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Aim To gain an understanding of the impact of COVID-19 on the daily life, healthcare needs, mental wellbeing and outlook of patients with Interstitial Lung Disease (ILD) and their caregivers. Methods ILD patients and caregivers were invited to participate in a quantitative survey. Respondents could self-select to then participate in in-depth structured telephone interviews. Survey data was compared to Department of Health COVID-19 public opinion tracker findings for the comparable time period. Results There were 170 survey respones (111 patients and 59 caregivers) and 14 in-depth interview participants. 32% (n=36) of patients and 42% (n=25) of caregivers expressed extreme worry regarding COVID-19 on a 1-10 scale. 83% (n=92) of patients expressed concern about safe hospital access, 33% (n=37) had received a telephone consultation with their clinician, 43% (n=48) reported test delays, 47% (n=52) were exercising less, 23% (n=26) reported worse sleep and 15% (n=17) reported being financially worse off. Carers reported that sleep was worse for 58% (n=34), 42% (n=25) reported being worse off financially, and 40% (n=24) reported a worse diet. Worry (66%, n=39), stress (51%, n=30), anxiety (49%, n=29) were commonly reported by carers. Discussion ILD patients and caregivers reported higher levels of worry regarding COVID-19 compared to the general public. Alternative pathways for quality ILD patient care and interventions to reduce the burden of care on ILD caregivers are required.
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COVID-19/psicologia , Cuidadores/psicologia , Doenças Pulmonares Intersticiais/psicologia , Qualidade de Vida/psicologia , Estresse Psicológico/psicologia , Adulto , COVID-19/epidemiologia , Humanos , Doenças Pulmonares Intersticiais/enfermagem , Masculino , Pessoa de Meia-Idade , Avaliação das NecessidadesRESUMO
BACKGROUND: Neoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens. METHODS: This open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research. DISCUSSION: This RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG). TRIAL REGISTRATION: NCT01726452 . Protocol 10-14. Date of registration 06/11/2012.
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Adenocarcinoma/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica/efeitos dos fármacos , Recidiva Local de Neoplasia/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carboplatina/administração & dosagem , Intervalo Livre de Doença , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Junção Esofagogástrica/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Paclitaxel/administração & dosagem , Qualidade de VidaRESUMO
Radial arteries, used in revascularisation surgery, are prone to spasm. We have examined the ability of nitrovasodilators, calcium channel blockers, and K(ATP) channel openers to cause vasodilation, and to attenuate contractions due to depolarisation and receptor activation in radial and mammary arteries used in coronary artery bypass graft surgery. Two to three millimetre rings of artery obtained from patients at surgery were studied in organ baths in vitro. Constriction to KC1 and phenylephrine was examined before and again after treatment of the rings with drug or vehicle. Calcium channel blockers were the only compounds to inhibit contractions to both KC1 and phenylephrine. Sodium nitroprusside attenuated constriction to phenylephrine but not KC1 in both vessels. K(ATP) channel openers similarly attenuated constriction to phenylephrine in radial arteries but were much less effective in mammary arteries. These studies support the continued use of calcium blockers after revascularisation with radial artery but suggest that other classes of drug may be as effective at minimising spasm due to receptor mediated constriction.
