Cervical digital photography for screening of uterine cervix cancer and its precursor lesions in developing countries.

PURPOSE: This study aims to evaluate and to compare the performance of cervical digital photography (CDP) to the visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI) methods for screening the uterine cervix cancer and its precursor lesions in developing countries. METHODS: A cross-sectional study was performed in Brazil. 176 women were evaluated by VIA, VILI, CDP with acetic acid and CDP with Lugol's iodine. Kappa statistic was used to estimate the interobserver and intermethod agreement. Sensitivity, specificity and diagnostic accuracy of the four methods (VIA, VILI, CDP with acetic acid, CDP with Lugol's iodine) was calculated. RESULTS: Interobserver agreement for CDP with acetic acid was K = 0.441 and for CDP with Lugol's iodine was K = 0.533; intermethod agreement of VIA and CDP with acetic acid, K = 0.559; and of VILI and CDP with Lugol's iodine, K = 0.507. Sensitivity and specificity of CDP with acetic acid were 84.00 and 95.83 %, and of CDP with Lugol's iodine were 88.00 and 97.26 %, respectively. The diagnostic accuracy of CDP with acetic acid and CDP with Lugol's iodine was 92.78 and 94.90 %, respectively. CONCLUSION: This was the first study to assess the CDP with Lugol's iodine performance, which had similar performance to the CDP with acetic acid. CDP is considered a promising method for screening the uterine cervix cancer and its precursor lesions in developing countries.

Minimal cold knife conization height for high-grade cervical squamous intraepithelial lesion treatment.

OBJECTIVES: To assess the relationship between cold-knife conization specimen height, cervical intraepithelial neoplasia (CIN II/III) size and endocervical margin involvement by CIN II/II. STUDY DESIGN: A cross-sectional study was performed. Cold knife cone specimens with a diagnosis of CIN II/III were selected. Epidemiological data and pathology reports were obtained through a chart review. All samples from each cone specimen showing CIN II/III and the squamocolumnar junction were selected. Cone height (mean ± standard deviation), intraepithelial lesion size, and size of endocervical surgical margins were measured. RESULTS: Four hundred and forty-seven samples were analyzed from 97 cone specimens. Section size ranged from 3.4 to 29.7 mm, tumor size from 0.3 to 17.5mm, and tumor distance from the endocervical margin, from 0.0 to 22.0mm. Age and parity were similar in the positive vs. negative margin groups (37.6 ± 10.0 years vs. 37.7 ± 11.9 years respectively, p=0.952, and 2.2 ± 1.7 births vs. 2.6 ± 1.9 births respectively, p=0.804), whereas cone height (22.4 ± 6.9 mm vs. 17.1 ± 5.6mm, p=0.013) and tumor size (6.12 ± 3.25 mm vs. 10.6 ± 4.45 mm, p<0.001) were significantly different in negative vs. positive margin groups respectively. CONCLUSIONS: Use of cone height to identify the likelihood of negative margins enables better estimation of the risk-benefit ratio of greater risks of bleeding, stenosis, and obstetric complications (cervical incompetence) versus greater risks of residual and recurrent disease.

Comparison of loop electrosurgical conization with one or two passes in high-grade cervical intraepithelial neoplasias.

The use of loop electrosurgical conization (LEC) for the treatment of large high-grade cervical intraepithelial neoplasias (CINs) is often associated with a difficult procedure that results in accidental sample fragmentation, thermal damage and sometimes the presence of positive margins. This study aims to compare LEC that removes the cervical cone in two blocks (anterior and posterior cervical lips - LEC2) with LEC performed with one pass of the loop (LEC1). In a randomized, controlled trial, patients that needed conization due to high-grade CIN were assigned to one of the techniques. There were no differences in terms of age, cone histopathological diagnosis, blood loss, vaginal injuries, stenosis of the cervical os and specimen artifacts. LEC2 required less hemostatic sutures. LEC2 showed no specimen fragmentation, while LEC1 did (0 vs. 5.9%; p = 0.10). As expected, LEC2 samples were heavier (p = 0.01), included a larger ectocervical area (p = 0.001) and, therefore, had a greater volume (p < 0.001) compared to LEC1 samples. The height of the LEC2 specimens was smaller than that of LEC1 specimens (p < 0.001). LEC2 yielded fewer cases of positive margins (12.7%) than LEC1 (33.3%; p = 0.021). We conclude that the LEC2 technique is an effective treatment choice: it is safe for the patient, with better outcomes regarding sample quality than LEC1. Further studies are encouraged regarding this procedure.

