Comparação entre metodologias de controle de qualidade em mamografia digital

The best way to detect breast cancer is by screening mammography. The mammography equipments are dedicated and require a rigorous quality control in order to have a good quality image and to early detect this disease. The digital equipment is relatively new in the market and there isn’t a national rule for quality control for several types of digital detectors. This study has proposed to compare two different tests manuals for quality control provided by the manufacturers of digital mammography equipments, and also compare them to the “European guidelines for quality assurance in breast cancer screening and diagnosis “(2006). The studied equipments were: Senographe 2000D from General Electric (GE) and the Hologic Selenia Lorad. Both were digital mammography equipments, the GE unit presents an indirect digital system and the other presents a direct digital system. Physical parameters of the image have been studied, such as spatial resolution, contrast resolution, noise, signal-tonoise ratio, contrast-to-noise ratio and modulation transfer function. After that, a study of the importance of quality control and the requirement to implement a Quality Assurance Program has been done. One data collection was done to compare those manual, it was done by checking which tests are indicated and the minimum frequency which they should be conducted in accordance with each manufacturer. The tests were performed by different methodologies and the results were compared. The examined tests were: the breast entrance skin dose, mean glandular dose, contrast-to-noise ratio, signal-to-noise ratio, automatic exposure control and automatic control of density, modulation transfer function, equipment resolution, homogeneity and ghost

Desafios à organização de programa de rastreamento do câncer do colo do útero em Manaus-AM

Objetivou-se identificar as características sociodemográficas das mulheres que realizam o Papanicolaou em Manaus, Amazonas, e sua associação com os motivos para realização do exame. Pesquisa exploratória incluindo 281 mulheres, que haviam realizado o Papanicolaou nos últimos cinco anos em Manaus. A maioria das entrevistadas tinha entre 18-34 anos (54%), 5-11 anos de estudo (54,4%), renda familiar mensal de até três salários mínimos (84,3%), relação estável (72,2%) e início da vida sexual entre 15-19 anos (69,4%). Os motivos para realização do Papanicolaou foram procura espontânea (66,2%), recomendação médica (23,5%) e sintomas ginecológicos (10,3%). Mulheres que receberam informação dos profissionais de saúde tiveram proporção maior de realização do exame nos últimos três anos (p=0,008). A demanda espontânea é prevalente e o atendimento oportunístico é realizado nas mulheres mais jovens, não alcançando o grupo com maior risco para o câncer. É necessário implantar estratégias de recrutamento ativo alcançando mulheres em desvantagem socioeconômica.

Stereotactict body radiotherapy (SBRT)

Purpose: evaluation and comparison of volumetric modulated RapidarcTM radiotherapy (RA-IMRT) vs linac based Stereotactic body radiotherapy (SBRT) in the salvage treatment of isolated lymph node recurrences in patients affected by gynaecological cancer. Materials and Methods From January 2010 to September 2011, 15 patients affected by isolated lymph nodes recurrence of gynaecological cancer underwent salvage radiotherapy after conventional imaging staging with CT and 18-FDG-PET/CT. Two different radiotherapy techniques were used in this study: RA-IMRT (RapidarcTM implemented radiotherapy Varian Medical System, Palo Alto, CA, USA) or SBRT (BrainLAB, Feldkirchen, Germany). Five patients underwent CT scan and all patients underwent 18FDG-PET/CT for pre-treatment evaluation and staging. The mean total dose delivered was 54.3 Gy (range 50-60 Gy with conventional fractionation and 27.4 Gy (range 12-40 Gy hypofractionation) for RA-IMRT and SBRT respectively. The mean number of fractions was 27.6 fractions (range 25-31) and 3-4 fractions , the mean overall treatment duration was 40.5 days (range 36-45) and 6.5 days (range 5-8 days) for RA-IMRT and SBRT respectively. Results: At the time of the analysis, October 2011, the overall survival was 92.3 % (80% for RA-IMRT and 100% for SBRT). Six patients are alive with no evidence of disease and also six patients are alive with clinically evident disease in other sites (40% and 50% patients RA-IMRT vs SBRT respectively, one patient died for systemic progression of disease and two patient were not evaluable at this time. Conclusions: Our preliminary results showed that, the use of RA-IMRT and SBRT are an excellent local therapy for isolated lymph nodes recurrences of gynaecological cancer with a good toxicity profile and local control rate, even if any long term survivors would be expected. New treatment modalities like Cyberknife are also being implemented.