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Artéria Torácica Interna/fisiologia , Artéria Radial/fisiologia , Vasoconstrição/efeitos dos fármacos , Vasodilatadores/farmacologia , Adulto , Idoso , Bloqueadores dos Canais de Cálcio/farmacologia , Ponte de Artéria Coronária , Cromakalim/farmacologia , Relação Dose-Resposta a Droga , Humanos , Técnicas In Vitro , Artéria Torácica Interna/efeitos dos fármacos , Pessoa de Meia-Idade , Nicorandil/farmacologia , Nitroprussiato/farmacologia , Fenilefrina/farmacologia , Cloreto de Potássio/farmacologia , Artéria Radial/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
BACKGROUND: Considerable evidence has shown that the use of computational algorithms to combine pretreatment clinical and pathology results can enhance predictions of patient outcome. The aim of this study was to prove that the application of such methods to predict patient-specific likelihoods of organ-confined (OC) prostate carcinoma (PCA) may be helpful to patients and physicians when they are choosing an optimal treatment for carcinoma of the prostate. METHODS: The authors used clinical and quantitative pathology results from the biopsy specimens of 817 PCA patients who had been evaluated at a large national pathology reference laboratory. The pathology parameters that were measured included the number of positive cores, Gleason grades and score, percentage of tumor involvement, and the tumor location. The pathologic stage of these cases, as determined by results from radical prostatectomy, lymphadenectomy, or bone scan, categorized the PCA as either OC, non-OC due to capsular penetration only (NOC-CP) or advanced disease with metastasis (NOC-Mets), i.e., seminal vesicle and/or lymph-node positive or bone-scan positive. There were a total of 481 OC cases, 185 NOC-CP cases, and 151 NOC-Mets cases. Patient-specific prediction models were trained by ordinal logistic regression (OLOGIT) and genetically engineered neural networks (GENNs), and the resulting trained models were validated by biopsy information from an independent set of 116 PCA patients. RESULTS: When the authors applied a cutoff of >or= 35% for the n = 817 training set of OC, NOC-CP, and NOC-Mets predictive probabilities, the OLOGIT model predicted OC PCA with an accuracy of 91%, whereas the GENN model predicted the same with an accuracy of 95%. When the authors employed the n = 116 validation set (76 OCs, 31 NOC-CPs, and 9 NOC-Mets), the OLOGIT and GENN models correctly identified OC PCA with 91% and 97% accuracy, respectively. CONCLUSIONS: The value of combining patient pretreatment diagnostic pathology parameters to make predictions concerning the postoperative extent of pathology was illustrated clearly in this study. This finding further confirms the need to pursue such approaches for PCA disease management in the future, especially with the increasing prevalence of clinical T1c (American Joint Committee on Cancer, 1977) disease.
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Biópsia , Estadiamento de Neoplasias/métodos , Neoplasias da Próstata/patologia , Humanos , Masculino , Modelos Teóricos , Análise de RegressãoRESUMO
OBJECTIVES: To assess the diagnostic performance of complexed prostate-specific antigen (cPSA), total PSA (tPSA), and calculated free/total PSA (f/t PSA) ratios in the differentiation of benign disease from prostate cancer (CaP) using a contemporary patient cohort. METHODS: The cPSA, tPSA, and calculated fPSA values were determined using the Bayer Immuno-1 system. To validate our calculated f/t PSA ratio, we also retrospectively measured fPSA using the Abbott AxSYM immunoassay system in archival pretreatment sera obtained between 1990 and 1997 from 362 men with clinically and biopsy-confirmed benign prostatic hyperplasia (n = 179) or CaP (n = 183). The diagnostic utility of tPSA, cPSA, and the calculated f/t PSA ratio was assessed using a contemporary test population consisting of sera prospectively collected between June 1999 and June 2000 from 3006 men who had recently undergone a systematic biopsy by urologists in clinical practices throughout the United States. This contemporary patient sample had biopsy diagnoses of either no evidence of malignancy (n = 1857) or CaP (n = 1149). All serum samples had tPSA values between 2.0 and 20.0 ng/mL. RESULTS: The measured versus calculated f/t PSA ratios had a Pearson's correlation coefficient of 0.9130 in the retrospectively studied population of 362 men. The areas under the receiver operating characteristic curves (ROC-AUCs) for the measured and calculated f/t PSA ratios were indistinguishable (69.6% versus 69.2%, respectively). In the contemporary population (n = 3006), the ROC-AUC for tPSA, cPSA, and the calculated f/t PSA ratio was 52.2%, 53.9%, and 58.4%, respectively. We also compared the diagnostic performance using published cutoffs for tPSA (greater than 4.0 ng/mL), cPSA (greater than 3.8 ng/mL), and the f/t PSA ratio (greater than 15% and greater than 25%) in tPSA reflex ranges of 2 to 20 ng/mL and 2 to 10 ng/mL. We found that both cPSA and the f/t PSA ratio (greater than 25% cutoff) outperformed tPSA and yielded similar results in terms of biopsies spared and cancers missed. CONCLUSIONS: The calculated f/t PSA ratio and cPSA perform equally well in terms of the improvement of specificity in the discrimination of benign disease and CaP. The f/t PSA ratio and cPSA provide clinical benefits over the use of tPSA alone, such as an increased sparing of unnecessary biopsies performed with a manageable degree of risk of delayed cancer detection.