P53 and BCL-2 as prognostic markers in endometrial carcinoma.

The objective of this study was to verify the frequency of p53 and BCL-2 immunohistochemical expression in patients with endometrial carcinoma and to correlate it with histological factors (histological type, tumor grade, depth of myometrial invasion, lymph node involvement and surgical staging) and survival. Forty-eight patients with endometrial carcinoma who were submitted to primary surgical treatment were assessed. p53 and BCL-2 immunohistochemical expression was determined using paraffin blocks containing the tumor area. p53 and BCL-2 expression was detected in 39.6% and 58.3% of the tumors, respectively. No significant difference was found regarding the frequency of p53 expression when analyzing histological type (33.3% in endometrioid tumors, 58.3% in non-endometrioid tumors; p = 0.176), depth of myometrial invasion (p = 0.632) and surgical staging (I-11.1%, II-66.7%, III-57.1%; p = 0.061). p53 expression was significantly more frequent in undifferentiated tumors (p = 0.007) and in those showing lymph node involvement (p = 0.030). Univariate analysis showed a positive association with death (RR, 3.358; CI, 1.386-8.134; p = 0.005) and short-term survival. The present study did not reveal any correlation between BCL-2 expression and histopathologic markers or survival. In conclusion, this study showed that p53 expression is directly correlated with undifferentiated tumors, lymph-node involvement and risk of death. On the other hand, BCL-2 expression was not correlated with any known histological factors.

Value of the International Federation for Cervical Pathology and Colposcopy (IFCPC) Terminology in predicting cervical disease.

OBJECTIVE: To evaluate the colposcopic accuracy according to the International Federation for Cervical Pathology and Colposcopy (IFCPC) 2002 terminology. MATERIALS AND METHODS: A series of 3,040 women derived from a general population were screened by means of Pap smear, unaided visual inspection, and high-risk human papillomavirus testing. All colposcopic examination results with abnormal findings and with biopsy confirmation (n = 468) were recorded, reviewed by 2 blinded colposcopists according to the IFCPC nomenclature, and included in this analysis. RESULTS: The IFCPC terminology was easily reproduced by the 2 observers with excellent interobserver agreement (kappa =.843). Colposcopy had a sensitivity of 86% and a specificity of 30.3% in distinguishing healthy cervix from that with cervical intraepithelial neoplasia (CIN)/carcinoma. In distinguishing healthy cervix/low-grade lesions (CIN 1) from that with high-grade lesions (CIN 2/3)/carcinoma, colposcopy had a sensitivity of 61.1% and a specificity of 94.4%. Colposcopic findings graded as major changes had the highest positive predictive value for detecting high-grade lesion/carcinoma. The colposcopic abnormalities within the transformation zone and large lesions were more closely related to high-grade lesion/carcinoma, whereas a sharp outer border, multiple colposcopic abnormalities, and iodine negativity were not statistically related to severe lesions. CONCLUSIONS: Colposcopy using the new IFCPC classification is a potentially effective screening method; when used for diagnosis, a histological sampling is necessary. The categorization of major changes and minor changes is appropriate. It is important to describe the lesion localization in relation to the transformation zone and the lesion size because these characteristics are related to high-grade lesions.

Teratoma imaturo de ovário na gestação: relato de caso e revisão da literatura / Immature ovarian teratoma in pregnancy: case report and literature review