Pre- and posttransplant management of solid organ transplant recipients: risk-adjusted follow-up

Solid organ transplant recipients (SOTR) have an increased risk of skin cancer due to their long-term immunosuppressive state. As the number of these patients is increasing, as well as their life expectancy, it is important to discuss the screening and management of skin cancer in this group of patients. The role of the dermatologist, in collaboration with the transplant team, is important both before transplantation, where patients are screened for skin lesions and the individual risk for skin cancer development is assessed, and after transplantation. Posttransplant management consists of regular dermatological consultations (the frequency depends on different factors discussed below), where early skin cancer screening and management, as well as patient education on sun protective behavior is taught and enforced. Indeed, SOTR are very sensitive to sun damage due to their immunosuppressive state, leading to cumulative sun damage which results in field cancerization with numerous lesions such as in situ squamous cell carcinoma, actinic keratosis and Bowen's disease. These lesions should be recognized and treated as early as possible. Therapeutic options discussed will involve topical therapy, surgical management, adjustment of the patient's immunosuppressive therapy (i.e. reduction of immunosuppression and/or switch to mammalian target of rapamycin inhibitors) and chemoprevention with the retinoid acitretin, which reduces the recurrence rate of squamous cell carcinoma. The dermatological follow-up of SOTR should be integrated into the comprehensive posttransplant care.

The lower quality of preventive care among forced migrants in a country with universal healthcare coverage

OBJECTIVE To assess the association between socio-demographic factors and the quality of preventive care and chronic care of cardiovascular (CV) risk factors in a country with universal health care coverage. METHODS Our retrospective cohort assessed a random sample of 966 patients aged 50-80years followed over 2years (2005-2006) in 4 Swiss university primary care settings (Basel/Geneva/Lausanne/Zürich). We used RAND's Quality Assessment Tools indicators and examined recommended preventive care among different socio-demographic subgroups. RESULTS Overall patients received 69.6% of recommended preventive care. Preventive care indicators were more likely to be met among men (72.8% vs. 65.4%; p<0.001), younger patients (from 71.0% at 50-59years to 66.7% at 70-80years, p for trend=0.03) and Swiss patients (71.1% vs. 62.7% in forced migrants; p=0.001). This latter difference remained in multivariate analysis adjusted for gender, age, civil status and occupation (OR 0.68; 95% CI 0.54-0.86). Forced migrants had lower scores for physical examination and breast and colon cancer screening (all p≤0.02). No major differences were seen for chronic care of CV risk factors. CONCLUSION Despite universal healthcare coverage, forced migrants receive less preventive care than Swiss patients in university primary care settings. Greater attention should be paid to forced migrants for preventive care.

Attitudes of Parents at risk of inheriting Li-Fraumeni Syndrome towards predictive genetic testing in their minor-aged children.

Li-Fraumeni Syndrome (LFS) is a hereditary cancer syndrome which predisposes individuals to cancer beginning in childhood. These risks are spread across a lifetime, from early childhood to adulthood. Mutations in the p53 tumor suppressor gene are known to cause the majority of cases of LFS. The risk for early onset cancer in individuals with Li-Fraumeni Syndrome is high. Studies have shown that individuals with LFS have a 90% lifetime cancer risk. Children under 18 have up to a 15% chance of cancer development. Effectiveness of cancer screening and management in individuals with Li-Fraumeni Syndrome is unclear. Screening for LFS-associated cancers has not been shown to reduce mortality. Due to the lack of effective screening techniques for childhood cancers, institutions vary with regard to their policies on testing children for LFS. There are currently no national guidelines regarding predictive testing of children who are at risk of inheriting LFS. No studies have looked at parental attitudes towards predictive p53 genetic testing in their children. This was a cross-sectional pilot study aimed at describing these attitudes. We identified individuals whose children were at risk for inheriting p53 genetic mutations. These individuals were provided with surveys which included validated measures addressing attitudes and beliefs towards genetic testing. The questionnaire included qualitative and quantitative measures. Six individuals completed and returned the questionnaire with a response rate of 28.57%. In general, respondents agreed that parents should have the opportunity to obtain p53 genetic testing for their child. Parents vary in regard to their attitudes towards who should be involved in the decision making process and at what time and under what considerations testing should occur. Testing motivations cited most important by respondents included family history, planning for the future and health management. Concern for insurance genetic discrimination was cited as the most important “con” to genetic testing. Although limited by a poor response rate, this study can give health care practitioners insight into testing attitudes and beliefs of families considering pediatric genetic testing.

