: 70;85%) with less optimal false-positive versus false-negative rates. CONCLUSION: This preliminary study confirms the new screening instrument for AO/PDAP merits progression to field testing.

Inhalation of iron-abundant gas metal arc welding-mild steel fume promotes lung tumors in mice.

Welding fumes were reclassified as a Group 1 carcinogen by the International Agency for Research on Cancer in 2017. Gas metal arc welding (GMAW) is a process widely used in industry. Fume generated from GMAW-mild steel (MS) is abundant in iron with some manganese, while GMAW-stainless steel (SS) fume also contains significant amounts of chromium and nickel, known carcinogenic metals. It has been shown that exposure to GMAW-SS fume in A/J mice promotes lung tumors. The objective was to determine if GMAW-MS fume, which lacks known carcinogenic metals, also promotes lung tumors in mice. Male A/J mice received a single intraperitoneal injection of corn oil or the initiator 3-methylcholanthrene (MCA; 10 µg/g) and, one week later, were exposed by whole-body inhalation to GMAW-MS aerosols for 4 hours/day x 4 days/week x 8 weeks at a mean concentration of 34.5 mg/m3. Lung nodules were enumerated by gross examination at 30 weeks post-initiation. GMAW-MS fume significantly increased lung tumor multiplicity in mice initiated with MCA (21.86 ± 1.50) compared to MCA/air-exposed mice (8.34 ± 0.59). Histopathological analysis confirmed these findings and also revealed an absence of inflammation. Bronchoalveolar lavage analysis also indicated a lack of lung inflammation and toxicity after short-term inhalation exposure to GMAW-MS fume. In conclusion, this study demonstrates that inhalation of GMAW-MS fume promotes lung tumors in vivo and aligns with epidemiologic evidence that shows MS welders, despite less exposure to carcinogenic metals, are at an increased risk for lung cancer.

Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort.

BACKGROUND: The natural history of prostate cancer is highly variable and difficult to predict accurately. Better markers are needed to guide management and avoid unnecessary treatment. In this study, we validate the prognostic value of a cell cycle progression score (CCP score) independently and in a prespecified linear combination with standard clinical variables, that is, a clinical-cell-cycle-risk (CCR) score. METHODS: Paraffin sections from 761 men with clinically localized prostate cancer diagnosed by needle biopsy and managed conservatively in the United Kingdom, mostly between 2000 and 2003. The primary end point was prostate cancer death. Clinical variables consisted of centrally reviewed Gleason score, baseline PSA level, age, clinical stage, and extent of disease; these were combined into a single predefined risk assessment (CAPRA) score. Full data were available for 585 men who formed a fully independent validation cohort. RESULTS: In univariate analysis, the CCP score hazard ratio was 2.08 (95% CI (1.76, 2.46), P<10(-13)) for one unit change of the score. In multivariate analysis including CAPRA, the CCP score hazard ratio was 1.76 (95% CI (1.44, 2.14), P<10(-6)). The predefined CCR score was highly predictive, hazard ratio 2.17 (95% CI (1.83, 2.57), χ(2)=89.0, P<10(-20)) and captured virtually all available prognostic information. CONCLUSIONS: The CCP score provides significant pretreatment prognostic information that cannot be provided by clinical variables and is useful for determining which patients can be safely managed conservatively, avoiding radical treatment.

Colorectal cancer incidence and mortality disparities in new Mexico.

Background. Previous analyses indicated that New Mexican Hispanics and American Indians (AI) did not experience the declining colorectal cancer (CRC) incidence and mortality rates observed among non-Hispanic whites (NHW). We evaluated more recent data to determine whether racial/ethnic differences persisted. Methods. We used New Mexico Surveillance Epidemiology and End Results data from 1995 to 2009 to calculate age-specific incidence rates and age-adjusted incidence rates overall and by tumor stage. We calculated mortality rates using National Center for Health Statistics' data. We used joinpoint regression to determine annual percentage change (APC) in age-adjusted incidence rates. Analyses were stratified by race/ethnicity and gender. Results. Incidence rates continued declining in NHW (APC -1.45% men, -1.06% women), while nonsignificantly increasing for AI (1.67% men, 1.26% women) and Hispanic women (0.24%). The APC initially increased in Hispanic men through 2001 (3.33%, P = 0.06), before declining (-3.10%, P = 0.003). Incidence rates declined in NHW and Hispanics aged 75 and older. Incidence rates for distant-stage cancer remained stable for all groups. Mortality rates declined significantly in NHW and Hispanics. Conclusions. Racial/ethnic disparities in CRC persist in New Mexico. Incidence differences could be related to risk factors or access to screening; mortality differences could be due to patterns of care for screening or treatment.

