Cervicovaginal cytology in patients undergoing pelvic radiotherapy using the Focalpoint system: results from the RODEO study

BackgroundEvaluate the performance of the Focalpoint system in identifying and classifying cervical cytology alterations from samples collected from patients treated with Radiotherapy (RT).MethodsThe reproducibility of manual and automated screening by cytotechnologists using the BD Focalpoint GS Imaging System was examined. Samples were collected from May 2010 to August 2011.ResultsA total of 378 treated with RT and 8,967 cytology samples from patients without previous RT, were evaluated. The kappa values for cytological diagnoses read manually and automated in cases without previous RT were as follows: < ASC-H vs. ¿ ASC-H¿=¿0.71; < LSIL vs. ¿ LSIL¿=¿0.66; and¿<¿HSIL vs. ¿ HSIL¿=¿0.67. The kappa for cytological diagnoses in post-RT women have showed: < ASC-H vs. ¿ ASC-H¿=¿0.71; < LSIL vs. ¿ LSIL¿=¿0.65; < HSIL vs. ¿ HSIL¿=¿0.57.ConclusionsThere was no significant difference among the kappa values we found. Post-RT cytology showed small diagnostic agreement between manual and automated examination.The authors are indebted to BD Brazil, which partially supported the study by providing the SurePath (TM) collection kits and equipment. The study design, screening, statistical analyses, and manuscript writing were independently performed by the Center for the Researcher Support of the Barretos Cancer Hospital

NDRG1 protein overexpression in malignant thyroid neoplasms

OBJECTIVES: The aim of this study was to examine the expression of the N-myc downstream-regulated gene 1 protein in benign and malignant lesions of the thyroid gland by immunohistochemistry. INTRODUCTION: N-myc downstream-regulated gene 1 encodes a protein whose expression is induced by various stimuli, including cell differentiation, exposure to heavy metals, hypoxia, and DNA damage. Increased N-myc downstream-regulated gene 1 expression has been detected in various types of tumors, but the role of N-myc downstream-regulated gene 1 expression in thyroid lesions remains to be determined. METHODS: A tissue microarray paraffin block containing 265 tissue fragments corresponding to normal thyroid, nodular goiter, follicular adenoma, papillary thyroid carcinoma (classical pattern and follicular variant), follicular carcinoma, and metastases of papillary and follicular thyroid carcinomas were analyzed by immunohistochemistry using a polyclonal anti- N-myc downstream-regulated gene 1 antibody. RESULTS: The immunohistochemical expression of N-myc downstream-regulated gene 1 was higher in carcinomas compared to normal thyroid glands and nodular goiters, with higher expression in classical papillary thyroid carcinomas and metastases of thyroid carcinomas (P < 0.001). A combined analysis showed higher immunohistochemical expression of NDRG1 in malignant lesions (classical pattern and follicular variant of papillary thyroid carcinomas, follicular carcinomas, and metastases of thyroid carcinomas) compared to benign thyroid lesions (goiter and follicular adenomas) (P = 0.043). In thyroid carcinomas, N-myc downstream-regulated gene 1 expression was significantly correlated with a more advanced TNM stage (P = 0.007) and age, metastasis, tumor extent, and size (AMES) high-risk group (P = 0.012). CONCLUSIONS: Thyroid carcinomas showed increased immunohistochemical N-myc downstream-regulated gene 1 expression compared to normal and benign thyroid lesions and is correlated with more advanced tumor stages

Evaluation of prognostic factors in stage IIA breast tumors and their correlation with mortality risk

Breast tumors exhibit extensive molecular and clinical heterogeneity. One of the most utilized breast carcinoma classifications is based on its molecular aspects and subdivides breast cancer into five major groups based on the expression of certain genes. In this study, we evaluated which factors are important in determining a prognosis after 5 years of follow-up for patients with clinical stage IIA breast tumors. We took into consideration the different phenotypes (luminal A luminal B HER-2 overexpression, basal and triple-negative), various epithelial-mesenchymal (EMT) molecular markers and adhesion molecules (E-cadherin, P-cadherin, N-cadherin, vimentin, twist snail and slug) and NOS-2, in addition to clinical and demographic data, tumor characteristics and treatment types. METHODS: The study population consisted of 82 patients with breast cancer. We analyzed eight molecular markers by immunohistochemistry on tissue microarrays containing breast tumor specimens from patients with ten years of follow-up, and we classified each tumor according to its estrogen receptor, progesterone receptor and HER-2 expression. We then placed the tumor into one of the above categories. RESULTS: The presence of several clinical and demographic factors, various histopathologies, treatment forms and several immunohistochemical markers were not associated with a worse prognosis for group IIA patients. The factors that were associated with a mortality risk were the triple-negative (odds ratio (OR) = 11.8, 95% confident interval (CI) = 2.0-70.3, P = 0.007) and basal (OR =18.4, 95% CI = 1.8-184.7, P= 0.013) phenotypic patterns. CONCLUSIONS: The EMT markers and NOS-2 were not mortality risk factors. Basal and triple-negative phenotypic patterns were related to a higher mortality risk in patients with stage IIA tumors

