Asociación entre polimorfismos de Glutation s-transferasa y cáncer cérvico uterino / Association between polymorphisms of Glutathione s-transferase and cervical cancer

Introducción: entre los factores de riesgo que favorecen la aparición de las lesiones cérvico uterinas, se encuentran la infección por virus de papiloma humano, la promiscuidad, el uso de anticonceptivos orales y el hábito de fumar. No obstante, varias investigaciones refieren que los polimorfismos genéticos podrían contribuir al desarrollo y progresión del cáncer cérvico uterino. Objetivo: identificar en la bibliografía revisada, la frecuencia de asociación de los polimorfismos de Glutation s - transferasa con el cáncer cérvico uterino y con factores de riesgo que inciden en la patología. Métodos: se realizó una extensa revisión de la literatura especializada a través de los buscadores en base de datos de PubMed, EBSCO, NCBI y BVS. Resultados: se constató la variabilidad en los reportes de las frecuencias alélicas de los genotipos GSTM1 y T1 en distintas poblaciones. Se corroboró en varios estudios revisados el hallazgo de asociación entre los genotipos GSTM1 y T1 nulos y cáncer cérvico uterino y, de igual forma con el consumo de tabaco y anticonceptivos orales por tiempo prolongado. Conclusiones: la bibliografía sobre el tema pone en evidencia que los genes que codifican la enzima Glutation s - transferasa intervienen en la protección celular contra los efectos citotóxicos, de manera que cuando éstos presentan alteración se afecta la actividad enzimática, lo que predispone a una mayor susceptibilidad al cáncer(AU)

Introduction: Among risk factors that lead to uterine cervix lesions we can find the human papilloma virus infection, promiscuity, use of oral contraceptive and smoking habit. However, several researches refer that genetic polymorphism could be related to the development and progression of the uterine cervix cancer. Objective: Identify the association of glutathione S- transferases polymorphism with uterine cervix cancer and risk factors relate with this disease, in the revise bibliography. Method: An extensive review was made of the specialized literature using web search in database PubMed, EBSCO, NCBI and BVS. Result: The variability of the allelic frequency of the GSTM1 and T1 genotypes in different populations was confirmed. Besides the association between null GSTM1 and T1 with uterine cervix cancer was corroborated. In addition, this association with smoking habit and the use of oral contraceptive for long time was corroborated. Conclusions: Consulted bibliography shows that genes encoding glutahione S- transferases enzyme contribute to the cellular protection against cytotoxic effects, therefore, alterations in these genes affect the enzymatic activity lead to a major susceptibility to suffer cancer(AU)

Tendências e projeções da mortalidade pelos cânceres específicos ao gênero no Brasil / Trends and projections of mortality for specific cancers gender in Brazil

Os cânceres que acometem os órgãos genitais masculinos e femininos, em conjunto com o câncer de mama, são responsáveis por cerca de 20% dos óbitos por câncer no mundo. Conhecer os padrões de mortalidade por esses cânceres no Brasil, as mudanças que se produziram ao longo do tempo, os grupos mais vulneráveis e a carga de mortalidade que se apresentará no futuro são elementos básicos para a estruturação das ações assistenciais e de vigilância do câncer. O objetivo desse estudo foi analisar as tendências de mortalidade pelos cânceres que acometem órgãos que são específicos a cada gênero e projetar a mortalidade por esses cânceres até o ano de 2030, para o Brasil, regiões e estados da federação. Trata-se de um estudo ecológico de base populacional que analisou os óbitos, ocorridos no período 1996 a 2010, decorrentes dos cânceres de colo do útero, corpo do útero, mama feminina, ovários, vulva, vagina, próstata, pênis e testículos, registrados no Sistema de Informação sobre Mortalidade; as informações sobre população foram obtidas do Instituto Brasileiro de Geografia e Estatística. Foi aplicada a Regressão loglineal (Joinpoint regression) com taxas padronizadas (população mundial: ASR-W) para estimar o Annual Percentage Change (APC), o Average Annual Percentage Change (AAPC), o intervalo de confiança 95% e os pontos de inflexão da curva; as projeções foram calculadas através do programa Nordpred, inscrito no programa R, utilizando o modelo idade-período-coorte, analisando posteriormente se as mudanças que se produzirão no futuro serão decorrentes da exposição aos fatores de risco e/ou da estrutura da população exposta ao risco. Todas as análises também foram aplicadas para o conjunto de todos os óbitos por câncer (com exceção dos cânceres de pele não-melanoma).