Incidental detection of an occult oral malignancy with autofluorescence imaging: a case report.

BACKGROUND: Autofluorescence imaging is used widely for diagnostic evaluation of various epithelial malignancies. Cancerous lesions display loss of autofluorescence due to malignant changes in epithelium and subepithelial stroma. Carcinoma of unknown primary site presents with lymph node or distant metastasis, for which the site of primary tumour is not detectable. We describe here the use of autofluorescence imaging for detecting a clinically innocuous appearing occult malignancy of the palate which upon pathological examination was consistent with a metastatic squamous cell carcinoma. CASE DESCRIPTION: A submucosal nodule was noted on the right posterior hard palate of a 59-year-old white female during clinical examination. Examination of this lesion using a multispectral oral cancer screening device revealed loss of autofluorescence at 405 nm illumination. An excisional biopsy of this nodule, confirmed the presence of a metastatic squamous cell carcinoma. Four years ago, this patient was diagnosed with metastatic squamous cell carcinoma of the right mid-jugular lymph node of unknown primary. She was treated with external beam irradiation and remained disease free until current presentation. CONCLUSION: This case illustrates the important role played by autofluorescence tissue imaging in diagnosing a metastatic palatal tumour that appeared clinically innocuous and otherwise would not have been biopsied.

Patient and physician gender concordance in preventive care in university primary care settings.

OBJECTIVE To assess the quality of preventive care according to physician and patient gender in a country with universal health care coverage. METHODS We assessed a retrospective cohort study of 1001 randomly selected patients aged 50-80 years followed over 2 years (2005-2006) in 4 Swiss university primary care settings (Basel, Geneva, Lausanne, Zürich). We used indicators derived from RAND's Quality Assessment Tools and examined percentages of recommended preventive care. Results were adjusted using hierarchical multivariate logistic regression models. RESULTS 1001 patients (44% women) were followed by 189 physicians (52% women). Female patients received less preventive care than male patients (65.2% vs. 72.1%, p<0.001). Female physicians provided significantly more preventive care than male physicians (p=0.01) to both female (66.7% vs. 63.6%) and male patients (73.4% vs. 70.7%). After multivariate adjustment, differences according to physician (p=0.02) and patient gender (p<0.001) remained statistically significant. Female physicians provided more recommended cancer screening than male physicians (78.4 vs. 71.9%, p=0.01). CONCLUSIONS In Swiss university primary care settings, female patients receive less preventive care than male patients, with female physicians providing more preventive care than male physicians. Greater attention should be paid to female patients in preventive care and to why female physicians tend to provide better preventive care.

The Spanish translation, cultural adaptation and validation of the Powe Fatalism Inventory

Background/significance. The scarcity of reliable and valid Spanish language instruments for health related research has hindered research with the Hispanic population. Research suggests that fatalistic attitudes are related to poor cancer screening behaviors and may be one reason for low participation of Mexican-Americans in cancer screening. This problem is of major concern because Mexican-Americans constitute the largest Hispanic subgroup in the U.S.^ Purpose. The purposes of this study were: (1) To translate the Powe Fatalism Inventory, (PFI) into Spanish, and culturally adapt the instrument to the Mexican-American culture as found along the U.S.-Mexico border and (2) To test the equivalence between the Spanish translated, culturally adapted version of the PFI and the English version of the PFI to include clarity, content validity, reading level and reliability.^ Design. Descriptive, cross-sectional.^ Methods. The Spanish language translation used a translation model which incorporates a cultural adaptation process. The SPFI was administered to 175 bilingual participants residing in a midsize, U.S-Mexico border city. Data analysis included estimation of Cronbach's alpha, factor analysis, paired samples t-test comparison and multiple regression analysis using SPSS software, as well as measurement of content validity and reading level of the SPFI. ^ Findings. A reliability estimate using Cronbach's alpha coefficient was 0.81 for the SPFI compared to 0.80 for the PFI in this study. Factor Analysis extracted four factors which explained 59% of the variance. Paired t-test comparison revealed no statistically significant differences between the SPFI and PFI total or individual item scores. Content Validity Index was determined to be 1.0. Reading Level was assessed to be less than a 6th grade reading level. The correlation coefficient between the SPFI and PFI was 0.95.^ Conclusions. This study provided strong psychometric evidence that the Spanish translated, culturally adapted SPFI is an equivalent tool to the English version of the PFI in measuring cancer fatalism. This indicates that the two forms of the instrument can be used interchangeably in a single study to accommodate reading and speaking abilities of respondents. ^