The significance of augmentedhigh-grade squamous intraepithelial lesion detection on pap test examination: partial results from the RODEO study team

OBJECTIVE: This study sought to ascertain the significance of augmented high-grade squamous intraepithelial lesion (HSIL) detection by Pap test using both conventional smear and liquid-based cytology (LBC) in a high-risk population. STUDY DESIGN: We conducted a direct-to-vial study to compare the diagnostic performance of Pap smear versus LBC in a high-risk population of women referred for colposcopy at a gynecologic ambulatory clinic at the Barretos Cancer Hospital in Brazil during 2011. RESULTS: The detection of both low-grade squamous intraepithelial lesions (LSILs) and HSILs was significantly greater (p = 0.04 and p = 0.033, respectively) in the LBC arm [84 LSIL cases (5.7%) and 148 HSIL cases (10.1%)] than in the conventional smear arm [66 LSIL cases (4.1%) and 126 HSIL cases (7.9%)]; however, no differences were found for invasive squamous carcinoma or adenocarcinoma (p = 0.678). Of 3,071 women who were examined cytologically (1,604 conventional preparations and 1,467 LBC) and colposcopically, biopsies were available for 279 conventional preparations (17.6%) and 325 LBC preparations (22.2%). No significant differences were found between the methods with respect to diagnostic performance. CONCLUSION: LBC was significantly superior to conventional smears for the detection of LSILs and HSILs, but these results did not influence biopsy confirmation. Both methods showed similar performances with high positive predictive values but very low sensitivities.This study was partially supported by BD, which donated the SurePath vials and Papanicolaou staining reagents. The study design, statistical analyses, interpretation of the results and manuscript development were carried out by the team of the Barretos Cancer Hospital with no involvement from BD

Performance and Reproducibility of Gynecologic Cytology Interpretation Using the FocalPoint System

Objectives: To assess whether automated screening in the cytologic examination of Papanicolaou smear slides results in smaller margins of error than manual screening. Methods: We compared cytotechnologists’ performance and reproducibility of manual and automated screening of 10,165 consecutive cervical cytology slides examined at Barretos Cancer Hospital using the FocalPoint system. Results: In total, 83% of atypical squamous cells of undetermined significance and greater were classified as quintiles 1 and 2; no high-grade squamous intraepithelial lesions and greater were observed in quintile 5. No statistically significant differences were found between manual and automated screening, using cervical biopsy specimens as the gold standard. Conclusions: FocalPoint safely screened high-grade lesions, which can be valuable for high-workload routines

Self-collection for high-risk HPV detection in Brazilian women using the care HPV™ test

Cervical cancer is the second most common cancer among Brazilian women. High-risk human papillomavirus (hr-HPV) persistence is the primary cause of cervical neoplasia. Early detection of hr-HPV is important for identifying women at risk for developing cervical lesions. Approximately 85% of new cases of cervical cancer worldwide and 50% of the total cervical cancer deaths occurred in developing countries. Here, a new methodology to support a cervical cancer screening program was evaluated in women from various Brazilian regions. METHODS: Two thousand women aged 18-77years were enrolled in an opportunistic cervical cancer screening program and were randomized into self-vaginal or health professional-guided cervical sampling groups. The Qiagen careHPV™ test was performed on all samples. Pap tests were performed on all women using liquid-based cytology. RESULTS: Positive hr-HPV results were obtained in 12.3% (245/2000) of women; similar rates were observed in self- or health professional-collected samples. Eighty-nine percent (1719/2000) of cervical cytologies classified as normal were negative to hr-HPV. Among the cytological samples, 36.6% classified as ASC-US+ were positive to hr-HPV, 78.8% were LSIL and 75.0% were HSIL. CONCLUSIONS: Self-sampled and health professional-sampled vaginal/cervical specimens did not differ in their rates of detection of hr-HPV. Therefore, HPV DNA testing in self-sampled vaginal cells is an alternative to primary screening in low-resource settings.The authors thank the following: Cancer Prevention Department Team, Cleyton Zanardo de Oliveira and Allini Mafra of the Researcher Support Team and the Pathology Depai Intent of the Barretos Cancer Hospital. Rui Manuel Reis and Andre Lopes Carvalho from the Molecular Oncology Center; Jose Eduardo Levi from Sao Paulo University; Cintia B. Oliveira, Raphael Haikel junior and Edmundo Mauad from Barretos Cancer Hospital. Luisa Lina Villa was supported by a grant from CNPq and FAPESP (INCT-HPV). Study Supported by CNPq - Process no 573799/2008-3 and FAPESP no 2008/57889-1. They also thank all volunteer women who participated of this study

Acessibilidade do termo de consentimento na pesquisa clínica no Brasil

Resumo O termo de consentimento livre e esclarecido tem a função de informar o participante de pesquisas clínicas sobre a natureza da pesquisa e seus direitos, formalizando sua decisão de participar. Estudos indicam que esse documento é redigido de modo complexo, comprometendo a autonomia do participante. Para este trabalho, foram redigidos dois termos de consentimento da mesma pesquisa hipotética, com estilos de redação diferentes. Ambos os termos foram analisados pela ferramenta Coh-Metrix Port, que avalia métricas linguísticas e acessibilidade textual. A análise indicou que os textos são complexos e exigem alta escolaridade para serem entendidos. Esses achados reforçam a percepção de que, no Brasil, os termos de consentimento podem ter sua real função comprometida e apontam a importância de modificar sua forma de elaboração