Para o Brasil, a mortalidade pelos cânceres de pênis (APC=1,5% IC95% 0,7;2,3 p<0,05), testículos (APC=1,6% IC95% 0,5;2,8 p<0,05) e ovários (APC=0,8% IC95% 0,1; 1,5 p<0,05), mostraram tendência de aumento, enquanto os cânceres de vulva e vagina (APC=-0,1% IC95% -0,9; 0,7 p=0,8), corpo de útero (APC= -0,3 IC95% -1,0; 0,5 p=0,4), mama (APC=0,4% IC95% -0,2;1,0 p=0,2) e de próstata (AAPC= 1,1% IC95% -0,2; 2,4 p=0,1) apresentaram tendência de estabilidade. A mortalidade por câncer de colo de útero apresentou tendência de redução (APC=-1,7% IC95%-2,2; -1,1 p<0,05). A análise do agrupamento de todos os óbitos por câncer observou tendência de aumento na mortalidade para o sexo masculino até o ano de 2006 (APC= 1,2% IC95% 0,6;1,8 p<0,01), seguido de um período de estabilidade. Para o sexo feminino, a tendência é de estabilidade (APC=0,4% IC95% -0,2;-1,8 p=0,2). As taxas de mortalidade para todos os cânceres analisados mostraram, de maneira geral, tendência de redução nas regiões sul e sudeste, tendência de aumento nas regiões norte e nordeste, e estabilidade para a região centro oeste. Na projeção da mortalidade para o ano 2030, as regiões norte e nordeste responderão pelas maiores taxas de mortalidade para os cânceres analisados; todavia, para as demais regiões, será observada redução nas taxas em comparação com o último período observado. Destacase o câncer de testículo, para o qual será observado aumento de 33% na carga da mortalidade até o ano 2030. Para os demais cânceres, não serão observadas variações consideráveis nas taxas de mortalidade para o Brasil entre o último período observado e o último período projetado. A estrutura e o tamanho da população brasileira serão os fatores que explicarão os padrões de mortalidade por esses cânceres no futuro, embora para a região nordeste, as variações serão explicadas, em maior medida, pelo aumento do risco para esses cânceres.

Conclui-se, portanto, que existe uma marcante desigualdade na distribuição da mortalidade pelos cânceres específicos ao gênero no Brasil, onde as regiões mais pobres apresentam um quadro de aumento significativo do número de óbitos ao longo de uma série histórica, e que em 2030, essas regiões responderão pelas maiores taxas de mortalidade no país, com ênfase para os cânceres de pênis, testículos e ovários. (AU)

Cancers that attack male and female genital organs, along with breast cancer, are responsible for approximately 20% of cancer-related deaths in the world. Knowledge on the mortality patterns for these cancers in Brazil, the changes produced throughout time, the most vulnerable groups and the mortality burden in the future are basic elements for structuring assistance and vigilance actions for cancer. The objective of this study was to analyze the mortality trends of cancers that attack gender-specific organs, and project mortality until the year 2030, for Brazil, its geographic regions, and federation states. A population-based ecological study is presented herein, which analyzed deaths occurring within the period 1996-2010, due to cancers of the uterine cervix, uterine corpus, female breast, ovary, vulva, vagina, prostrate, penis and testicles, registered in the Mortality Information System. Data on population was obtained from the Brazilian Institute of Geography and Statistics. Joinpoint regression was applied with standardized rates (world population: ASR-W) to estimate the Annual Percentage Change (APC), the Average Annual Percentage Change (AAPC), the confidence interval 95% and the inflection points of the curve. The projections were calculated by the Norpred program, inscribed within the R program, utilizing the age-period-cohort model, with posterior analysis of whether the changes produced in the future will be consequences of exposition to risk factors and/or structure of the population exposed to risk. The analyses were also applied to the set of all cancer-related deaths (with exception for non-melanoma skin cancers). For Brazil, mortality due to cancers of penis (APC=1.5% CI95% 0.7;2.3 p<0.05), testicles (APC=1.6% CI95% 0.5;2.8 p<0.05) and ovary (APC=0.8% CI95% 0.1; 1.5 p<0.05) showed increasing trends, while cancers of vulva and vagina (APC=-0.1% IC95% -0.9; 0.7 p=0.8), uterine corpus (APC=-0.3 CI95% - 1.0; 0.5 p=0.4), breast (APC=0.4% CI95% -0.2;1.0 p=0.2) and prostrate (AAPC= 1.1% CI95% -0.2; 2.4 p=0.1) presented stable trends. Mortality due to cervical cancer presented reducing trends (APC=-1.7% ICI95%-2.2; -1.1 p<0.05). Analysis of the grouping of all cancer-related deaths presented increasing mortality trends for the male gender until the year 2006 (APC= 1.2% CI95% 0.6; 1.8 p<0.01), followed by a stability period. For females, the trend was stable (APC=0.4% CI95% -0.2;-1.8 p=0.2). The mortality rates for all analyzed cancers revealed, generally, reducing trends for the South and Southeast regions, increasing trends for the North and Northeast regions, and stability for the Midwest region. Mortality projections for the year 2030 indicate that the North and Northeast regions will suffer the highest mortality rates for the analyzed cancers; however, for the remaining regions, reduced rates will be observed in comparison with the last period analyzed. It must be highlighted that, for testicle cancer, there will be an increase of 33% in mortality burden until the year 2030. For the remaining cancers, significant variations will not be observed in mortality rates for the last observed period and the last projected period in Brazil. The structure and size of the Brazilian population are the factors explaining the mortality patterns for these cancers in the future, although for the Northeast region, the variations will be explained mostly by the increase in risk for these cancers. It is concluded that there is a pronounced inequality in the distribution of gender-specific cancer mortality in Brazil, where the poorer regions present a significant increasing situation of the number of deaths throughout a historical series. In 2030, these regions will present the highest mortality rates in the country, with emphasis on penis, testicle and ovarian cancers. (AU)

Conocimientos, actitudes y prácticas sobre virus de papiloma humano (VPH) y cáncer de cuello uterino en mujeres de 30 y más años de edad, de un barrio ribereño de Asunción, (Bañado Sur). 2012 / Knowledge, attitudes and practice on human papilloma virus (HPV) and cervix cancer in women who were 30 years old or more, from a riverside neighborhood of Asuncion, (Bañado Sur). 2012