O teratoma imaturo de ovário é uma neoplasia maligna derivada de células embrionárias de diferenciação somática. Sua incidência é baixa, e rara em gestantes. Costuma se manifestar em pacientes jovens, sendo, frequentemente, assintomáticos. Relata-se aqui o caso de uma paciente de 21 anos que veio à consulta apresentando ecografia obstétrica de 25 semanas, com presença de massa anexial à esquerda. Uma nova ecografia, realizada dois dias após a primeira avaliação, revelou massa de aspecto heterogêneo, sólido-cístico, septada, com 9,4cm em seu maior diâmetro. Havia presença de líquido livre na cavidade abdominal, ocupada por formações teciduais de distribuição ampla. Duas semanas após a primeira consulta, foi submetida à laparotomia exploradora com salpingo-ooforectomia unilateral e ressecção de implantes peritoneais, obtendo citorredução ótima. O laudo histopatológico revelou teratoma imaturo de ovário grau III, com líquido de ascite negativo para células malignas. Realizados 3 ciclos de quimioterapia adjuvante, segundo protocolo BEP (bleomicina, etoposide e cisplatina), os dois primeiros com a gestação em curso. Com 36 semanas de gestação, iniciou-se a indução de trabalho de parto, com boa evolução. O recém-nascido apresentou um índice de Apgar de 8/8, sem sinais de danos secundários à quimioterapia. No momento, a paciente encontra-se assintomática e livre de doença no décimo quarto mês pós-operatório. Acredita-se que esse trabalho possa acrescentar ao conhecimento atual da doença, visto a raridade do caso e a escassa quantidade de literatura disponível.

Biologia molecular do câncer cervical / Molecular biology of cervical cancer

A carcinogênese é um processo de múltiplas etapas. Alterações no equilíbrio citogenético ocorrem na transformação do epitélio normal a câncer cervical. Numerosos estudos apoiam a hipótese de que a infecção por HPV está associada com o desenvolvimento de alterações malignas e pré-malignas do trato genital inferior. Neste trabalho são apresentadas as bases para a compreensão da oncogênese cervical. O ciclo celular é controlado por proto-oncogenes e genes supressores. Quando ocorrem mutações, proto-oncogenes tornam-se oncogenes, que são carcinogênicos e causam multiplicação celular excessiva. A perda da ação de genes supressores funcionais pode levar a célula ao crescimento inadequado. O ciclo celular também pode ser alterado pela ação de vírus, entre eles o HPV (Human Papiloma Virus), de especial interesse na oncogênese cervical. Os tipos de HPV 16 e 18 são os de maior interesse, freqüentemente associados a câncer cervical e anal. O conhecimento das bases moleculares que estão envolvidas na oncogênese cervical tem sido possível devido a utilização de técnicas avançadas de biologia molecular. A associação destas técnicas aos métodos diagnósticos clássicos, poderão levar a uma melhor avaliação das neoplasias cervicais e auxiliar no desenvolvimento de novas terapias, talvez menos invasivas e mais efetivas.

Carcinogenesis involves several steps. Disorders of the cytogenetic balance occur during the evolution from normal epithelium to cervical cancer. Several studies support the hypothesis that the Human Papiloma Virus (HPV) infection is associated to development of premalignant and malignant lesions of cervical cancer. In this review we show the basis to understand cervical oncogenesis. The cell cycle is controlled by protooncogenes and supressive genes. This orchestrated cell cycle can be affected by virus such as HPV. Of special interest in the cervical carcinogenesis are the HPV subtypes 16 and 18. How HPV immortalizes cervical cells is not fully understood. Advances have been made in the application of molecular biology techniques in the understanding of this mechanism. Once established, these techniques will lead to a better assessment of cervical neoplasias and help the development of new therapies, hopefully less invasive and more effective.

Uso clínico do teste para HPV nas lesões epiteliais da cérvice uterina / Clinical applications of HPV - testing in the epithelial lesions of the uterine cervix

Atualmente, considera-se que a infecção pelo papiloma virus humano é uma condição necessária para que maioria das lesões pré-invasoras e invasoras ocorra no colo uterino. Várias técnicas para identificação do DNA-HPV têm permitido desvendar a patogênese desta infecção e suas repercussões clínicas. No entanto, apesar do papel importante das novas técnicas, em geral seu emprego clínico ainda é controvertido. Para o emprego correto destes exames diagnósticos é necessário compreender melhor o significado dos resultados positivos

Vaginal Müllerian papilloma in a 2-year-old child.

Papillomas of the lower genital tract are rare benign lesions, which cause vaginal bleeding in girls. We report a case in a 2-year-old girl. Few cases have been described in children and adolescents. However, it should be considered as a possible diagnosis in girls with sanguineous vaginal discharge.

Phase II trial of cisplatin plus decitabine, a new DNA hypomethylating agent, in patients with advanced squamous cell carcinoma of the cervix.