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Antígeno Prostático Específico/sangue , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/diagnóstico , Área Sob a Curva , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/sangue , Neoplasias da Próstata/sangue , Valores de Referência , Análise de Regressão , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: This study was conducted to determine if an incidence of hypodiploidy in urinary specimens is related to seasonal temperature changes. MATERIALS AND METHODS: DNA ploidy was evaluated on 10,846 urinary specimens fixed in buffered alcohol (MOPSO/NaCl + ETOH) and received over a one year period from numerous sites throughout the United States. The percentage of hypodiploid (DNA index < 0.8) cases was evaluated in each month. As a control, DNA ploidy results from 3, 755 prostate biopsies, fixed in 10% neutral buffered formalin, received during the winter and summer months of the same year, were evaluated. RESULTS: The average percentage of hypodiploidy in cytologic specimens during the summer months was 19.6% compared to 5. 4% in the winter and early spring months (range: 20.6-4.8%). The average percentage of hypodiploid cells in histologic specimens was 0.8% for both the summer and winter months (range: 1.73-0.36%). CONCLUSIONS: The rate of hypodiploidy in urinary cytology seems to be temperature related. The hypodiploidy rate of histologic specimens fixed in formalin shows no fluctuation with the seasons.
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DNA/genética , Diploide , Estações do Ano , Urina/citologia , Humanos , Manejo de Espécimes , Temperatura , Urina/químicaRESUMO
OBJECTIVES: A prostate biopsy data base derived from patients referred to private practice urologists was analyzed for the cancer diagnosis rates of the "initial" biopsy and the repeated biopsy performed within 1 year for those patients with a noncancer diagnosis. METHODS: A retrospective analysis assessed 132,426 prostate biopsies received and processed by a single pathology laboratory between March 1994 and September 1998; none had had a previous biopsy processed at this laboratory. Prostate cancer was diagnosed in 50,521 of the patients (38.2%). The remaining 81,905 patients (61.8%) had a noncancer diagnosis of either no evidence of malignancy (NEM), high-grade prostatic intraepithelial neoplasia (HGPIN), small acinar glands suspicious for cancer (suspicious), or suspicious with HGPIN (Susp-HGPIN). We identified 6380 (7.8%) of these "noncancer" patients who underwent a repeated biopsy within 1 year. RESULTS: The incidence of NEM, HGPIN, suspicious, and Susp-HGPIN biopsy diagnoses in the "noncancer" patients (81,905) was 55.3%, 3.7%, 2.5%, and 0.3%, respectively. The rate at which these "noncancer" patients (81,905) underwent a repeated biopsy was 4.8% for patients with a diagnosis of NEM, 26.6% for HGPIN, 40.4% for suspicious, and 47.5% for Susp-HGPIN. The overall cancer diagnosis rate in the repeated biopsy patient sample (6380) was 25.7%. When stratified by the initial biopsy diagnosis, the cancer diagnosis rate for the repeated biopsies was 19.8%, 22.6%, 40.0%, and 53.1%, for the patients with NEM, HGPIN, suspicious, and Susp-HGPIN, respectively. The repeated biopsy diagnosis rates did not vary dramatically when analyzed at 3-month intervals during the 1-year period. Also, a strong correlation (79%) was observed between the number of tissue samples obtained at the initial and repeated biopsy procedures. In a subset of patients with free and total prostate-specific antigen (PSA) results obtained before the repeated biopsy (n = 813), we were able to construct a multivariate logistic regression algorithm using the patients' age, initial biopsy diagnosis, total PSA, and free/total PSA ratio that could predict the likelihood of cancer on the repeated biopsy with an accuracy of 70%. CONCLUSIONS: Men who have an initial noncancerous biopsy diagnosis remain at risk of prostate cancer, especially if the initial diagnosis was suspicious or Susp-HGPIN. These data suggest that the initial biopsy strategy needs to be improved and/or expanded to increase the overall cancer detection rate in the primary biopsy. In addition, combining factors such as the initial biopsy diagnosis, family history, digital rectal examination results, prostate gland volume, age, total PSA, and free/total PSA ratio could provide valuable information for predicting the likelihood of cancer.