Introducción: El cáncer de cuello uterino es un problema de salud pública en Paraguay. Objetivo: Determinar conocimientos, actitudes y prácticas sobre virus del papiloma humano (VPH) y cáncer de cuello uterino en mujeres de 12 Unidades de Salud Familiar (USF) de Bañado Sur-Asunción, periodo abril-octubre 2012. Metodología: Estudio descriptivo de corte transversal, utilizando cuestionario estructurado autoadministrado. Resultados: La edad promedio de las encuestadas fue 42 años, la mayoría en unión libre o casadas (70%); 65% tienen educación básica y media, 56% son amas de casa. El 83% tienen seguro médico; 78% escuchó hablar sobre cáncer de cuello uterino, 74% de éstas en los centros de salud. El 10% de las encuestadas conoce el VPH y lo relaciona con la enfermedad, 90 % escuchó hablar sobre la prueba de Papanicolaou, el 27 % de ellas sabe en qué consiste; 90% de las mujeres demostró actitud favorable y 56% prácticas favorables respecto a la prevención de la enfermedad. Conclusiones: El estudio permite conocer la percepción que tiene una población de mujeres de un barrio marginal de la capital del país, respecto al cáncer de cuello uterino y el principal factor de riesgo que lo produce, a fin de incrementar la prestación de servicios de prevención de este tipo de cáncer, además de propiciar el trabajo interinstitucional e intersectorial en la prevención y control de la enfermedad en el país.

Introduction: Cervix cancer is a public health problem in Paraguay. Objective: To determine knowledge, attitudes and practices on human papilloma virus (HPV) and uterine cervix cancer in women from 12 Family Health Units (FHU) of the Bañado Sur- Asunción, April-October 2,012 period. Methodology: Descriptive cross-sectional study that used self-administered structured questionnaires. Results: The mean age was 42 years, most of them cohabitated or were married (70%); 65% had elementary and secondary education and 56% was housewife; 83% had medical insurance and 78% heard about uterine cervix cancer, 74% of them in health posts. Only 10% knew HPV and related it to a disease, 90% heard about Papanicolaou test, but only 27% knew what is, 90% showed favorable attitude and 56% favorable practices in relation to the disease prevention. Conclusions: The study provided information on the perception that a population of women from a marginal zone of the capital have in relation to cervical cancer and its main risk factor. This will allow increasing the supply of prevention services for this type of cancer, along with promoting inter-institutional and inter-sectorial work on the prevention and control of this disease in the country.

Value of diffusion weighted magnetic resonance imaging in the monitoring of neoadjuvant chemotherapy efficacy for uterine cervical cancer / 实用肿瘤学杂志

Objective To analyze the value of diffusion weighted imaging ( DWI) in assessing the effect of neoadjuvant chemotherapy of uterine cervix cancer .Methods Thirty one patients with LACC confirmed by pa-thology received conventional magnetic resonance imaging and DWI before and after neoadjuvant chemotherapy . The variation of DWI image and ADC was evaluated before and after chemotherapy .Results The correlation be-tween maximum diameter of the tumor before treatment (37.10 ±11.23) and pretreatment ADC value (0.83 ± 0.12)was not statistically significant(correlation coefficient r=-0.1746,P=0.3475);the correlation between the maximum diameter of the tumor(24.03 ±5.65)and ADC value(1.10 ±0.16)after treatment was not statisti-cally significant(correlation coefficient r=-0.2077,P=0 2621.);the degree of tumor size before and after the treatment was correlated with the degree of ADC increase (P0.05).Conclusion DWI sequence may be useful for early prediction and evaluation of curative effect to neoadjuvant chemotherapy for uterine cervical cancer .

Preservación de la fertilidad en estadios iniciales de cáncer de cuello uterino

La incidencia de cáncer cervical ha aumentado en mujeres jóvenes, en quienes se requiere prestar atención a la preservación de la fertilidad. Se presenta dos casos de pacientes con cáncer temprano de cuello uterino, en estadios iniciales IA2 e IB1 sin metástasis en ganglios pélvicos, y se analiza nuestra experiencia en la aplicación de la técnica quirúrgica de traquelectomía radical abdominal, de manera de preservar la fertilidad.

The incidence of cervical cancer has increased in young women in whom it is important to preserve fertility. Two cases of patients with early cervical cancer stages IA2 e IB1 and no pelvic lymph nodes metastasis are presented, and experience with abdominal radical trachelectomy in order to preserve fertility is analized.

The safety of conization in the management of adenocarcinoma in situ of the uterine cervix / 부인종양

OBJECTIVE: To evaluate the occurrence of residual or recurrent disease after conization for adenocarcinoma in situ (AIS) of the uterine cervix. METHODS: Medical records of 99 patients with a histologically diagnosis of AIS of the uterine cervix by conization between 1991 and 2008 were reviewed retrospectively. RESULTS: Seventy eight of 99 patients (78.8%) had negative and 18 (18.2%) had positive resection margins of the conization specimen, and 3 (3.0%) had unknown margin status. Of the 78 patients with negative margins, 45 underwent subsequent hysterectomy and residual AIS were present in 4.4% (2/45) of patients. Ten of the 18 patients with positive margins received subsequent hysterectomy and 3 patients (30%) had residual AIS. Twenty-eight patients had conservative treatment and during the median follow-up time of 23.5 months (range, 7 to 124 months), only one patient (3.6%) had recurrent AIS and was treated with a simple hysterectomy. Eight patients became pregnant after conization, 4 of them delivered healthy babies, one had a spontaneous abortion and 3 were ongoing pregnancies. CONCLUSION: Patients with positive resection margins after conization for AIS of the uterine cervix are significantly more likely to have residual disease. However, negative resection margin carries a lower risk for residual AIS, therefore conservative management with careful surveillance seems to be feasible in women who wish to preserve their fertility.

