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Luiz Carlos Zeferino

Publications and source records attributed to Luiz Carlos Zeferino.

17 recordsLinked to original sources

Whole, Turret and step methods of rapid rescreening: is there any difference in performance?

We compared the performance of the Whole, Turret and Step techniques of 100% rapid rescreening (RR) in detection of false-negatives in cervical cytology. We tested RR performance with cytologists trained and among those without training. We revised 1,000 consecutive slides from women participating in an ongoing international screening trial. Two teams of experienced cytologists performed the RR techniques: one trained in RR procedures and the other not trained. The sensitivities in the trained group were Whole 46.6%, Turret 47.4% and Step 50.9%; and in the non-trained group were 38.6, 31.6 and 47.4%, respectively. The kappa coefficient showed a weak agreement between the two groups of cytologists and between the three RR techniques. The RR techniques are more valuable if used by trained cytologists. In the trained group, we did not observe significant differences between the RR techniques used, whereas in the non-trained group, the Step technique had the best sensitivity.

False Negative Reactions↗

Protein expression of c-erbB-2 and p53 in normal ducts, ductal carcinoma in situ and invasive carcinoma of the same breast.

CONTEXT AND OBJECTIVE: Breast cancer is thought to derive from progressively aberrant, non-invasive breast lesions, but it is not known exactly how invasive breast cancer develops from these lesions. The aim of this study was to verify the changes in c-erbB-2 and p53 protein expression between non-neoplastic ducts, ductal carcinoma in situ and invasive ductal carcinoma found in the same breast. DESIGN AND SETTING: This was a cross-sectional study at Centro de Atenção Integral à Saúde da Mulher, Campinas, Brazil. METHODS: Fifty-six women with invasive ductal carcinoma and ductal carcinoma in situ in the same breast were included. The expression of c-erbB-2 and p53 proteins was assessed in non-neoplastic and neoplastic cells using immunohistochemical techniques. RESULTS: The c-erbB-2 protein was absent in non-neoplastic ducts but was present in 46% and 36% of in situ and invasive carcinoma components, respectively. Only 2% of non-neoplastic ducts, and 18% and 16% of ductal carcinoma in situ and invasive carcinoma components, respectively, were positive for p53 protein. No significant difference in c-erbB-2 and p53 protein expression was observed between in situ and invasive components. The nuclear grade agreement between in situ and invasive carcinoma was very good. CONCLUSIONS: The invasiveness of ductal carcinoma in situ seems to be independent of the Her-2/neu and TP53 genes. The general features of an occurrence of breast carcinoma are formulated at the outset of carcinogenesis, and the Her-2/neu and TP53 genes are involved.

Breast↗

Cervical cancer in the developing world.

In developed countries, systematic screening programmes have reduced the morbidity and mortality resulting from cervical cancer. Cytological methods of screening have been the mainstay in these countries. Nevertheless, there is scant evidence that cytology-based screening has had any effect in reducing cervical cancer mortality in less-developed countries. In fact, the challenge in less-developed countries is surpassed by the complex array of problems that go far beyond the introduction of simplified technologies. Currently, there are two main issues on this subject: the assessment of simpler screening methods, and the evaluation of different strategies regarding which women to target and the screening interval. Achieving high rates of coverage and compliance of the target population through high-quality procedures has remained the most difficult goal to achieve. Nevertheless, it is believed that creativity, flexibility and well-focused use of resources can reduce the inequitable burden of cervical cancer borne by women in poor countries.

Adult↗

Variants of human papillomavirus types 16 and 18: histological findings in women referred for atypical glandular cells or adenocarcinoma in situ in cervical smear.