Prognostic value of PTEN loss in men with conservatively managed localised prostate cancer.

BACKGROUND: The natural history of prostate cancer is highly variable and difficult to predict. We report on the prognostic value of phosphatase and tensin homologue (PTEN) loss in a cohort of 675 men with conservatively managed prostate cancer diagnosed by transurethral resection of the prostate. METHODS: The PTEN status was assayed by immunohistochemistry (PTEN IHC) and fluorescent in situ hybridisation (PTEN FISH). The primary end point was death from prostate cancer. RESULTS: The PTEN IHC loss was observed in 18% cases. This was significantly associated with prostate cancer death in univariate analysis (hazard ratio (HR)=3.51; 95% CI 2.60-4.73; P=3.1 × 10(-14)). It was highly predictive of prostate cancer death in the 50% of patients with a low risk score based on Gleason score, PSA, Ki-67 and extent of disease (HR=7.4; 95% CI 2.2-24.6; P=0.012) ), but had no prognostic value in the higher risk patients. The PTEN FISH loss was only weakly associated with PTEN IHC loss (κ=0.5). Both PTEN FISH loss and amplification were univariately predictive of death from prostate cancer, but this was not maintained in the multivariate analyses. CONCLUSION: In low-risk patients, PTEN IHC loss adds prognostic value to Gleason score, PSA, Ki-67 and extent of disease.

Surveillance of colorectal cancer screening in new Mexico hispanics and non-Hispanic whites.

The incidence of colorectal cancer (CRC) among Hispanics in the state of New Mexico has increased in the past decade while that among whites has declined significantly. Using the 2006 New Mexico Behavioral Risk Factor Surveillance System (BRFSS) survey, we compared CRC screening among Hispanics and whites by gender to examine the influence of demographic, socioeconomic, preventive health, and clinical measures on the utilization of CRC screening. Although we found no ethnic differences in the prevalence of current breast, cervical and cancer screening, Hispanics were less likely to be current with CRC screening than whites. These differences were observed across a range of socioeconomic and other explanatory measures and in both genders. Hispanics also had a higher prevalence of CRC-related risk factors than whites, including inactivity, obesity, and diabetes, and ranked lower for most socioeconomic measures. Adjusting for healthcare coverage, education, and income in logistic regression models eliminated the Hispanic-white differences in CRC screening among men, and substantially reduced but did not eliminate screening differences among women. Innovative methods are needed to reach Hispanics to raise awareness of and participation in CRC screening. Because many CRC risk factors are potentially modifiable, appropriate cultural and linguistic interventions tailored to specific Hispanic subgroups and aimed at promoting CRC screening and reducing CRC risk factors may decrease ethnic disparities in CRC incidence.

Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort.

BACKGROUND: The natural history of prostate cancer is highly variable and it is difficult to predict. We showed previously that a cell cycle progression (CCP) score was a robust predictor of outcome in a conservatively managed cohort diagnosed by transurethral resection of the prostate. A greater need is to predict outcome in patients diagnosed by needle biopsy. METHODS: Total RNA was extracted from paraffin specimens. A CCP score was calculated from expression levels of 31 genes. Clinical variables consisted of centrally re-reviewed Gleason score, baseline prostate-specific antigen level, age, clinical stage, and extent of disease. The primary endpoint was death from prostate cancer. RESULTS: In univariate analysis (n=349), the hazard ratio (HR) for death from prostate cancer was 2.02 (95% CI (1.62, 2.53), P<10(-9)) for a one-unit increase in CCP score. The CCP score was only weakly correlated with standard prognostic factors and in a multivariate analysis, CCP score dominated (HR for one-unit increase=1.65, 95% CI (1.31, 2.09), P=3 × 10(-5)), with Gleason score (P=5 × 10(-4)) and prostate-specific antigen (PSA) (P=0.017) providing significant additional contributions. CONCLUSION: For conservatively managed patients, the CCP score is the strongest independent predictor of cancer death outcome yet described and may prove valuable in managing clinically localised prostate cancer.