Ressonância magnética para avaliação dos limites dos campos clássicos de radioterapia em pacientes portadoras de neoplasia maligna de colo uterino / Magnetic resonance imaging in the evaluation of standard radiotherapy field borders in patients with uterine cervix cancer

OBJETIVO: Avaliar os limites de campo padronizados para radioterapia de neoplasia maligna de colo uterino com o uso de ressonância magnética e verificar a importância deste exame na redução de possíveis erros de planejamento com técnica convencional. MATERIAIS E MÉTODOS: Foram analisados, retrospectivamente, exames de ressonância magnética do planejamento de 51 pacientes tratadas devido a neoplasia de colo uterino. Os parâmetros estudados foram limites anterior e posterior no corte sagital. RESULTADOS: Observou-se, no corte sagital das ressonâncias magnéticas, que o limite de campo anterior apresentou-se inadequado em 20 (39,2 por cento) pacientes e que houve perda geográfica em 37,3 por cento dos casos no limite posterior. A inadequação de ambos os limites de campo não se relacionou com parâmetros clínicos como idade das pacientes, estadiamento, tipo e grau histológico. CONCLUSÃO: A avaliação dos limites de campo padronizados pela literatura com o uso de ressonância magnética mostrou altos índices de inadequação dos limites do campo lateral, assim como a importância do uso deste exame no planejamento radioterápico de pacientes portadoras de câncer de colo uterino com a finalidade de reduzir a perda geográfica no volume alvo de tratamento.

OBJECTIVE: To evaluate, by means of magnetic resonance imaging, the standardized field borders in radiotherapy for malignant neoplasm of uterine cervix, and to determine the role of this method in the reduction of possible planning errors related to the conventional technique. MATERIALS AND METHODS: Magnetic resonance imaging studies for planning of treatment of 51 patients with uterine cervix cancer were retrospectively analyzed. The parameters assessed were the anterior and posterior field borders on sagittal section. RESULTS: The anterior field border was inappropriate in 20 (39.2 percent) patients and geographic miss was observed in 37.3 percent of cases in the posterior border. The inappropriateness of both field borders did not correlate with clinical parameters such as patients' age, tumor staging, histological type and degree. CONCLUSION: The evaluation of standardized field borders with the use of magnetic resonance imaging has demonstrated high indices of inappropriateness of the lateral field borders, as well as the relevant role of magnetic resonance imaging in the radiotherapy planning for patients with uterine cervix cancer with a view to reduce the occurrence of geographic miss of the target volume.

Comparação dos resultados de exames preventivos e de rastreamento de câncer de colo do útero em mulheres brasileiras / Comparative study of the results found in preventive examinations and in uterine cervix cancer screening procedures performed with Brazilian women

Foram avaliados os resultados dos exames preventivos e realizado o rastreamento de câncer de colo de útero, registrados em uma clínica ginecológica de atendimento particular e conveniado, comparando-os com os dados do Sistema Único de Saúde (SUS). Os exames preventivos de colo de útero realizados, no período de janeiro de 2005 a julho de 2008, em clínica ginecológica de atendimento particular e conveniado de Florianópolis – SC foram analisadas, por meio de preenchimento de cadastro. Esses dados foram comparados com os resultados dos exames preventivos realizados pelo SUS na cidade de Florianópolis no mesmo período, disponíveis no site do DATASUS. A maioria dos exames realizados na clínica particular e conveniado ao SUS de Florianópolis apresentou resultados dentro da normalidade. Contudo, as amostras registradas no SUS demonstraram menor freqüência de alterações escamosas atípicas de significado indeterminado, possivelmente não neoplásico, neoplasia intra-epitelial cervicalgrau I, II e III, papilomavírus humano (HPV) e Candida spp, quando comparados com os dados obtidos em clínica de atendimento particular. Os exames citopatológicos realizados pela clínica particular registraram resultados de menor gravidade do que as análises realizadas pelo SUS. A variação nas características observadas pode ter ocorrido em função das diferenças sócio-econômicas e da periodicidade do exame.

This study assesses the results from preventives examinations and cervical cancer screenings carried out, betweenJanuary 2005 and July 2008, at a private gynecological clinic and at an agreed health service located in Florianópolis-SC, whose data were recorded in a reference file. These data were analyzed in parallel with those results from preventive exams performed by the Public Health System of Florianópolis in the same period, available at the DATASUS site. The majority of diagnosis results considered normal were found in patients examined at the private and at the agreed service clinic. Nonetheless, the samples analyzed by SUS (Brazilian public health system)showed a lower frequency of atypical squamous cells of unknown significance, such as cervical intraepithelial neoplasia 1, 2 and 3, Human papilomavirus (HPV) and Candida spp. than those reported by the private clinic. It was evidenced that the examinations carried out at the private and agreed gynecological clinic showed less severe cytopathogenic changes as compared to the results recorded by SUS examinations. This variation oncytopathogenicity findings might occurr due to socio-economic differences and periodicity of examinations.