Human papillomavirus (HPV) genotypes cannot fully explain the histological diagnosis of women with glandular abnormalities detected by cervical smear. Thus, this study was designed to analyze the distribution of HPV-16 and HPV-18 variants in women referred because of atypical glandular cells and adenocarcinoma in situ in their cervical smears and its association with histological results. Twenty-four women with HPV-16 and 6 with HPV-18, selected from 160 women with cervical smears suggestive of glandular abnormalities, were included. Histological results showed cervicitis (1 case), squamous neoplasia (18 cases), glandular neoplasia (7 cases), and glandular neoplasia associated with a squamous component (4 cases). Among the 24 cases presenting HPV-16, the European variant was detected in 15 (62%) and the Asian American in 9 (38%). Among the 15 cases associated with the European variant, 14 (93%) presented squamous neoplasia and 1 (7%) invasive adenocarcinoma. Asian-American HPV-16 variants were significantly associated with histological diagnosis of glandular neoplasia alone (odds ratio, 9.3 [1.4-60.2]) or associated with squamous neoplasia (odds ratio, 18.7 [1.5-232.3]). Adenocarcinomas were detected in 4 of 6 HPV-18-positive cases, being 2 cases had the European variant, 1 had the Asian Amerindian variant, and 1 had the African variant. The association of HPV-16 with squamous or glandular neoplasia is explained by its variants. In this study, squamous neoplasia was related to the European variant of HPV-16, whereas glandular neoplasia was related to the Asian-American variant. Glandular neoplasia is associated with HPV-18, but the results of our analysis of its variants were inconclusive.

Adenocarcinoma↗

Organization of cervical cancer screening in Campinas and surrounding region, São Paulo State, Brazil.

Cervical cancer screening remains a challenge in developing countries due to a complex array of problems. This paper aimed to describe the experience with organization of cervical cancer screening in three districts of Campinas and the surrounding region in São Paulo State, Brazil, and to report the resulting data. The program was organized in a pyramid format, and the health care hierarchy was defined according to the complexity and total number of medical procedures. Screening has been extended currently to 88 municipalities, of which 51 are equipped with colposcopy and eight have facilities for treating advanced cervical cancer. The standardized incidence rate for cervical cancer in Campinas was 14.2/100,000 women per year in 1993-1995, and the standardized mortality rate per district ranged from 2.7 to 3.0 per 100,000 women in 1997-1998. This project has clearly shown that hierarchical and decentralized organization of health procedures is a necessary condition for achieving the goals of an effective cervical cancer screening program.

Brazil↗

DNA repair gene polymorphisms and susceptibility to familial breast cancer in a group of patients from Campinas, Brazil.

Several studies have reported that the genes involved in DNA repair and in the maintenance of genome integrity play a crucial role in protecting against mutations that lead to cancer. Epidemiologic evidence has shown that the inheritance of genetic variants at one or more loci results in a reduced DNA repair capacity and in an increased risk of cancer. Polymorphisms have been identified in several DNA repair genes, such as XRCC1, XPD, XRCC3, and RAD51, but the influence of specific genetic variants on repair phenotype and cancer risk has not yet been clarified. This was a case-control study design with three case groups: 53 women with breast cancer and family history; 33 women with sporadic breast cancer; 175 women with no breast cancer but with family history. The control group included 120 women with no breast cancer and no family history. The PCR-RFLP method was used to analyze the XRCC1-Arg399Gln, XPD-Lys751Gln, XRCC3-Thr241Met, and RAD51-G135C polymorphisms. No statistically significant differences were found between the case groups and the control group for any of the polymorphisms analyzed, and also between the breast cancer and family history group and the sporadic breast cancer group. Sample sizes of women with breast cancer, whether familial or sporadic, were insufficient to show any small true differences between the groups, but we have to consider that currently there is no clear consensus with respect to the association of these polymorphisms with breast cancer risk. Considering the data available, it can be conjectured that if there is any risk association between these single-nucleotide polymorphisms and breast cancer, this risk will probably be minimal. The greater the risk associated with cancer, the smaller the sample size required to demonstrate this association, and the data of different studies are usually, therefore, more concordant.

Adult↗

p63, cytokeratin 5, and P-cadherin: three molecular markers to distinguish basal phenotype in breast carcinomas.

Human breast carcinomas represent a heterogeneous group of tumors diverse in behavior, outcome, and response to therapy. However, the current system of pathological classification does not take into account biologic determinants of prognosis. The purpose of this study was to classify and characterize breast carcinomas based on variations in protein expression patterns derived from immunohistochemical analyses on tissue microarrays (TMAs). Therefore, 11 TMAs representing 168 invasive breast carcinomas were constructed. Breast tumors were classified into four different subtypes depending on estrogen receptor (ER) and HER2 expression. Basal-type tumors expressed neither of these proteins and represented 7.6% of our series; basal-like HER2-overexpressing tumors did not express ER and represented 17.7%; luminal-type tumors expressed ER and represented 72.8% of this series (luminal A 56.3%, luminal B 16.5%). Moreover, we characterized each subtype based on P-cadherin (P-CD), p63, cytokeratin (CK)5, BCL2, and Ki67 expression. Basal-type tumors were mostly grade III, more frequently P-CD-, p63-, and CK5-positive, and had a high proliferation rate. Conversely, luminal-type tumors rarely expressed basal markers and had a low grade and proliferation rate. Basal-like HER2-overexpressing tumors showed a basal-type profile similar with a high grade and up-regulation of P-CD and CK5. With this study, we show that P-CD, p63, and CK5 are important molecular markers that can be used to distinguish a basal phenotype. In addition, we also demonstrate the usefulness of TMAs in breast carcinoma immunoprofiling.