Could alarmingly high rates of negative diagnoses in remote rural areas be minimized with liquid-based citology? preliminary results from the RODEO study team

Objective: It was the aim of this study to compare diagnostic performances of the BD SurePath (TM) liquid-based Papanicolaou test (LBC) and the conventional Papanicolaou test (CPT) in cervical samples of women from remote rural areas of Brazil. Study Design: Specimens were collected by mobile units provided by Barretos Cancer Hospital. This report evaluates the manual screening arm of the RODEO study. Of 12,048 women seen between May and December 2010, 6,001 were examined using LBC and 6,047 using CPT. Results: Comparative (LBC vs. CPT) outcomes were: all abnormal tests, 2.1 versus 1.0%; ASC-US (atypical squannous cells of unknown significance), 0.7 versus 0.1%; ASC-H (atypical squamous cells with possible high-grade squannous intraepithelial lesions) and AGC (atypical glandular cells), 0.4 versus 0.3%; LSIL (low-grade squannous intraepithelial lesions), 0.7 versus 0.3%; HSIL (high-grade squamous intraepithelial lesions), 0.4 versus 0.2%, and unsatisfactory, 0.03 versus 0.08%. The LBC arm detected significantly more lesions (ASC-US+) than CPT (p < 0.001); however, when we divided the diagnoses into two groups, ASC-H (negative/ASC-US/LSIL) and ASC-H+ (ASC-H/AGC/HSIL), the difference was not statistically important (p = 0.213). Conclusions: With inherent difficulties in patient recruitment and patient compliance with cancer screening, best test performance including human papillomavirus test capability are vitally necessary in Brazil's struggle to reduce cervical cancer

The usefulness of an Online Simplified Screening Questionnaire (SSQ) in identifying work-related cancers

To obtain a history of occupational exposure in the workplace, the questionnaire is one of the main sources of information. The aim of this study was to develop an online questionnaire using the REDCap data management platform based on the Work-Related Cancer Surveillance Guidelines, reported by the Brazilian National Cancer Institute. Several issues were taken into consideration for its routine application. It should be simple, easy, capable of being applied in a short time and used in the clinical setting of collecting information on the occupational history of the cancer patient. Consequently, this could enable the compulsory notification of work-related cancer. The questionnaire was developed based on questions about the use of and exposure to carcinogenic factors at work and due to smoking. An entirely electronic version of the cancer patient interview was performed using tablets. The online questionnaire was applied at the Barretos Cancer Hospital, Barretos, to newly diagnosed patients from July 2016 to 2018. A total of 1063 patients were included, and 550 indicated positively when asked “Do you work, or have you worked with this substance and/or in this function?/job?” Of these potentially notified patients, 38 subsequently had compulsorily reported work-related cancer. Another important result of this study was the creation and development of a website. In conclusion, we developed an online tool that could facilitate hospital routines, contributing to generating data for the compulsory notification of work-related cancer and triggering investigations and surveillance actions in Brazil.This research was funded by Barretos Cancer Hospital and the Public Ministry of Labor Campinas (Research, Prevention and Education of Occupational Cancer). Vazquez, F.L. is supported by the Public Ministry of Labor Campinas (Research, Prevention, and Education of Occupational Cancer) in Campinas, Brazil

Surgical site infection: An observer-blind, randomized trial comparing electrocautery and conventional scalpel

AbstractAimTo evaluate the incidence of surgical site infection (SSI) based on the type of scalpel used for incisions in the skin and in subcutaneous tissues.MethodsObserver-blind, randomized equivalence clinical trial with two arms (electrocautery versus conventional scalpel) which evaluated 133 women undergoing elective abdominal gynecologic oncology surgery. A simple randomization stratified by body mass index (BMI: 30 kg/m2) was carried out. Women were evaluated at 14 and 30 days following the operation. A multivariate analysis was performed in order to check whether the type of scalpel would be a risk factor for SSI.ResultsGroup arms were balanced for all variables, excepted for surgical time, which was significantly higher in the electrocautery group (mean: 161.1 versus 203.5 min, P = 0.029). The rates of SSI were 7.4% and 9.7%, respectively, for the conventional scalpel and electrocautery groups (P = 0.756). The exploratory multivariate model identified body mass index ≥30 kg/m2 (OR = 24.2, 95% CI: 2.8–212.1) and transverse surgical incision (OR = 8.1, 95% CI: 1.5–42.6) as independent risk factors for SSI. The type of scalpel used in surgery, when adjusted for these variables and the surgery time, was not a risk factor for SSI.ConclusionThis study showed that the SSI rates for conventional scalpel and electrocautery were not significantly different. These results were consistent with others reported in the literature and would not allow a surgeon to justify scalpel choice based on SSI.Trial number: NCT01410175 (Clinical Trials – NIH)