Significance of detecting human papillomaviral DNA in cervical disease / 中国基层医药

Objective To study the detection and significance of human papillomaviral DNA(HPV-DNA) in cervical disease. Methods The express of HPV-DNA were detected by hybrid capture 2 in the patients with chronic cervicitis ( n = 166), cervical intraepithelial neolasia ( GIN ) ( n = 89 ) and uterine cervix cancer ( UCC ) ( n = 23 ). Results The positive expression rate of HPV-DNA in GIN Ⅰ , Ⅱ , Ⅲ grade and UCC were 70.8% (17/24) ,79. 3% (23/29) ,88.9% (32/36) ,91. 3% (21/23). They were significantly higher than those in chronic cervicitis 30.7% (51/166) (P ＜ 0. 01 );As the development of cervical disease, HPV-DNA positive expression had increasing trend.Conclusion The detection of HPV-DNA had an important role for the early UCC screening,prevention and treatment.

Avaliação da dose no reto em pacientes submetidas a braquiterapia de alta taxa de dose para o tratamento do câncer do colo uterino / Rectal dose assessment in patients submitted to high-dose-rate brachytherapy for uterine cervix cancer

OBJETIVO: O objetivo deste trabalho foi desenvolver um sistema dosimétrico termoluminescente capaz de avaliar as doses administradas ao reto de pacientes submetidas a braquiterapia de alta taxa de dose para o tratamento do câncer do colo uterino. MATERIAIS E MÉTODOS: O material termoluminescente utilizado para a avaliação da dose no reto foi o LiF:Mg,Ti,Na na forma de pó. O pó foi separado em pequenas porções de 34 mg, que foram acomodadas em um tubo capilar. Este tubo foi colocado em uma sonda retal, que era introduzida no reto da paciente. RESULTADOS: As doses administradas ao reto de seis pacientes submetidas a braquiterapia de alta taxa de dose para o tratamento do câncer do colo uterino foram avaliadas com dosímetros termoluminescentes e apresentaram boa concordância com os valores planejados, com base em duas radiografias ortogonais da paciente, imagens ântero-posterior e lateral. CONCLUSÃO: O sistema de dosimetria termoluminescente utilizado no presente trabalho é simples e de fácil utilização quando comparado a outros métodos de dosimetria do reto. Ele mostrou-se eficiente na avaliação da dose no reto de pacientes submetidas a braquiterapia de alta taxa de dose para o tratamento do câncer do colo uterino.

OBJECTIVE: The present study was aimed at developing a thermoluminescent dosimetric system capable of assessing the doses delivered to the rectum of patients submitted to high-dose-rate brachytherapy for uterine cervix cancer. MATERIALS AND METHODS: LiF:Mg,Ti,Na powder was the thermoluminescent material utilized for evaluating the rectal dose. The powder was divided into small portions (34 mg) which were accommodated in a capillary tube. This tube was placed into a rectal probe that was introduced into the patient's rectum. RESULTS: The doses delivered to the rectum of six patients submitted to high-dose-rate brachytherapy for uterine cervix cancer evaluated by means of thermoluminescent dosimeters presented a good agreement with the planned values based on two orthogonal (anteroposterior and lateral) radiographic images of the patients. CONCLUSION: The thermoluminescent dosimetric system developed in the present study is simple and easy to be utilized as compared to other rectal dosimetry methods. The system has shown to be effective in the evaluation of rectal doses in patients submitted to high-dose-rate brachytherapy for uterine cervix cancer.

Tumor volume measured by 3-D magnetic resonance imaging in the prediction of prognosis for cervical carcinoma / 대한산부인과학회지

OBJECTIVE: Clinical evaluation of tumor size in cervical cancer is often difficult. Digital imaging technique using computer has shown an eye opening progress. Quantitative analysis of tumor size or tumor volume using magnetic resonance imaging (MRI) has been reported as useful in the prediction of prognosis in patients with cervical cancer. The purpose of this study was to evaluate whether quantitative analysis can further improve the efficacy of using MR imaging to predict the prognosis of cervical cancer. METHODS: MRI on 0.5- or 1.5-T scanners was performed in 93 consecutive women with invasive carcinoma of the uterine cervix. Initial tumor diameter and volume were determined on T2-weighted images; volume was calculated by the standard technique of multiplying the sum of the areas by the slice thickness. Patients were treated by radical surgery, radiotherapy, or a concurrent chemoradiotherapy based on clinical International Federation of Gynecology and Obstetrics (FIGO) stage and individual patient criteria. Clinical data (patient age and FIGO stage), MRI-derived tumor dimensions (diameter and volume), and histological findings (tumor invasion depth and histological type) were associated and linked to patient outcome. RESULTS: Tumor volume on MRI was significantly associated with recurrence of cervical cancer (P=0.018). Univariate analysis demonstrated graphically that MRI-derived tumor volume and clinical stage were associated with progression-free survival. CONCLUSION: Our preliminary results suggest that tumor volume, determined by pretreatment MRI, predict progression-free survival for patients with invasive cervical carcinoma. This study reveals the value of MRI as an adjunctive tool to clinical evaluation of invasive cervical cancer.