Selecting Processes to Minimize Hexavalent Chromium from Stainless Steel Welding: Eight welding processes/shielding gas combinations were assessed for generation of hexavalent chromium in stainless steel welding fumes.

Eight welding processes/shielding gas combinations were assessed for generation of hexavalent chromium (Cr6+) in stainless steel welding fumes. The processes examined were gas metal arc welding (GMAW) (axial spray, short circuit, and pulsed spray modes), flux cored arc welding (FCAW), and shielded metal arc welding (SMAW). The Cr6+ fractions were measured in the fumes; fume generation rates, Cr6+ generation rates, and Cr6+ generation rates per unit mass of welding wire were determined. A limited controlled comparison study was done in a welding shop including SMAW, FCAW, and three GMAW methods. The processes studied were compared for costs, including relative labor costs. Results indicate the Cr6+ in the fume varied widely, from a low of 2800 to a high of 34,000 ppm. Generation rates of Cr6+ ranged from 69 to 7800 µg/min, and Cr6+ generation rates per unit of wire ranged from 1 to 270 µg/g. The results of field study were similar to the findings in the laboratory. The Cr6+ (ppm) in the fume did not necessarily correlate with the Cr6+ generation rate. Physical properties were similar for the processes, with mass median aerodynamic diameters ranging from 250 to 336 nm, while the FCAW and SMAW fumes were larger (360 and 670 nm, respectively). CONCLUSION: The pulsed axial spray method was the best choice of the processes studied based on minimal fume generation, minimal Cr6+ generation, and cost per weld. This method is usable in any position, has a high metal deposition rate, and is relatively simple to learn and use.

Barriers to colorectal cancer screening: physician and general population perspectives, New Mexico, 2006.

INTRODUCTION: Colorectal cancer (CRC) screening rates are low in New Mexico. We used statewide surveys of primary care physicians and the general population to characterize CRC screening practices and compare perceptions about screening barriers. METHODS: In 2006, we surveyed 714 primary care physicians in New Mexico about their CRC screening practices, beliefs, and perceptions of patient, provider, and system barriers. A 2004 state-specific CRC screening module for the Behavioral Risk Factor Surveillance System (BRFSS) survey asked 3,355 participants aged 50 years or older why they had not ever or had not recently completed a fecal occult blood test (FOBT) or lower endoscopy. RESULTS: The 216 physicians (30% response rate) reported offering screening to a median 80% of their average-risk patients in the past year and estimated that a median 50% were current with screening. They attributed low screening proportions mainly to patient factors (embarrassment, fear of pain, lack of insurance). However, just 51% of physician respondents used health maintenance flow sheets, and only 13% used electronic medical records to identify patients due for CRC screening. The BRFSS respondents most often reported that lack of physician discussion was responsible for not being current with screening (45% FOBT, 34% endoscopy); being asymptomatic was also often cited as an explanation for lack of screening (22% FOBT, 36% endoscopy). CONCLUSION: Physicians and adults in the general population had markedly different perspectives on barriers to CRC screening. Increasing screening may require system supports to help physicians readily identify patients due for CRC testing and interventions to educate patients about the rationale for screening.

Pancreas oxygen persufflation increases ATP levels as shown by nuclear magnetic resonance.