The use of culturally related health practices and health care utilization among Hispanic women in farmworker communities

Breast and cervical cancer screening rates continue to be lower in Hispanic women than other ethnic subgroups. Several factors have been identified that influence health care utilization. The use of preventive services (cancer screenings and adherence) in addition to yearly doctor visits are often used to measure health care utilization. A secondary analysis of an existing dataset containing baseline survey data collected from participants of an intervention trial to test the Cultivando La Salud (CLS) program was used to analyze the association between cultural health practice use (use of curandero,s obador, and herbal remedies) and health care utilization. The sample consisted of women 50 years of age and older living in farmer communities in four sites: Eagle Pass, TX, Anthony, NM, Merced, CA, and Watsonville, CA (n=708). Participants reported using a curandero (5.67%), sobador (29.79%), and herbal remedies (46.65%) at some point in their lives. The use of cultural health practices was found to significantly influence utilization of certain health care services: use of herbal remedies influence doctor visits, adherence to mammography screening and adherence to Pap test screening; use of a curandero influenced ever having a mammogram; use of a sobador influenced ever having a mammogram, ever having a Pap test, and Pap test adherence. In addition, women reporting use of curandero or herbal remedies were found to be more avoidant of the health care system than those that reported not using them. Further research is needed to further analyze the influence of cultural health practices on health care utilization. ^

Parental acculturation and adolescent HPV uptake among Hispanics: Results from the California Health Interview Survey

Background. The Centers for Disease Control and Prevention (CDC), the American Cancer Society (ACS), and the American College of Obstetricians and Gynecologists (ACOG) all recommend the HPV vaccine for girls 11-12. The vaccine has the potential to reduce cervical cancer disparities if it is used by populations that do not participate in screening. Evidence suggests that incidence and mortality are higher among Hispanic women compared to non-Hispanic white women because they do not participate in screening. Past literature has found that acculturation has a mixed effect on cervical cancer screening and immunization. Little is known about whether parental acculturation is associated with adolescent HPV vaccine uptake among Hispanics and the mechanisms through which acculturation may affect vaccine uptake.^ Aims. To examine the association between parental acculturation and adolescent HPV uptake among Hispanics in California and test the structural hypothesis of acculturation by determining if socioeconomic status (SES) and health care access mediate the association between acculturation and HPV vaccine uptake.^ Methods. Cross-sectional data from the 2007 California Health Interview Survey (CHIS) were used for bivariate and multivariate logistic regression analyses. The sample used for analysis included 1,090 Hispanic parents, with a daughter age 11-17, who answered questions about the HPV vaccine. Outcome variable of interest was HPV vaccine uptake (≥1dose). Independent variables of interest were language spoken at home (a proxy variable for acculturation), household income (percent of federal poverty level), education level, and health care access (combined measure of health insurance coverage and usual source of care).^ Results. Parents who spoke only English or English and Spanish in the home were more likely to get the HPV vaccine for their daughter than parents who only spoke Spanish (Odds Ratio [OR]: 0.55, 95% Confidence Interval [CI]: 0.31-0.98). When SES and health care access variables were added to the logistic regression model, the association between language acculturation and HPV vaccine uptake became non-significant (OR: 0.68, 95% CI: 0.35-1.29). Both income and health care access were associated with uptake. Parents with lower income or who did not have insurance and a usual source of care were less likely to have a vaccinated daughter.^ Discussion. Socioeconomic status and health care access have a more proximal effect on HPV vaccine uptake than parental language acculturation among Hispanics in California.^ Conclusion. This study found support for the structural hypothesis of acculturation and suggest that interventions focus on informing low SES parents who lack access to health care about programs that provide free HPV vaccines.^