On the basis of the demonstrated single-agent activity of cisplatin in patients with advanced cervical cancer and the observation of in vitro synergism between this agent and decitabine, a new DNA hypomethylating agent, we designed a phase II trial in which the combined use of the two agents are used as first-line therapy in patients with recurrent and/or metastatic disease. Eligible patients were those with histopathologically proven diagnosis of squamous cell carcinoma of the cervix, which was not considered suitable for curative surgery and/or irradiation, having measurable disease, leukocyte counts more than or equal to 4,000/microl, thrombocyte counts more than or equal to 100,000/microl, serum creatinine more than or equal to 1.5 mg/dl, and normal liver function tests. Initial dose of cisplatin was 40 mg/m(2), whereas decitabine was 50 mg/m(2) for 3 consecutive days every 21 days. Because of toxicity, the dose of cisplatin was reduced to 30 mg/m(2). Twenty-five patients were included in the study; 24 of them were eligible for the evaluation of toxicity, whereas 21 of them were eligible for the evaluation of tumor responses. Nineteen (79.2%) patients had received prior radiotherapy. A total of 75 cycles of chemotherapy were administered to the patients, with a median of 3 cycles (range: 1-8) per patient. The most frequently observed side effect was neutropenia, which was National Cancer Institute- Common Toxicity Criteria grades III and IV in 68.0% of cases. One patient died of complications caused by drug-related neutropenic sepsis. The most common nonhematologic grades III and IV toxicities were nausea and vomiting, which occurred in 17.3% and 9.3% of the cycles, respectively. Of a total of 21 patients evaluable for tumor response, 8 (38.1%) achieved a partial response, whereas stable disease was documented in 5 cases (23.8%). Median progression-free interval (PFI) was 16 weeks, and median survival was 19 weeks (95% CI 7.9-31.2). Objective responses were more frequent in patients with metastatic lesions in nonirradiated sites. Cisplatin- decitabine combination was moderately active in patients with advanced squamous cell carcinoma of the cervix, mainly in patients presenting with metastatic disease at previously nonirradiated sites. However, this regimen produced significant hematologic toxicity. Further studies with this combination including a larger patient population, preferably with the concomitant administration of hematopoietic growth factors, are warranted.

Diagnostico, patologia, tratamento e evolucao de tumores ovarianos em criancas e adolescentes / Diagnosis, pathology, treatment and evolution of ovarian tumor in children and adolescents

Os tumores de ovario representam 1,2 a 1,5 por cento das doencas malignas , na infancia e ate 20 por cento deles, ocorrem antes da menarca. Neste trabalho e apresentada a experiencia do setor de oncologia genital feminina do Hospital das Clinicas de Porto Alegre, no tratamento...

Bases biomoleculares da oncogênese cervical / Molecular basis of cervical oncogenesis

A incidência e a mortalidade de câncer cervical têm diminuído, em parte pelo diagnóstico precoce e tratamento de lesões precursoras do câncer cervical. Neste trabalho são apresentadas as bases para a compreensão da oncogênese cervical. Diversos estudos demonstraram que o maior risco para desenvolver câncer de colo uterino é a não realização de exames citopatológicos, rotineiramente. O ciclo celular é controlado por genes supressores e estimuladores da proliferação celular. Quando ocorrem mutações, proto-oncogenes tornam-se oncogenes, que são carcinogênicos e causam multiplicação celular excessiva. Os genes supressores, em contraste, contribuem para o desenvolvimento de câncer quando são inativados por mutações. A perda da ação de genes supressores funcionais pode levar a célula ao crescimento inadequado. O ciclo celular também pode ser alterado pela ação de vírus, entre eles o HPV (human papilloma virus), de especial interesse na oncogênese cervical. Os tipos HPV 16 e 18 são os de maior interesse, freqüentemente associados a câncer cervical e anal. O mecanismo pelo qual os tipos de HPV transformam as células ainda não é completamente compreendido. O conhecimento das bases moleculares que estão envolvidas na oncogênese cervical tem sido possível devido a utilização de técnicas avançadas de biologia molecular. Algumas destas técnicas permitem identificar grupos de HPV de alto ou baixo risco (captura híbrida) ou identificação de tipos virais específicos (PCR). São técnicas de fácil utilização em laboratórios equipados, embora ainda com custo elevado.