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Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , Idoso , Biópsia , Transformação Celular Neoplásica/patologia , Seguimentos , Humanos , Funções Verossimilhança , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Neoplasia Prostática Intraepitelial/patologia , Reoperação , Estudos RetrospectivosRESUMO
beta-catenin plays a fundamental role in the regulation of the E-cadherin-catenin cell adhesion complex. It also functions in growth signalling events, independently of the cadherin-catenin complex, and these signalling pathways are disturbed in colorectal cancer. Mutations in either the APC or beta-catenin genes in colorectal cancer cells result in up-regulation of protein expression and subsequent cytoplasmic and nuclear distribution of beta-catenin. In this study, we examined beta-catenin expression in 47 primary colorectal tumors and the corresponding liver metastases. Immunohistochemical studies demonstrated loss of membranous beta-catenin expression in 26% of primary tumors and 60% of liver metastases and a concomitant increase in cytoplasmic and nuclear staining. Widespread nuclear expression of beta-catenin was found in 64% of primary tumors and 21% of liver metastases. No associations were found between any form of beta-catenin expression and either tumor stage or tumor grade. Cellular distribution of beta-catenin was also examined by detergent extraction and Western blot analysis in 16 primary tumors and 23 liver metastases. This analysis showed that most tumors demonstrated reduced beta-catenin in the cytoskeletal fraction and increased beta-catenin in the cytosolic fraction. Furthermore, 3 liver metastases were found to contain a truncated beta-catenin protein of approximately M(r) 80,000. Immunoprecipitation studies showed that the truncated beta-catenin proteins only bound weakly to E-cadherin and beta-catenin compared with non-truncated beta-catenin. These results demonstrate gross alterations in the cellular distribution of beta-catenin in primary colorectal cancers with metastatic potential, as well as in the metastatic tumors. These changes may be the consequence of APC or beta-catenin gene mutations, or possibly result from a post-translational modification of the E-cadherin-catenin complex.
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Neoplasias do Colo/metabolismo , Proteínas do Citoesqueleto/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Retais/metabolismo , Transativadores , Adulto , Idoso , Western Blotting , Neoplasias do Colo/patologia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/patologia , beta CateninaRESUMO
Mutations in the beta-amyloid precursor protein are strongly associated with some cases of familial Alzheimer's disease. The normal physiological role of beta-amyloid precursor protein in the brain was evaluated in a cross-sectional analysis of mice deficient in beta-amyloid precursor protein. Compared with wild-type control mice the beta-amyloid precursor protein-null mice developed age-dependent deficits in cognitive function and also had impairments in long-term potentiation. In addition, the brains of the beta-amyloid precursor protein-null mice had marked reactive gliosis in many areas, especially in the cortex and hippocampus. A subpopulation of mice (n = 15) died prematurely (between three and 18 months of age). Analysis of another six mice from the same population that were showing weight loss and hypolocomotor activity exhibited a marked reactive gliosis as detected by immunoreactivity for glial fibrillary acidic protein and a profound loss of immunoreactivities for the presynaptic terminal vesicle marker proteins synaptophysin and synapsin and the dendritic marker microtubule-associated protein-2 in many brain areas, but most predominantly in the cortex and hippocampus. These results suggest that normal beta-amyloid precursor protein may serve an essential role in the maintenance of synaptic function during ageing. A compromise of this function of the beta-amyloid precursor protein may contribute to the progression of the memory decline and the neurodegenerative changes seen in Alzheimer's disease.