Biomarkers, Tumor↗

Analysis of BRCA1 and BRCA2 mutations in Brazilian breast cancer patients with positive family history.

CONTEXT AND OBJECTIVE: BRCA1 and BRCA2 are the two principal hereditary breast cancer susceptibility genes, and the prevalence of their mutations among Brazilian women is unknown. The objective was to detect BRCA1 and BRCA2 mutations in Brazilian patients with breast cancer, so as to establish genetic profiles. DESIGN AND SETTING: Cross-sectional study, in Centro de Atenção Integral à Saúde da Mulher, Universidade Estadual de Campinas, Brazil, and Institute of Pathology and Molecular Immunology, University of Porto, Portugal. METHODS: Thirty-one breast cancer patients with positive family history (criteria from the Breast Cancer Linkage Consortium) were studied, and genomic DNA was extracted from peripheral blood. Single-strand conformation polymorphism was used for the analysis of exons 2, 3, 5, and 20 of BRCA1. Cases showing PCR products with abnormal bands were sequenced. Exon 11 of BRCA1 and exons 10 and 11 of BRCA2 were directly sequenced in both directions. RESULTS: Four mutations were detected: one in BRCA1 and three in BRCA2. The BRCA1 mutation is a frameshift located at codon 1756 of exon 20: 5382 ins C. Two BRCA2 mutations were nonsense mutations located at exon 11: S2219X and the other was an unclassified variant located at exon 11: C1 290Y. CONCLUSION: The BRCA1 or BRCA2 mutation prevalence found among women with breast cancer and such family history was 13% (4/31). Larger studies are needed to establish the significance of BRCA mutations among Brazilian women and the prevalence of specific mutations.

Adult↗

[Pap smear, hybrid capture II, and visual inspection in screening for uterine cervical lesions].

The objective of this study was to evaluate alterations in Pap smear, hybrid capture II (HCII), and visual inspection with acetic acid (VIA) in 684 women treated at a primary health care unit. The performance and agreement of the exams were evaluated. The study also described social, demographic, and reproductive factors and their association with uterine cervical lesions. Women had specimens taken for Pap smear, HCII, and VIA. When at least one of the tests was positive, colposcopy was performed and targeted biopsies were taken from any suspicious lesions. Performance of tests was evaluated. Women's distribution in relation to social, demographic, and reproductive factors and histological diagnosis was evaluated using the odds ratio. Among 198 women with at least one positive screening test, only 21 showed histological disease. Sensitivities of the tests were similar. VIA and Pap smear presented higher specificity than HCII. Only absence of a previous Pap smear was associated with the presence of histological disease. Pap smear performed better than VIA and HC II. Absence of previous cytology was associated with histological disease.

Acetic Acid↗

DNA recovery from Hybrid Capture II samples stored in specimen transport medium with denaturing reagent, for the detection of human papillomavirus by PCR.

The purpose of this study was to examine the quality of DNA recovered for human papillomavirus (HPV) detection using polymerase chain reaction (PCR) in samples that had been collected for Hybrid Capture II (HCII), testing and stored in specimen transport medium (STM) with denaturing reagent at -20 degrees C for 18 months. Endocervical tissue was collected from 92 women for HCII assay using the Digene STM, and a Papanicolaou smear was carried out in all cases. Seven women had normal colposcopy results. The remaining 85 patients underwent colposcopy-directed biopsy or cervical conization for histological investigation. Of the 92 samples tested, 84 were HCII-positive and 8 were negative. Quality control for amplification was carried out with beta-globin primers G73 and G74, and HPV was tested using PGMY09 and PGMY11. DNA was recovered from 83 of the 92 samples (90%). Among the 84 samples HCII-positive initially, HPV was detected by PCR in 56 (67%). PCR did not detect HPV DNA in the eight samples that were HCII-negative, although five of them were positive for beta-globin. This paper describes a novel DNA extraction technique that may permit exact HPV typing in stored samples collected originally for HCII testing, making it possible to carry out retrospective investigations to retrieve information on specific HPV types in large HCII series.