Noninvasive functional optical spectroscopy of human breast tissue

Near infrared diffuse optical spectroscopy and diffuse optical imaging are promising methods that eventually may enhance or replace existing technologies for breast cancer screening and diagnosis. These techniques are based on highly sensitive, quantitative measurements of optical and functional contrast between healthy and diseased tissue. In this study, we examine whether changes in breast physiology caused by exogenous hormones, aging, and fluctuations during the menstrual cycle result in significant alterations in breast tissue optical contrast. A noninvasive quantitative diffuse optical spectroscopy technique, frequency-domain photon migration, was used. Measurements were performed on 14 volunteer subjects by using a hand-held probe. Intrinsic tissue absorption and reduced scattering parameters were calculated from frequency-domain photon migration data. Wavelength-dependent absorption (at 674, 803, 849, and 956 nm) was used to determine tissue concentration of oxyhemoglobin, deoxyhemoglobin, total hemoglobin, tissue hemoglobin oxygen saturation, and bulk water content. Results show significant and dramatic differences in optical properties between menopausal states. Average premenopausal intrinsic tissue absorption and reduced scattering values at each wavelength are 2.5- to 3-fold higher and 16–28% greater, respectively, than absorption and scattering for postmenopausal subjects. Absorption and scattering properties for women using hormone replacement therapy are intermediate between premenopausal and postmenopausal populations. Physiological properties show differences in mean total hemoglobin (7.0 μM, 11.8 μM, and 19.2 μM) and water concentration relative to pure water (10.9%, 15.3%, and 27.3%) for postmenopausal, hormone replacement therapy, and premenopausal subjects, respectively. Because of their unique, quantitative information content, diffuse optical methods may play an important role in breast diagnostics and improving our understanding of breast disease.

Variabilidade intratípica de HPV 16 em relação à origem étnica e HLA de uma população de alto risco para o câncer do colo do útero

A infecção por papilomavirus é a principal causa de desenvolvimento de neoplasias intraepiteliais cervicais (NIC) e câncer do colo do útero (CCU). Estudos epidemiológicos têm demonstrado que a persistência do genoma viral encontra-se associado a variantes moleculares específicas de papilomavirus humano (HPV) de alto risco. As moléculas HLA de classe II têm um importante papel na resposta imune. Associações entre HLA e CCU ou infecção por HPV tem sido demonstrado em diferentes populações. O nosso objetivo foi verificar se a variabilidade de HLA-DRB1 e DQB1 estavam associada ao CCU e NIC III em mulheres de Belém, uma população formada pelos 3 principais grupos étnicos humanos e uma área de alto risco para o CCU no Norte do Brasil. Foi investigada a existência de diferenças na distribuição de alelos HLA entre mulheres com CCU e NIC III portadoras de diferentes variantes de HPV-16 e mulheres citologicamente normais. Os genes HLA DQB1 e DRB1 foram tipados pelo método de PCR-SSO em 95 casos e 287 controles de mulheres com citologia normal atendidas em um centro de prevenção do colo do útero na mesma cidade. As variantes de HPV-16 foram tipadas por sequenciamento de um fragmento da região controladora do genoma viral (LCR). O polimorfismo na posição 350 do gene E6 foi tipado baseado em um protocolo de hibridização em pontos, para identificar a alteração na posição 350T→G. A magnitude das associações foi estimada por odds ratio (OR) e os respectivos intervalos de confiança (IC), ajustados para potenciais fatores de confusão. Uma associação positiva foi observada entre CCU e os haplótipos DRB1* 150 l-DQB1*0602, DRB1*04-DQB1*0301 e DRB1*1602-DQB1*0301. Ao contrário, DRB1*01-DQB1*0501 mostrou um efeito protetor. Os alelos DRB1*0804, DQB1*0402 apresentaram efeito protetor contra positividade por HPV. O alelo DQB1*0502 e o grupo DRB1*15 foram positivamente associados. Os nossos resultados mostram que as associações positivas de DRB1*1501 e DRB1*1602 podem ser atribuídas a variantes asiático-americanas quando comparado a variantes européias. O risco conferido a DRB1*1501 foi encontrado associado tanto a variantes E6350G quanto a variantes E6350T, entretanto, o maior efeito foi devido às variantes E6250T. A associação positiva de DRB1*1602 foi significativa somente no grupo de mulheres positivas para E6350G. Estes resultados estão de acordo com a composição étnica da população estudada bem como um maior potencial oncogênico de certas variantes. Nossos dados sugerem que a contribuição dos alelos HLA na susceptibilidade genética ao CCU difere de acordo com a distribuição das variantes de HPV em uma dada região geográfica ou grupo étnico.