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Envelhecimento/psicologia , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/deficiência , Transtornos Cognitivos/genética , Modelos Animais de Doenças , Gliose/genética , Potenciação de Longa Duração/genética , Proteínas Associadas aos Microtúbulos/deficiência , Receptores Pré-Sinápticos/química , Sinapsinas/deficiência , Sinaptofisina/deficiência , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/fisiologia , Animais , Aprendizagem da Esquiva , Biomarcadores , Córtex Cerebral/química , Córtex Cerebral/patologia , Proteína Glial Fibrilar Ácida/análise , Hipocampo/química , Hipocampo/patologia , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos KnockoutRESUMO
OBJECTIVES: To evaluate the efficacy of applying an age-specific prostate-specific antigen (PSA) reference range to determine whether prostate biopsies are warranted in men 60 to 69 years of age. We estimated the incidence of clinically significant prostate cancer in men in their sixties with PSA levels of 4.01 to 4.50 ng/mL and normal digital rectal examinations (DRE). METHODS: We reviewed 203 sextant prostate biopsies of men in their sixties with PSA levels of 4.01 to 4.50 ng/mL and normal DRE. Tumors were considered clinically significant if the cancer on biopsy was poorly differentiated (Gleason score of 7 or more), involved more than one core, or included a single focus measuring more than 3 mm. RESULTS: The positive biopsy rate was 31.5%. More than 80% of the cancers detected satisfied criteria that almost always predict clinically significant cancer. Thus, among men in their sixties with PSA levels of 4.01 to 4.50 ng/mL and normal DRE, the risk of detecting clinically significant cancer on biopsy was approximately 25%. CONCLUSIONS: Most nonpalpable cancers detected by sextant biopsies in men 60 to 69 years of age with PSA levels of 4.01 to 4.5 ng/mL are clinically significant. Applying an age-specific PSA reference range that increases the upper limit of normal PSA to 4.5 ng/mL results in the failure to detect a substantial number of clinically significant cancers.
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Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Distribuição por Idade , Idoso , Biópsia por Agulha , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Neoplasias da Próstata/sangueRESUMO
Three of the proteins protecting cells from autologous lysis by complement are: membrane cofactor protein (MCP; CD46), an inhibitor of the membrane attack complex formation (CD59), and decay accelerating factor (DAF; CD55). We have investigated the expression of these proteins in breast and colorectal carcinoma by immunohistochemistry and immunoblotting of breast tissue for CD46. CD46 was consistently and strongly expressed in the epithelial compartment in 26/28 ductal carcinomas of the breast, 9/9 fibroadenomas, and 9/11 cases of control non-neoplastic breast tissue. CD59 showed a similar degree of expression in the fibroadenomas (9/9), but was less strongly expressed in carcinomatous (22/28) and control (5/11) tissues. In marked contrast, no CD55 expression was detected in tissue from 15 ductal carcinomas. Immunoblotting of breast tissue for CD46 showed the same size of the molecule as for lymphocytes. It had however considerably stronger expression in tumour tissue than in non-neoplastic tissue. CD46 and CD59 were either lacking or only weakly expressed in the epithelial component of control colorectal mucosa: 2/15 and 5/15, respectively. In contrast, tissue samples from colorectal adenocarcinomas showed clear staining for both CD59 (10/18) and, more markedly, CD46 (15/18). There was no association between the pattern or intensity of CD46 and CD59 expression and tumour differentiation. As the complement regulatory proteins CD46 and CD59 are also strongly expressed by trophoblast at the feto-maternal tissue interface, these results support the concept that similar mechanisms are employed both by the genetically dissimilar fetus and certain tumours to evade immune attack by their host.
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Antígenos CD/análise , Neoplasias da Mama/imunologia , Antígenos CD55/análise , Antígenos CD59/análise , Neoplasias Colorretais/imunologia , Glicoproteínas de Membrana/análise , Adenocarcinoma/imunologia , Adulto , Idoso , Antígenos CD/sangue , Western Blotting , Mama/imunologia , Carcinoma Ductal de Mama/imunologia , Proteínas do Sistema Complemento , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/imunologia , Feminino , Fibroadenoma/imunologia , Antígenos HLA/análise , Humanos , Imuno-Histoquímica , Mucosa Intestinal/imunologia , Linfócitos/imunologia , Proteína Cofatora de Membrana , Glicoproteínas de Membrana/sangue , Pessoa de Meia-Idade , Células Estromais/imunologiaRESUMO
The focus of this review is to survey pretreatment biopsy and patient-derived information applicable to predicting pathological stage and prognosis of men with a diagnosis of prostate cancer. Various sources of clinical and pathological information that may contribute to building decision support tools (DSTs) for application by the urologist to manage prostate cancer patients are presented. These DSTs use serum biomarkers and objective, well-established, pathology information extracted by experienced pathologists from needle-core tissue samples that describe tumor size, grade, and location. Other valuable data can be derived from the biopsy tissue, such as computer-assisted image cytometry-derived DNA ploidy and nuclear morphometry informatics, as well as select tissue biomarker results that may provide supplemental prognostic information. Also discussed are the technical and clinical limitations of these DSTs with respect to the prediction accuracy. A commercially available pretreatment prediction algorithm (UroScore, Oklahoma City, OK) was applied to predict the disease organ confinement status of the prostate cancer test case. Finally, the authors present existing and future applications of computer-derived computational solutions for incorporating all patient history, clinical laboratory, and pathology information into algorithms that can generate patient-specific predictive probability estimates of stage, recurrence, and progression.