Cervix Uteri↗

[Sentinel node study with patent blue in cervical cancer].

OBJECTIVE: The purpose of this study was to determine the feasibility of sentinel node identification in patients with invasive cervix cancer undergoing radical hysterectomy and pelvic lymphadenectomy using intraoperative lymphatic mapping with patent blue dye. METHODS: Fifty one patients wtih Figo I and II cervical cancer were submitted to radical hysterectomy and pelvic lymphadenectomy. The patent blue V was injected around the tumor before beginning surgery. At the time of pelvic lymphadenectomy, lymph nodes with obvious uptake of the dye were separated from the remainder of the lymphadenectomy specimen. RESULTS: Sentinel nodes were detected in 32 of the 51 patients. Four cases of false negative were observed. The specificity, sensitivity, positive predictive value and negative predictive value were 38.6%, 42.8%, 10% and 80.9%, respectively. CONCLUSIONS: Identification of sentinel node with patent blue dye is feasible in cervical cancer. A larger series will be required to establish sentinel detection in cervical cancer for further therapy concepts and planning.

Adult↗

Detection of high-risk human papillomavirus (HPV) DNA by Hybrid Capture II in women referred due to atypical glandular cells in the primary screening.

We assessed the detection of high-risk human papillomavirus DNA (HPV-DNA) in women examined by a second Pap smear due to atypical glandular cells (AGC) detected in their screening Pap smear. In 91 women included in the study, a second Pap smear was taken and HPV-DNA test was performed using Hybrid Capture II (HC II). The second Pap smear showed no abnormalities in 28 (31%) cases, ACG in 17 (19%) cases, and high-grade squamous intraepithelial lesions (HSIL) or worse in 24 (26%). HC II test was positive in 36% of the cases. Considering the second Pap smear diagnosis, HPV-DNA was detected in 87% of the women with HSIL, 100% of women with in situ adenocarcinoma, and only in 11% of the women with no abnormalities. The use of the second Pap smear combined with HPV-DNA may improve the management of women with AGC in the primary screening.

DNA Probes, HPV↗

Quantification of angiogenesis in cervical cancer: a comparison among three endothelial cell markers.

OBJECTIVES: The aim of this study was to evaluate the quantification of angiogenesis by assessing microvessel density in cervical cancer, comparing the performance of three monoclonal antibodies: anti-CD34 and BNH9, which are still little known markers in cervical neoplasia, and anti-CD31. METHODS: Fifty-four consecutive patients diagnosed with stages I and II invasive cervical cancer undergoing radical hysterectomy and bilateral pelvic lymphadenectomy were evaluated. The monoclonal primary antibodies used were anti-CD34, anti-CD31 and BNH9 antibody. The areas of highest microvessel density were used for counting microvessels in 10 high-power fields. Microvessel density was the mean vessel number counted in 10 high-power fields. RESULTS: The mean of microvessel density was 10.3, 9.7 and 5.8 for anti-CD34, BNH9 and anti-CD31, respectively. According to the Kruskal-Wallis nonparametric test, microvessel density estimated by anti-CD34 and BNH9 was significantly higher than the microvessel density estimated by anti-CD31. The difference between microvessel density measured by anti-CD34 and BNH9 was not statistically significant. There was diagnostic agreement in 44 out of 54 cases for anti-CD34 and BNH9 monoclonal antibodies, kappa coefficient being 0.63. The kappa coefficient was 0.41 between anti-CD34 and anti-CD31 and 0.26 between anti-CD31 and BNH9. CONCLUSIONS: The anti-CD34 and BNH9 seem to have higher sensitivity than anti-CD31. The agreement to quantify microvessel density between anti-CD34 and BNH9 is higher than between them and anti-CD31. Additionally, considering that the BNH9 is much less unknown than anti-CD34 and that they showed very similar performance, the BNH9 clinical significance should be test in different neoplasms.