The effect of skin examination surveys on the incidence of basal cell carcinoma in a Queensland community sample: A 10-year longitudinal study

Skin cancers pose a significant public health problem in high-risk populations. We have prospectively monitored basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) incidence in a Queensland community over a 10-y period by recording newly treated lesions, supplemented by skin examination surveys. Age-standardized incidence rates of people with new histologically confirmed BCC were 2787 per 100,000 person-years at risk (pyar) among men and 1567 per 100,000 pyar among women, and corresponding tumor rates were 5821 per 100,000 pyar and 2733 per 100,000 pyar, respectively. Incidence rates for men with new SCC were 944 per 100,000 pyar and for women 675 per 100,000 pyar; tumor rates were 1754 per 100,000 pyar and 846 per 100,000 pyar, respectively. Incidence rates of BCC tumors but not SCC tumors varied noticeably according to method of surveillance, with BCC incidence rates based on skin examination surveys around three times higher than background treatment rates. This was mostly due to an increase in diagnosis of new BCC on sites other than the head and neck, arms, and hands associated with skin examination surveys and little to do with advancing the time of diagnosis of BCC on these sites as seen by a return to background rates following the examination surveys. We conclude that BCC that might otherwise go unreported are detected during skin examination surveys and thus that such skin cancer screening can influence the apparent burden of skin cancer.

The application of aryne chemistry and use of α-diazo carbonyl derivatives in indazole synthesis with biological evaluation

This thesis outlines the synthetic chemistry involved in the preparation of a range of novel indazole compounds and details the subsequent investigation into their potential as biologically active agents. The synthetic route utilised in this research to form the indazole structure was the [3+2] dipolar cycloaddition of diazo carbonyl compounds with reactive aryne intermediates generated in situ. The preparation of further novel indazole derivatives containing different functional groups and substituents was performed by synthesising alternative 1,3- dipole and dipolarophile analogues and provided additionally diverse compounds. Further derivatisation of the indazole product was made possible by deacylation and alkylation methods. Transformation reactions were performed on alkenecontaining ester side chains to provide novel epoxide, aldehyde and tertiary amine derivatives. The first chapter is a review of the literature beginning with a short overview on the structure, reactivity and common synthetic routes to diazo carbonyl derivatives. More attention is given to the use of diazo compounds as 1,3-dipoles in cycloaddition reactions or where the diazo group is incorporated into the final product. A review of the interesting background, structure and reactivity of aryne intermediates is also presented. In addition, some common syntheses of indazole compounds are presented as well as a brief discussion on the importance of indazole compounds as therapeutic agents. The second chapter discusses the synthetic routes employed towards the synthesis of the range of indazoles. Initially, the syntheses of the diazo carbonyl and aryne precursors are described. Next, the synthetic methods to prepare the indazole compounds are provided followed by discussion on derivatisation of the indazole compounds including N-deacylation, N-benzylation and ester side-chain transformation of some alkene-containing indazoles. A series of novel indazole derivatives were submitted for anti-cancer screening at the U.S National Cancer Institute (NCI). A number of these derivatives were identified as hit compounds, with excellent growth inhibition. The results obtained from biological evaluation from the NCI are provided with further results pending from the Community for Open Antimicrobial Drug Discovery. The third chapter details the full experimental procedures, including spectroscopic and analytical data for all the compounds prepared during this research.