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Neoplasias da Próstata/patologia , Biomarcadores Tumorais/sangue , Biópsia , Núcleo Celular/patologia , DNA de Neoplasias/análise , Humanos , Masculino , Estadiamento de Neoplasias , Redes Neurais de Computação , Prognóstico , Próstata/patologia , Antígeno Prostático Específico/sangueRESUMO
OBJECTIVES: To examine the relationship between positive prostate biopsy rates and age over the range of serum prostate-specific antigen (PSA) concentrations of 4 to 10 ng/mL. METHODS: The rates for adenocarcinoma were calculated for prostate biopsy specimens received at UroCor Inc., Oklahoma City, Oklahoma between April 1995 and June 1997. The selection criteria were as follows: men between 50 and 79 years of age, normal digital rectal examination (DRE), prebiopsy PSA level between 4.01 and 10.0 ng/mL obtained within a 4-month period prior to receipt of biopsy, and no previous prostate biopsy. Five thousand six cases were selected out of 81,545 prostate biopsy specimens submitted by office-based urologists. The rates of positive prostate biopsies were stratified by age in decade increments and by PSA in increments of 1 ng/mL. The P values were calculated by the chi-square test. RESULTS: The patient mean age was 65.8 years. An overall increase in the positive prostate biopsy rate for men between 50 and 79 years of age as serum PSA increases from 4.01 to 10.0 ng/mL (P = 0.047) was found; however, this increase was less significant than the increase found in positive biopsy rates caused by age alone (P <0.0001). CONCLUSIONS: Undetected prostate cancer appears to be a major cause of the increasing serum PSA seen with advancing age.
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Adenocarcinoma/sangue , Adenocarcinoma/patologia , Antígeno Prostático Específico/sangue , Próstata/patologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Fatores Etários , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Palpação , RetoRESUMO
OBJECTIVES: To evaluate pathology trends of 62,537 first-time prostate needle-core biopsies submitted by office-based urologists, processed at a single pathology laboratory. METHODS: Prostate biopsy cases obtained over a 2-year period were assessed. Patient information included age, digital rectal examination (DRE) status, and prostate-specific antigen (PSA) serum levels. Biopsy pathology results included the number of tissue samples per case, Gleason score, presence of Gleason grades 4 or 5, percent of biopsy length with evidence of cancer, number of samples with cancer per biopsy, and determination of DNA ploidy status using microspectrophotometry. RESULTS: Adenocarcinoma, suspicious lesions, and isolated high-grade prostatic intraepithelial neoplasia (PIN) were diagnosed in 38.3%, 2.9%, and 4.1% of the biopsies, respectively. For each serum PSA and age range assessed, the positive biopsy rate and incidence of critical pathologic features increased consistently. The average percentage of biopsy length with evidence of tumor, the percentage of cases with Gleason grades 4 or 5, and the percentage of cases with an abnormal DNA ploidy all decreased significantly over the 2-year period (P <0.01). CONCLUSIONS: The number of tissue cores and anatomic sites (locations) being sampled per biopsy are increasing. The tumor size detected and percentage of cases with Gleason grades 4 and 5 are decreasing. There has been a slight increase in the number of biopsies performed on men younger than 60 years of age and a slight decrease in biopsies performed on men older than 70 years of age. The decline in meaningful pathologic features observed in biopsies over time may be clinically relevant to improved disease management.