Cobertura del programa de prevención de cáncer de cuello uterino en comunidades del Municipio Girardot, Estado Aragua / Coverage of Cervix Cancer Prevention Program in Communities of Girardot Municipality. Aragua state, Venezuela

El cáncer de cuello uterino es un problema de salud pública en países subdesarrollados, a pesar de contar con un método eficaz para la detección precoz como la citología, que sigue siendo la prueba más eficiente para el cribado de lesiones precursoras. Los países que han logrado disminuir la morbimortalidad, fundamentalmente ha sido por la cobertura del Programa de Prevención de la patología. En Venezuela y particularmente en el estado Aragua se reactiva el programa desde 1995, aumentando paulatinamente su cobertura para el año 2000 hasta 58,7%; sin embargo, el Municipio Girardot alcanza 37,7%; esto motivó a realizar un estudio en 10 comunidades para determinar los factores que puedan estar incidiendo en este nivel de cobertura. Se ejecutó un estudio de corte transversal a través de puestos centinelas; para ello se diseño una encuesta a los fines de recabar información sobre: toma de citologías, intervalos entre las muestras y centros de salud donde se realizan las mismas. Dicha encuesta se aplicó en 887 hogares a 689 mujeres con edades comprendidas, entre 25 y 64 años. Los resultados reportaron que 95,2% se practicaron el estudio alguna vez, de estas 90% se lo habían hecho en los últimos tres años. La cobertura de citología encontrada fue de 85,7%, de las cuales 48,1% fueron realizadas en establecimientos públicos; las mujeres con bajo nivel socioeconómico son las que mayormente se realizaron el estudio en los últimos tres años. La cobertura de citología en el grupo estudiado es mayor que la reportada por el sistema de salud para el mismo año.

Uterine cervix cancer is an important issue in Public Health of underdeveloped countries in spite of the avvailabity of cytology as an available method for its precocious detection and sifting of precursor lesions. In those countries where morbidity and mortality has declined, this has been achieved through the implementation of a preventive program. In Venezuela, and particularly in Aragua state, the program was reactivated in 1995 and coverage was increased as to achieve 58.7% by 2000. Meanwhile, in Girardot Municipality, the achievement was around 37.7%. This figure acted as motivating factor to performed a study in 10 communities as to assess the factors determining such variations. A cross sectional study was performed, and information was collected in sentinel, through a survey aimed to determine periodicity of cytology, and the Health Centers in which the samples were taken. The survey was applied in 887 houses with a sample of 689 women in ages between 25 and 64 years. Results demostrated that 95.2% have had at least one citology and 90% during the last there years. Assessed coverage was 85.7% of which 48.1% were performed in Public Health Services, mainly in women from the lower socio-economic strata. Cytology coverage in surveyed group is higher that the figures reported by the Health System during the same period.

Effect on radiation-induced apoptosis of HeLa cells by inhibiting expression of NF-?B / 中国癌症杂志

Background and purpose: NF-?B is activated by tumor necrosis factor,some chemotherapeutic agents,and ionizing radiation.The activation of NF-?B could result in inhibition of apoptosis.NF-?B,regulated by PDTC(pyrrolidine dithiocarbamate),is a specific inhibitor of NF-?B.The purpose of our study was to explore the impact of inhibiting expression of NF-?B on radiation-induced apoptosis of uterine cervix cancer HeLa cells.Methods:Inhibition of NF-?B in HeLa cells was performed by treatment with 100 ?mol/L PDTC for 2 hours.Cells were irradiated at 0,2,4 and 6 Gy with or without PDTC.The expression of NF-?B in nuclear was determined by western blot,and apoptosis was evaluated by using the TUNEL assay.Cell proliferation was evaluated by using MTT assay.Results:NF-?B activation was induced by radiation and inhibited by PDTC.Inhibition of radiation-induced NF-?B activation resulted in inhibiting cell proliferation(P

The Study of Morphological Distributions of Lymphatic Vessels in Peripheral Areas of Uterine Cervix Cancer and Metastasis / 医学研究杂志

Objective To investigate the metastasis mechanism by observing morphological distributions of lymphic vessels in peripheral areas of the different development of uterine cervix cancer. Methods Cancer tissues from the center, peripheral and normal areas of uterine cervix cancer respectively were collected. The paraffin sections and semithin sections which were stained with HE were applied to those tissues for exploring the configurations and distributions of lymphic vessels of the cancer under a microscope. And the ultrathin sections were applied to those tissues for exploring under a electronic microscope. Results Under the microscope, the basement membrane had been destroyed by cancer cell, which continued to infiltrate interstitial tissue. Lymphic vessels were increased and dilated in peripheral areas of uterine cervix cancer than those in normal areas. Moreover, the walls of lymphic vessels were hazy and broken. Conclusion The increase and morphologic changes of lymphic vessels in peripheral areas of uterine cervix cancer will play an important role in lymphatic metastasis.

Utilização da ressonância magnética para o planejamento radioterápico dos tumores de colo de útero / Magnetic resonance imaging in the radiation treatment planning of uterine cervix cancers

OBJETIVOS: Verificar o índice de erros geográficos no planejamento radioterápico convencional de pacientes com carcinoma de colo uterino por meio da ressonância magnética (RM); comparar os dados de estadiamento da FIGO pelos exames físico e de RM e avaliar o estudo do Raio-X contrastado de reto na previsão do erro geográfico. MATERIAIS E MÉTODOS: Oitenta pacientes com diagnóstico histológico de carcinoma espinocelular de colo uterino, com indicação de radioterapia, foram analisadas. Após o estadiamento clínico (FIGO), foi realizada ressonância magnética da pelve e estas imagens comparadas aos campos clássicos de radioterapia, técnica de 4 campos em tijolo. Considerou-se erro geográfico, quando o volume alvo não foi englobado pelos campos, com margens mínimas de 1cm. Os dados de exame físico e RM foram comparados. RESULTADOS: Entre as 80 pacientes analisadas, os limites clássicos dos campos não foram adequados em 45 (56%). Os limites críticos foram as bordas anterior (1/3 anterior da sínfise púbica) ou posterior (limite em S2-S3) dos campos laterais de irradiação. Evidenciou-se grande discrepância entre o exame físico e a RM no que se refere à análise de informações para o estadiamento. Na maioria das vezes, o exame físico sub-estadiou as lesões, principalmente na detecção de doença vaginal e parametrial. Lesões com diâmetro antero-posterior maior que 6cm e volume acima de 100cm3 apresentaram correlação estatisticamente significante com o erro geográfico. O posicionamento da parede anterior do reto fora do limite posterior dos campos laterais, no raio-X contrastado mostrou correlação estatisticamente significante com o erro geográfico. CONCLUSÕES: Em relação aos limites dos campos de irradiação a RM foi decisória para adequação dos campos de radioterapia, na maioria das pacientes. O estadiamento por RM, comparado ao exame físico, mostrou-se preciso na avaliação de volume tumoral e extensão da doença. No presente estudo, a avaliação do deslocamento...