Adult↗

Human papillomavirus DNA detection and histological findings in women referred for atypical glandular cells or adenocarcinoma in situ in their Pap smears.

OBJECTIVE: To evaluate the association between high-risk human papillomavirus (HPV) DNA detection and histological diagnosis in women referred for atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) at Pap smear. METHODS: In this cross-sectional study, 146 women referred for AGC (124), AGC with high-grade squamous intraepithelial lesion (HSIL) (15), or AIS (7) were tested for HPV DNA using Hybrid Capture II (HC II). All women underwent colposcopic examination, and cervical biopsy was performed for 95 patients. Fifty-one women referred due to AGC with normal colposcopy and normal second Pap smear were scheduled for control visits every 4 months. RESULTS: The overall prevalence of HPV DNA was 38%. HPV DNA was detected in 93% of the women with HSIL associated with AGC and in 71% of women with AIS Pap smear, being significantly higher when compared with the prevalence (29%) in women with AGC alone. Forty-five women (30.8%) had clinically significant histological lesions (CIN 2 or worse). High-risk HPV DNA was detected in only 16% of the women without significant abnormalities in biopsy, in contrast to 96% of those who had CIN 2 or CIN 3 and 75% of women with AIS. Eighty-five percent of women with invasive cervical carcinoma (squamous or adenocarcinoma) tested positive for HPV DNA. HPV DNA detection was significantly associated with histological diagnosis of CIN 2 or worse, with an odds ratio (OR) = 51.8 (95% CI 14.3-199.9). CONCLUSION: HPV DNA detection was strongly associated with the severity of cervical lesion (CIN 2 or worse) in women referred for AGC or AIS in their Pap smear. These data implicate the use of HPV testing in triage of women with AGC Pap smears.

Biopsy↗

Quality assurance in cervical smears: 100% rapid rescreening vs. 10% random rescreening.

OBJECTIVE: To compare 100% rapid rescreening of cervical smears with 10% random rescreening as a method of quality assurance. STUDY DESIGN: A total of 5215 smears, randomly selected from smears reported as negative by cytotechnologists during routine screening, underwent 100% rapid rescreening by senior cytotechnologists. Ten percent of these smears, selected at random, were rescreened by other senior cytotechnologists. The gold standard was defined by cytopathologists, who rescreened all 5215 smears. After excluding unsatisfactory smears detected by cytopathologists, 4271 were included in the analysis. RESULTS: The 100% rapid rescreening method identified 69.9%, 95.7% and 100%, respectively, of atypical squamous cells of undetermined significance, low grade squamous intraepithelial lesion and high grade squamous intraepithelial lesion cases reported by the cytopathologists. The 100% rapid rescreening method showed a sensitivity of 73.5% and specificity of 98.6%. The 10% rescreening method showed sensitivity of 40.9% and specificity of 98.8%. CONCLUSION: One hundred percent rapid rescreening is an efficient method of internal quality assurance in cervical smear diagnosis. It can reduce the false negative rate and therefore can provide greater certainty to women who have received negative results. Well-trained cytotechnologists are able to identify abnormal smears in 1-minute rapid rescreening.

Female↗

[Postoperative adverse effects in gynaecological and breast surgeries].

OBJECTIVES: To analyze the occurrence of adverse effects in the first 24-hour postoperative/postanesthetic period in women undergoing minor gynecologic or minor breast surgeries and to identify main associated factors. METHODS: A cross-sectional study was conducted with 159 women who underwent minor gynecologic or breast surgeries. The women were admitted to the hospital one day before surgery and remained hospitalized for at least 24 hours after surgery. The anesthetic techniques performed were intercostal nerve blockade, spinal anesthesia, and general anesthesia. RESULTS: The most frequent adverse effects were vomiting, nausea and pain that occurred in 40.3% of women. Of these effects, 60% were observed in the first four hours and 80% were observed in up to six hours after surgical intervention. Women submitted to intercostal blockade received earlier postanesthetic release. Spinal anesthesia was most frequently associated with postoperative pain, although with a lower incidence of nausea and vomiting when compared to general anesthesia and intercostal blockade. The incidence of pain was higher in women who smoked. CONCLUSIONS: A six-hour period of postoperative observation appeared to be adequate for assessment of most complications and adverse effects occurring in women who undergo minor gynecologic or minor breast surgeries.

Adolescent↗