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Biópsia por Agulha/tendências , Próstata/patologia , Neoplasias da Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Palpação , Prática Privada , Neoplasias da Próstata/epidemiologia , Estados Unidos , UrologiaRESUMO
OBJECTIVE: To evaluate the ability of computer-assisted quantitative nuclear grading (QNG) using a microspectrophotometer and morphometry software to differentiate Feulgen-stained nuclei captured from normal urothelium, low grade transitional cell carcinoma (LG-TCC) and high grade transitional cell carcinoma (HG-TCC) cytology specimens. STUDY DESIGN: Feulgen-stained nuclei from a series of normal volunteers (urologic disease-free history) and from biopsy-confirmed cases of LG-TCC and HG-TCC were evaluated using a CAS-200 image analysis system. Thirty-eight nuclear morphometric descriptors (NMDs) were measured for each nucleus using a software conversion system. Backwards stepwise logistic regression analysis was applied to assess which of the NMDs contributed to QNG statistical models that could differentiate between nuclei from normals vs. LG-TCC, normals vs. HG-TCC, and LG-TCC vs. HG-TCC. Receiver operating characteristic curves and areas under the curve (AUC), as well as cell classification accuracy, were used to assess these differences. RESULTS: Statistically significant differences (P < .0001) were observed between all three categories. In the LG-TCC vs. normals, the QNG solution model required 16/38 features, with an AUC = 93%, a sensitivity = 85%, specificity = 86%, positive predictive value (PPV) = 87% and negative predictive value (NPV) = 84%. The QNG solution model for normals vs. HG-TCC required 12/38 nuclear features yielding an AUC = 99%, sensitivity = 99%, specificity = 98%, PPV = 98% and NPV = 99%. The QNG solution model for LG-TCC vs. HG-TCC required 17/38 nuclear features, with an AUC = 99%, sensitivity = 96%, specificity = 97%, PPV = 97% and NPV = 96%. CONCLUSION: Computer-assisted QNG cell classifiers based upon the measurement of 38 nuclear features, including size, shape and chromatin organization, are capable of differentiating normal urothelial nuclei from LG-TCC and HG-TCC nuclei as well as LG-TCC from HG-TCC nuclei. The QNG cell classifier has shown conclusively that there are morphometric differences between normal urothelial and LG-TCC nuclei that may not be apparent to the naked eye and that it may be useful in helping the pathologist determine the presence or absence of LG-TCC in bladder cytology specimens.
Assuntos
Carcinoma de Células de Transição/patologia , Núcleo Celular/patologia , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Urológicas/patologia , Carcinoma de Células de Transição/classificação , Carcinoma de Células de Transição/urina , Simulação por Computador , Humanos , Pessoa de Meia-Idade , Modelos Biológicos , Estadiamento de Neoplasias , Reação do Ácido Periódico de Schiff , Valor Preditivo dos Testes , Neoplasias Urológicas/classificação , Neoplasias Urológicas/urina , Urotélio/ultraestruturaRESUMO
OBJECTIVE: To characterize the DNA content pattern in cytologically confirmed polyomavirus (PV)-infected urothelial cells and to compare it with DNA ploidy changes in cytologically diagnosed urothelial dysplasia and high grade transitional cell carcinoma. STUDY DESIGN: We selected 200 bladder cytology specimens consisting of four groups with 50 patients each in the following cytologic categories: (1) no evidence of malignancy or dysplasia (controls), (2) PV, (3) urothelial dysplasia (UD), and (4) high grade transitional cell carcinoma (TCC-HG). For each case, two slides with 25-mm filter imprints were stained, one using the Papanicolaou method and the other using the Feulgen staining method. The DNA index (DI), proliferative activity (S + G2M) and degree of hyperploidy (> 5C) were evaluated using an image analysis system. RESULTS: Using the Wilcoxon rank-sum test, statistically significant differences in the DI were found between the PV and UD groups (P = .008) and between the PV and TCC-HG groups (P < .0001). There was no significant difference in the DI between the PV and control groups. The S + G2M fraction for the PV group significantly differed from the control, UD and TCC-HG groups (all P < .0001). Between all four groups, the degrees of hyperploidy were significantly different as well (all P < .0001). CONCLUSION: Cytologically confirmed PV-infected urothelial cells demonstrated a unique DNA content pattern with mildly elevated proliferative activity and a significantly dispersed hyperploid DNA content pattern. DNA analysis can help to differentiate PV infection from dysplasia and high grade carcinoma.
