Eduardo Batista Cândido

Exploring cervical cancer mortality in Brazil: an ecological study on socioeconomic and healthcare factors

To evaluate the correlation between socioeconomic and healthcare factors and cervical cancer mortality rates, as well as the accessibility to prevention and treatment across Brazilian states and macroregions. The aim is to highlight the multifaceted challenge of addressing cervical cancer mortality, particularly in low-and middle-income countries. This ecological study analyzed public data from the Brazilian National Institute of Cancer (INCA), the National Institute of Geography and Statistics (IBGE), and the Brazilian Ministry of Health. Data were collected on indicators such as the Human Development Index (HDI), physician density, average household income, human papillomavirus (HPV) vaccine coverage, Pap smear screening rates, radiotherapy machine density, and non-White population rates by state and macroregion across Brazil. Spearman's rank correlation test and simple linear regression analysis were employed. Cervical cancer mortality rates are statistically lower in women with health insurance, positive self-perception of health, located in states with a higher HDI, higher per capita household income, greater density of physicians, and higher availability of radiotherapy machines. In contrast, mortality rates proportionally increase according to poverty levels, as expected, and rates of non-White population. Considering public health, HDI scores significantly affected Pap smear test coverage, the number of radiotherapy machines, and HPV vaccine uptake. The North and the Southeast regions have, respectively, the lowest and the highest socioeconomic indicators, proportional to their mortality rates. No significant correlation was found between mortality rates and HPV vaccine or Pap smear coverage. Cervical cancer mortality in Brazil is significantly influenced by socioeconomic and healthcare disparities. This study provides a data-driven basis for public health strategies that address both medical and social determinants of health.

Hormone therapy after risk-reducing surgery in patients with BRCA1/BRCA2 mutation: evaluation of potential benefits and safety

SUMMARY Women with mutations in the BRCA 1 and 2 genes are at increased risk for ovarian and breast cancer and therefore candidates for risk-reducing surgery, including salpingo-oophorectomy and mastectomy. Risk-reducing salpingo-oophorectomy (RRSO) is considered the most effective prophylactic measure for ovarian cancer prevention in this group of patients. This procedure involves loss of ovarian function and induced menopause. Estrogen therapy is the most effective treatment for controlling vasomotor symptoms and improving the quality of life of climacteric women. However, the potential hormonal stimulation of these tumors and the risk of breast cancer are a concern regarding the safety of hormone replacement therapy (HRT) in this population. This article aims to review the current evidence regarding the potential benefits and safety of HRT after RRSO.

High-Grade Transformation in Adenoid Cystic Carcinoma of the Bartholin Gland: Case Report

Abstract Introduction In the present study, we report a case of primary adenoid cystic carcinoma (ACC) of the Bartholin gland with high-grade transformation (HGT). Adenoid cystic carcinoma of the Bartholin gland is a rare tumor and HGT has only been reported in head and neck tumors. Case Report A 77-year-old woman with a non-ulcerated vulvar lesion on the topography of the right Bartholin gland. The patient was submitted to tumor resection followed by V–Y island flap and adjuvant radiotherapy. The histopathological examination revealed primary ACC of the Bartholin gland, with areas of HGT and extensive perineural invasion. The immunohistochemical study with p53 showed a diffuse and strong positive reaction in areas with HGT. After 24 months of follow-up, the patient presented distant metastases and died, despite having undergone to chemotherapy. Conclusion As far as we know, this case is the first description in the literature of HGT in ACC of the Bartholin gland, and HGT appears to be associated with tumor aggressiveness.

Association of insulin-like growth factor II mrna-binding protein 3 (IMP3) expression with prognostic and morphological factors in endometrial cancer

Endometrial cancer (EC) is a heterogeneous disease with recurrence rates ranging from 15 to 20%. The discrimination of cases with a worse prognosis aims, in part, to reduce the length of surgical staging in cases with a better prognosis. This study aimed to evaluate the association between Insulin-like growth factor II mRNA-binding protein 3 (IMP3) expression and prognostic and morphological factors in EC. This retrospective, cross-sectional, analytical study included 79 EC patients - 70 endometrioid carcinoma (EEC) and 9 serous carcinoma (SC) - and 74 benign endometrium controls. IMP3 expression was evaluated by immunohistochemistry-based TMA (Tissue Microarray), and the results were associated with morphological and prognostic factors, including claudins 3 and 4, estrogen and progesterone receptors, TP53, and KI67. IMP3 expression was significantly higher in SC compared to EEC in both extent (p<0.001) and intensity (p=0.044). It was also significantly associated with worse prognostic factors, including degree of differentiation (p=0.024, p<0.001), staging (p<0.001; p<0.001) and metastasis (p=0.002; p<0.001). IMP3 expression was also significant in extent (p=0.002) in endometrial tumors compared with controls. In addition, protein TP53 and KI67 showed significant associations in extent and intensity, respectively. IMP3 expression was associated with worse prognostic factors studied. These findings suggest that IMP3 may be a potential biomarker for EC poorer prognosis.