OBJECTIVES The purposes of this study were to verify the chances of geographic miss in conventional 2-dimensional radiotherapy planning in patients with uterine cervix cancer, by means of magnetic resonance imaging (MRI); to compare the data from FIGO staging system with MRI findings; and to evaluate the influence of contrasted rectum X-ray in predicting geographic miss. MATERIAL AND METHODS: Eighty patients with uterine cervical carcinoma were analyzed. After clinical staging (FIGO), magnetic resonance imaging of the pelvis was performed. The images were compared to the classic 4-field technique (box) of radiotherapy. Geographic miss was considered when the tumor volume was not included in the irradiation fields with at least 1cm margins. Data of physical examination and RM were compared. RESULTS: In 45 (56,2%) of the 80 studied patients, fields? limits were not adequate. The anterior (anterior 1/3 of pubis) and posterior limits (S2-S3) of the lateral fields of irradiation were critical. Great discrepancy was observed when physical exam was compared to MRI findings. In most cases, physical exam tended to under-stage the tumors, mainly due to vaginal and parametrial extension. Tumors with antero-posterior diameter larger than 6cm and volume above 100cm3 presented statistically significant correlation with geographical miss. Displacement of the anterior rectal wall outside the posterior limit of the lateral fields in the contrasted X-ray was also significantly correlated with geographical miss. CONCLUSIONS: MRI findings detected and prevented geographic misses in the majority of the patients. When compared to physical examination, tumor volume and extension were better defined by MRI. In the present study, the evaluation of the anterior rectal wall displacement in the lateral x-ray of the irradiation fields was associated with the risk of geographical miss.

The usefulness of vascular endothelial growth factor as a prognostic factor in uterine cervix cancer / 대한산부인과학회지

OBJECTIVE: This study was designed to determine the relationship between the VEGF (Vascular Endothelial Growth Factor) expression and histopathologic prognostic factors and 5-year survival rate. METHODS: We examined the expression of the VEGF by immunohistochemical staining in 40 specimens collected from invasive uterine cervix cancer patients. We compared the results of relationship between the VEGF expression and several histopathologic prognostic factors by using Fisher exact test for statistical analysis. RESULTS: All specimens showed low or high immunoreactivity. There was no significant correlation between the expression of the VEGF and histopathologic prognostic factors (p>0.05) except for pathological cell types (p<0.05). Parametrial invasion, the stage and age showed statistically significant correlation with 5 year survival rate (p<0.05). There was no statistically significant correlation between the VEGF expression and 5 year survival rate. CONCLUSION: VEGF expression had no relation with prognostic factors except for histopathologic cell types. Its expression may not play an important role in the prognosis of the uterine cervix cancer patients.

Enhancement of Radiation Effects by Flavopiridol in Uterine Cervix Cancer Cells / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To determine the effects of combinations of radiation and flavopiridol, an inhibitor of cyclin-dependent kinases and global transcription, in a human uterine cervix cancer cell line. MATERIALS AND METHODS: Human uterine cervix cancer cells (HeLa), cultured to the mid-log phase, were exposed to X-rays, flavopiridol, and combinations of X-rays and flavopiridol in various sequences. The end point in this study was the clonogenic survival, which was measured via clonogenic assays. In order to determine the intrinsic cytotoxicity of flavopiridol, 0, 5, 12.5, 25, 37.5, 50 and 100 nM of flavopiridol were added to cell culture media. In the combination treatment, four different schedules of flavopiridol and irradiation combinations were tested: treatment of flavopiridol for 24 hours followed by irradiation, simultaneous administration of flavopiridol and irradiation, and irradiation followed by flavopiridol (for 24 hours) at intervals of 6 and 24 hours. The fraction of cells surviving after the combination treatment with 2 Gy of radiation (SF2) was compared with that of the fraction of cells surviving after treatment with irradiation alone. RESULTS: The cytotoxicity of flavopiridol was found to be dose-dependent, with an IC50 of 80 nM. No cytotoxic enhancements were observed when flavopiridol and radiation were administered simultaneously. Flavopiridol, administered either 24 hours before or 6 hours after irradiation, exerted no sensitizing effects on the cells. Only one protocol resulted in a radiosensitizing effect: the administration of flavopiridol 24 hours after irradiation. CONCLUSION: Flavopiridol enhanced the effects of radiation on a uterine cervix cancer cell line in vitro, and this enhancement was both sequence- and time-dependent.