BACKGROUND: Islet transplantation is a promising treatment for type 1 diabetes. Due to a shortage of suitable human pancreata, high cost, and the large dose of islets presently required for long-term diabetes reversal; it is important to maximize viable islet yield. Traditional methods of pancreas preservation have been identified as suboptimal due to insufficient oxygenation. Enhanced oxygen delivery is a key area of improvement. In this paper, we explored improved oxygen delivery by persufflation (PSF), ie, vascular gas perfusion. METHODS: Human pancreata were obtained from brain-dead donors. Porcine pancreata were procured by en bloc viscerectomy from heparinized donation after cardiac death donors and were either preserved by either two-layer method (TLM) or PSF. Following procurement, organs were transported to a 1.5-T magnetic resonance (MR) system for (31)P nuclear magnetic resonance spectroscopy to investigate their bioenergetic status by measuring the ratio of adenosine triphosphate to inorganic phosphate (ATP:P(i)) and for assessing PSF homogeneity by MRI. RESULTS: Human and porcine pancreata can be effectively preserved by PSF. MRI showed that pancreatic tissue was homogeneously filled with gas. TLM can effectively raise ATP:P(i) levels in rat pancreata but not in larger porcine pancreata. ATP:P(i) levels were almost undetectable in porcine organs preserved with TLM. When human or porcine organs were preserved by PSF, ATP:P(i) was elevated to levels similar to those observed in rat pancreata. CONCLUSION: The methods developed for human and porcine pancreas PSF homogeneously deliver oxygen throughout the organ. This elevates ATP levels during preservation and may improve islet isolation outcomes while enabling the use of marginal donors, thus expanding the usable donor pool.

Inhalation vs. aspiration of single-walled carbon nanotubes in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis.

Nanomaterials are frontier technological products used in different manufactured goods. Because of their unique physicochemical, electrical, mechanical, and thermal properties, single-walled carbon nanotubes (SWCNT) are finding numerous applications in electronics, aerospace devices, computers, and chemical, polymer, and pharmaceutical industries. SWCNT are relatively recently discovered members of the carbon allotropes that are similar in structure to fullerenes and graphite. Previously, we (47) have reported that pharyngeal aspiration of purified SWCNT by C57BL/6 mice caused dose-dependent granulomatous pneumonia, oxidative stress, acute inflammatory/cytokine responses, fibrosis, and decrease in pulmonary function. To avoid potential artifactual effects due to instillation/agglomeration associated with SWCNT, we conducted inhalation exposures using stable and uniform SWCNT dispersions obtained by a newly developed aerosolization technique (2). The inhalation of nonpurified SWCNT (iron content of 17.7% by weight) at 5 mg/m(3), 5 h/day for 4 days was compared with pharyngeal aspiration of varying doses (5-20 microg per mouse) of the same SWCNT. The chain of pathological events in both exposure routes was realized through synergized interactions of early inflammatory response and oxidative stress culminating in the development of multifocal granulomatous pneumonia and interstitial fibrosis. SWCNT inhalation was more effective than aspiration in causing inflammatory response, oxidative stress, collagen deposition, and fibrosis as well as mutations of K-ras gene locus in the lung of C57BL/6 mice.

A modified ab externo approach for suture fixation of an intraocular lens implant in the dog.

The goals of canine cataract and lens instability surgery should be to ensure a small incision, minimal tissue trauma, shortened surgical time, maintenance of the anterior chamber, and restoration of emmetropia through the use of a stable intraocular lens specifically designed for the canine eye. While this is usually the case with routine phacoemulsification and in-the-bag intraocular lens implantation, it is often not the case with lens instability, lens luxation or large posterior capsular ruptures. In such cases the incisions are often larger, surgical time and tissue trauma are excessive, and the patient is often left aphakic. The goal of this paper is to present a modified ab externo technique designed to allow removal of the lens and placement of a ciliary sulcus sutured IOL through a small incision, with minimal trauma and shortened surgical time. Use of this technique may allow more canine patients to be emmetropic postoperatively. In addition, the ease of this procedure may encourage earlier removal of an unstable lens and decrease the risk of secondary glaucoma and retinal detachment that occur in association with lens luxation.

The placental bed in pregnancies complicated by primary antiphospholipid syndrome.