Assuntos
Carcinoma de Células de Transição/genética , DNA de Neoplasias/análise , DNA/análise , Infecções por Polyomavirus/genética , Polyomavirus , Infecções Tumorais por Vírus/genética , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/patologia , Infecções Tumorais por Vírus/patologia , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia , Urotélio/virologiaRESUMO
PURPOSE: Prostate cancer clinical staging methods and decision support tools were reviewed to assess their accuracy to predict pathological staging results and determine what comprises an appropriate clinical staging evaluation. MATERIALS AND METHODS: The MEDLINE data base was searched and 238 abstracts were obtained. Data were extracted from 142 articles that evaluated the preoperative accuracy of digital rectal examination, prostate specific antigen, prostatic acid phosphatase, systematic biopsy parameters (including Gleason scoring), seminal vesicle biopsy, various imaging studies and pelvic lymphadenectomy versus pathological staging results. The sensitivity, specificity and accuracy rates were calculated and tabulated from the reported data on each method or decision support tools for organ confined, nonorgan confined and lymph node metastatic tumor. RESULTS: Decision support tools based on logistic regression analysis, which combine several statistically independent staging parameters, had greater accuracy than any single clinical staging method alone. The most accurate decision support tools for clinical staging combined digital rectal examination (T stage), systematic biopsy parameters (including Gleason scoring) and prostate specific antigen. CONCLUSIONS: The components that comprise the most accurate decision support tools for clinical staging represent an appropriate staging evaluation for the newly diagnosed prostate cancer patient in 1997. Limited use of radiographic imaging and seminal vesicle biopsy may be indicated in select patients to detect bone metastases, and plan pelvic lymphadenectomy and surgical therapy.
Assuntos
Neoplasias da Próstata/patologia , Biópsia , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Estadiamento de Neoplasias/métodos , Reprodutibilidade dos TestesRESUMO
PURPOSE: We determined whether deoxyribonucleic acid (DNA) ploidy analysis by image analysis cytometry enhances the cytological diagnosis of recurrent transitional cell carcinoma of the bladder. MATERIALS AND METHODS: A retrospective study was performed during a 5-year period to evaluate the cytological diagnosis and DNA ploidy analysis of 469 patients with previously diagnosed superficial transitional cell carcinoma. Cytological and DNA ploidy analysis was performed on 1,034 urine and bladder wash specimens, and the patients were monitored with cystoscopy and biopsies as clinically indicated. Cytology results were classified as normal, atypical, dysplastic or cancerous, and DNA ploidy was defined as normal if the diploid index was 1.2 or less, the S phase+G2M fraction was less than 21% or if there were 3% or less hyperploid cells, or abnormal if there was an increased S phase+G2M fraction, an aneuploid peak on the histogram or tetraploidy or hyperploidy was present. RESULTS: The majority of patients (85 of 88, 97%) with a cytological diagnosis of cancer had an abnormal DNA ploidy, and in 60 of 85 of these patients (71%) recurrence was diagnosed within 6 months. Only 5 of 284 specimens (2%) with normal cytology had abnormal DNA ploidy and 1 of these 5 (20%) heralded transitional cell carcinoma recurrence. However, in 145 patients with atypical cytological findings 29 (20%) with abnormal DNA ploidy had a recurrence, compared to 20 of 391 (5%) with normal DNA ploidy (p < 0.0001). Similarly, in 101 patients with dysplastic cytological findings 39 (39%) with abnormal DNA ploidy had transitional cell carcinoma recurrence compared to 4 of 25 with normal ploidy (p = 0.033). CONCLUSIONS: Abnormal DNA ploidy determined by image analysis significantly enhances the detection of bladder tumor recurrence in patients with atypical or dysplastic cytology but not in those with normal cytology or frank carcinoma on cytological findings.