Primary studies on the anti-uterine cervix cancer effects of the extract ZE4 from Lysmachia clethroides Duby / 中国药理学通报

Aim To estimate the anti-uterine cervix cancer effects of the extracts from Lysimachia clethroides Duby in vivo and in vitro. Methods Inhibitory effect on growth was observed by MTT, 3H-TdR and colony-forming units assay. Apoptosis was detected by Hoechst fluorescent staining analysis. The effect on cell migration and morphology was observed by scratch test; Detecting effects of ZE4 on transplant tumor (U14) in mice through observing the tumor weight and organ index. Results ZE4 could inhibit the growth and migration of HeLa cell significantly and induce cell apoptosis. Its half inhibitory concentration (IC50) at 48h was 40.56 mg?L-1 by 3H-TdR assay. The inhibition rate of ZE4 against U14 was 49.9% at the dose of 400 mg?kg-1. Conclusions ZE4 could inhibit the growth of uterine cervix cancer in vitro and in vivo.

Long Term Follow Up Results of Serum Squamous Cell Carcinoma Antigen Level in Uterine Cervix Cancer Treated by Radiotherapy / 대한방사선종양학회지

PURPOSE: To evaluate the long term significance of the squamous cell carcinoma (SCC) antigen (Ag) as a tumor marker in uterine cervix carcinoma. MATERIALS AND METHODS: The SCC antigen levels of pre-radiotherapy and serial post-radiotherapy serum were analyzed in 48 patients who received radiotherapy with histologically proven primary SCC of the uterine cervix. RESULTS: Pre-radiotherapy SCC Ag level was high (>or=2 ng/ml) at 79.2%. After the treatment, the SCC Ag level was significantly decreased. The SCC Ag level measured at about 3 months after radiotherapy was high at 23.0%. In further follow up measurements, a rise of the SCC Ag to a high level was well associated with clinical relapse. The specificity of the elevated SCC Ag level in association with recurrent or persistent disease was 100%, and the sensitivity was 85.7%. In 3 of 4 lung metastasis cases, lung lesions were detected in chest PA before elevation of the SCC Ag level. The median lead time of the high SCC Ag level to clinical recurrence was 4 months. CONCLUSION: SCC Ag was a good tumor marker for monitoring treatment effect in patients with increased pre-treatment levels except in case of early lung metastasis. Elevation of the SCC Ag level after radiotherapy accurately predicted the treatment failure with lead time of 4 months. But, in early lung metastasis cases, the SCC level may be normal temporarily. Thus, chest PA should be checked to evaluate the presence of lung metastasis.

Gene Expression Profiles in Cervical Cancer with Radiation Therapy Alone and Chemo-radiation Therapy / 대한방사선종양학회지

PURPOSE: To analyze the gene expression profiles of uterine cervical cancer, and its variation after radiation therapy, with or without concurrent chemotherapy, using a cDNA microarray. MATERIALS AND METHODS: Sixteen patients, 8 with squamous cell carcinomas of the uterine cervix, who were treated with radiation alone, and the other 8 treated with concurrent chemo-radiation, were included in the study. Before the starting of the treatment, tumor biopsies were carried out, and the second time biopsies were performed after a radiation dose of 16.2~27 Gy. Three normal cervix tissues were used as a control group. The microarray experiments were performed with 5 groups of the total RNAs extracted individually and then admixed as control, pre-radiation therapy alone, during-radiation therapy alone, pre-chemoradiation therapy, and during-chemoradiation therapy. The 33P-labeled cDNAs were synthesized from the total RNAs of each group, by reverse transcription, and then they were hybridized to the cDNA microarray membrane. The gene expression of each microarrays was captured by the intensity of each spot produced by the radioactive isotopes. The pixels per spot were counted with an Arrayguage(R), and were exported to Microsoft Excel(R). The data were normalized by the Z transformation, and the comparisons were performed on the Z-ratio values calculated. RESULTS: The expressions of 15 genes, including integrin linked kinase (ILK), CDC28 protein kinase 2, Spry 2, and ERK 3, were increased with the Z-ratio values of over 2.0 for the cervix cancer tissues compared to those for the normal controls. Those genes were involved in cell growth and proliferation, cell cycle control, or signal transduction. The expressions of the other 6 genes, including G protein coupled receptor kinase 6, were decreased with the Z-ratio values of below -2.0. After the radiation therapy, most of the genes, with a previously increase expressions, represented the decreased expression profiles, and the genes, with the Z-ratio values of over 2.0, were cyclic nucleotide gated channel and 3 Expressed sequence tags (EST). In the concurrent chemo-radiation group, the genes involved in cell growth and proliferation, cell cycle control, and signal transduction were shown to have increased expressions compared to the radiation therapy alone group. The expressions of genes involved in angiogenesis (angiopoietin-2), immune reactions (formyl peptide receptor-like 1), and DNA repair (cAMP phosphodiesterase) were increased, however, the expression of gene involved in apoptosis (death associated protein kinase) was decreased. CONCLUSION: The different kinds of genes involved in the development and progression of cervical cancer were identified with the cDNA microarray, and the proposed theory is that the proliferation signal starts with ILK, and is amplified with Spry 2 and MAPK signaling, and the cellular mitoses are increased with the increased expression of Cdc 2 and cell division kinases. After the radiation therapy, the expression profiles demonstrated the evidence of the decreased cancer cell proliferation. There was no significant difference in the morphological findings of cell death between the radiation therapy alone and the chemo-radiation groups in the second time biopsy specimen, however, the gene expression profiles were markedly different, and the mechanism at the molecular level needs further study.