UNLABELLED: Pregnancy in women with primary antiphospholipid syndrome (APS) is frequently associated with placental insufficiency leading to intrauterine growth restriction (IUGR)+/-fetal death, pre-eclampsia, placental abruption, premature delivery or thrombosis. The aim of this study was to investigate the placental bed in APS pregnancies for evidence of impaired trophoblast invasion, endothelial cell activation (ECA) and macrophage infiltration. METHODS: Biopsies from the presumed site of the placental bed were obtained from 12 women with treated primary APS and 16 controls. Immunohistochemical methods were employed to investigate expression of cytokeratin (trophoblasts), alpha-actin (smooth muscle), CD68 (macrophages) and VCAM-1 (as marker of ECA). Fibrinoid and elastin distribution and expression were determined by periodic acid/Schiff and orcein stain, respectively. RESULTS: Three APS pregnancies developed IUGR, one with concurrent pre-eclampsia. Eight of 12 APS biopsies were confirmed to be from the placental bed; one patient failed to meet APS criteria and was excluded from analysis; six included spiral arteries in the biopsy; 11 of 16 controls' biopsies were from the placental bed. APS biopsies had a higher concentration of inflammatory cells (p=0.0001), particularly macrophages (p=0.014). Three APS biopsies showed necrosis with hyperplastic vessels; one demonstrated arterial thromboses, but none had profound vasculopathy/atherosis or ECA. CONCLUSION: Inflammatory mechanisms in the placental bed may contribute to APS pregnancy complications.

The effect of combination antiretroviral therapy on CD5 B- cells, B-cell activation and hypergammaglobulinaemia in HIV-1-infected patients.

OBJECTIVES: This study assessed B-cell activation, CD5 B-cells and circulating immunoglobulin levels in HIV-infected patients treated with combination antiretroviral therapy (CART). METHODS: Measurement of plasma immunoglobulin levels and electrophoresis of plasma proteins, and analyses of total numbers of B-cells and B-cells expressing CD 38 and CD5 in whole blood, were undertaken in 47 consecutive HIV-1-infected patients attending an out-patient clinic. RESULTS: All HIV-infected patients had similar percentages and numbers of B-cells. Proportions of CD5 B-cells in all HIV-infected patients were significantly lower than those in HIV-negative controls. Aviraemic HIV-infected patients on CART had lower percentages of CD5, CD 38 and CD5 CD 38 B-cell subsets and lower plasma levels of immunoglobulin G (IgG) and immunoglobulin A (IgA) than viraemic HIV-infected patients (untreated or on CART). However, 33-37% of aviraemic HIV-infected patients had IgG and IgA levels above the 95th percentile of the normal range defined in HIV-seronegative donors. In aviraemic HIV-infected patients, plasma IgA levels correlated only with proportions of activated (CD 38) B-cells. IgG levels did not correlate with the proportions of B-cell subsets or any marker of HIV disease activity. Monoclonal immunoglobulins were not detected in any plasma sample. CONCLUSIONS: Aviraemic HIV-infected patients on CART have lower plasma levels of IgG and IgA than viraemic HIV-infected patients, but levels are often above the normal range. CD5 B-cell numbers are depressed, so these cells are unlikely to contribute to hypergammaglobulinaemia in HIV-infected patients.

Dysregulation of CD28 and CTLA-4 expression by CD4 T cells from previously immunodeficient HIV-infected patients with sustained virological responses to highly active antiretroviral therapy.