Efficacy of direct oral anticoagulants versus low-molecular-weight heparin for thromboprophylaxis after gynecological cancer surgery: A systematic review and meta-analysis

To evaluate the efficacy and safety of direct oral anticoagulants (DOACs) compared to enoxaparin, a low molecular weight heparin (LMWH). for postoperative thromboprophylaxis in patients undergoing gynecologic cancer surgery. This systematic review and meta-analysis followed Cochrane Handbook guidelines and PRISMA recommendations. We searched PubMed, Embase, Scopus, and CENTRAL for randomized controlled trials (RCTs) and observational studies comparing DOACs and LMWHs for postoperative VTE prophylaxis in gynecologic cancer surgeries. Outcomes included VTE incidence, major bleeding, clinically relevant non-major bleeding (CRNMB), hospital readmission, and drug adherence. The risk of bias was assessed using the Cochrane tools (RoB-2 and ROBINS-I), and statistical analyses were conducted using Review Manager 5. Five studies (1436 patients) were included: two RCTs and three observational studies. There was no significant difference in 30-day VTE incidence between DOAC and LMWH groups (OR, 0.55; 95 % CI, 0.17 to 1.77; P = 0.31). Similarly, major bleeding rates showed no difference (OR, 1.13; 95 % CI, 0.29 to 4.42; P = 0.90). DOACs significantly reduced CRNMB events compared to LMWHs (OR, 0.44; 95 % CI, 0.23 to 0.82; P = 0.01). Hospital readmissions (OR, 0.68; 95 % CI, 0.33 to 1.41; P = 0.30) and drug adherence rates (OR, 0.95; 95 % CI, 0.36 to 2.52; P = 0.29) were comparable between the groups. DOACs provide a safe and effective alternative to LMWH for postoperative thromboprophylaxis in gynecologic cancer surgeries. The significant reduction in CRNMB events suggests a potential safety advantage of DOACs.

Association of a CHEK2 somatic variant with tumor microenvironment calprotectin expression predicts platinum resistance in a small cohort of ovarian carcinoma

High-grade serous ovarian cancer (HGSOC) low overall survival rate is often attributed to platinum resistance. Recent studies suggest that the tumor associated-microenvironment (TME) is a determining factor in malignant tumor progression and DNA damage plays a crucial role in this process. Here, we sought to identify platinum resistance biomarkers associating the TME immune profile and the mutational landscape of the homologous repair pathway genes with the HGSOC patients prognosis and response to chemotherapy. Using a decision tree classifier approach, we found that platinum resistant (PR) patients were characterized by the presence of a novel deep intronic variant, the CHEK2 c.319+ 3943A &gt; T, and higher L1 expression (p =  0.016), (100% accuracy). Chek2 protein is an important component of DNA repair and L1, also known as calprotectin, is one component of the neutrophil extracellular traps (NETs) during inflammation, previously suggested as a key contributor to the metastatic process in HGSOC. Also, PD-L2 levels were significantly higher in PR patients positive for this CHEK2 variant (p =  0.048), underscoring the need to explore its potential therapeutic role for this cancer. Our results suggest an interplay between TME and DNA repair variants that results in a multifactorial nature of HGSOC resistance to platinum chemotherapy.

The path to elimination: FEBRASGO 2023's targeted strategies against cervical cancer in Brazil

Systemic Inflammatory Patterns in Ovarian Cancer Patients: Analysis of Cytokines, Chemokines, and Microparticles

Abstract Objective To compare the patterns of systemic inflammatory response in women with epithelial ovarian cancer (EOC) or no evidence of malignant disease, as well as to evaluate the profile of systemic inflammatory responses in type-1 and type-2 tumors. This is a non-invasive and indirect way to assess both tumor activity and the role of the inflammatory pattern during pro- and antitumor responses. Materials and Methods We performed a prospective evaluation of 56 patients: 30 women without evidence of malignant disease and 26 women with EOC. The plasma quantification of cytokines, chemokines, and microparticles (MPs) was performed using flow cytometry. Results Plasma levels of proinflammatory cytokines interleukin-12 (IL12), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) interleukin-1 beta (IL-1β), and interleukin-10 (IL-10), and C-X-C motif chemokine ligand 9 (CXCL-9) and C-X-C motif chemokine ligand 10 (CXCL-10) were significantly higher in patients with EOC than in those in the control group. Plasma levels of cytokine interleukin-17A (IL-17A) and MPs derived from endothelial cells were lower in patients with EOC than in the control group. The frequency of leukocytes and MPs derived from endothelial cells was higher in type-2 tumors than in those without malignancy. We observed an expressive number of inflammatory/regulatory cytokines and chemokines in the cases of EOC, as well as negative and positive correlations involving them, which leads to a higher complexity of these networks. Conclusion The present study showed that, through the development of networks consisting of cytokines, chemokines, and MPs, there is a greater systemic inflammatory response in patients with EOC and a more complex correlation of these biomarkers in type-2 tumors.