OBJECTIVES: Current guidelines recommend commencing highly active antiretroviral therapy (HAART) in HIV-infected patients when CD4 T-cell counts reach 350 cells/microL. However, late-presenting HIV-infected patients with CD4 T-cell counts<50 cells/microL are still common. The ability of long-term HAART to normalize immune dysregulation in severely immunodeficient HIV-infected patients remains unclear. Here we address indices of immune dysregulation in previously severely immunocompromised HIV-infected patients treated with long-term HAART who had achieved increased CD4 T-cell counts and complete suppression of HIV viraemia. METHODS: We examined expression of CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and intracellular perforin by CD4 and CD8 lymphocytes from 25 highly selected HIV-infected patients [nadir CD4 T-cell counts <50 cells/microL, >4 years on HAART and >6 months of complete viral suppression (<50 HIV-1 RNA copies/mL)] and 18 HIV-seronegative age- and sex-matched controls. RESULTS: HIV-infected patients had lower percentages of CD28-expressing CD4 lymphocytes and higher percentages of CTLA-4-expressing CD4 lymphocytes than controls. The percentage of CTLA-4-expressing CD4 lymphocytes correlated inversely with that of CD28-expressing CD4 lymphocytes. The proportion of CD4 lymphocytes expressing perforin was generally low. However, more HIV-infected patients than controls had >1% of CD4 lymphocytes expressing perforin [11 of 25 (44%) vs. one of 18 (5.5%)]. The percentage of CD8 lymphocytes expressing perforin did not differ between HIV-infected patients and controls. Amongst HIV-infected patients, the percentage of perforin-expressing CD8 lymphocytes correlated inversely with nadir but not current CD4 T-cell count. CONCLUSIONS: Expression of CD28, CTLA-4 and perforin by CD4 lymphocytes remain dysregulated in HIV-infected patients with previous severe immunodeficiency, despite increased CD4 T-cell counts and control of HIV viraemia by HAART.

Differences between men with screening-detected versus clinically diagnosed prostate cancers in the USA.

BACKGROUND: The advent of prostate specific antigen (PSA) testing in the United States of America (USA) has led to a dramatic increase in the incidence of prostate cancer in the United States as well as the number of men undergoing aggressive treatment with radical prostatectomy and radiation therapy. We compared patient characteristics and treatment selection between American men with screening-detected versus clinically diagnosed prostate cancers. METHODS: We evaluated 3,173 men with prostate cancer in the USA. Surveys and medical records provided information on demographics, socioeconomic status, comorbidities, symptoms, tumor characteristics, and treatment. We classified men presenting with symptoms of advanced cancer - bone pain, weight loss, or hematuria - as "clinically diagnosed"; asymptomatic men and those with only lower urinary tract symptoms were considered "screening-detected." We used multivariate analyses to determine whether screening predicted receiving aggressive treatment for a clinically localized cancer. RESULTS: We classified 11% of cancers as being clinically diagnosed. Men with screening-detected cancers were more often non-Hispanic white (77% vs. 65%, P < 0.01), younger (36% < 65 years vs. 25%, P or= high school vs. 67%, P < 0.01), healthier (18% excellent health vs. 10%, P < 0.01), and diagnosed with localized disease (90% vs. 75%, P < 0.01). Men with screening-detected localized cancers more often underwent aggressive treatment, 76% vs. 70%, P = 0.05. CONCLUSION: Most cancers were detected by screening in this American cohort. Appropriately, younger, healthier men were more likely to be diagnosed by screening. Minority status and lower socio-economic status appeared to be screening barriers. Screening detected earlier-stage cancers and was associated with receiving aggressive treatment.

New Mexico's capacity for increasing the prevalence of colorectal cancer screening with screening colonoscopies.

INTRODUCTION: Colorectal cancer screening rates are low throughout the United States. Colonoscopy has been recommended as a cost-effective strategy for colorectal cancer screening and prevention. We evaluated New Mexico's capacity to increase the prevalence of colorectal cancer screening using colonoscopy. METHODS: We identified New Mexican gastroenterologists from state licensing data and from endoscopic manufacturers. We surveyed gastroenterologists on their weekly number of colonoscopies, capacity for additional screening colonoscopies, and barriers to increasing capacity. We used census data, published data on the yield of screening colonoscopy, and professional society guidelines for cancer/polyp surveillance to estimate the additional colonoscopies required to increase the state's prevalence of endoscopic screening. RESULTS: Forty gastroenterologists, representing all 11 group practices in the state, and nine of 12 solo practitioners responded. They estimated that their weekly procedure capacity could be increased by 41%, from 832 to 1174 colonoscopies. We estimated an annual capacity increase of 14,880 procedures, which could increase the prevalence of endoscopic colorectal cancer screening from the current 35% to about 50% over five years. Lack of support staff, space, and physicians were barriers to increasing screening. CONCLUSION: Implementing a screening colonoscopy strategy could achieve the goal of a higher level of colorectal screening. However, achieving more universal screening would require additional testing modalities.