Rosekeila Simões Nomelini

Management of ultrasonographic endometrial thickness in postmenopausal asymptomatic women

Immunostaining of stromal CD56 cells in ovarian malignancies

The aim of this study was to evaluate CD56 immunostaining in the stroma of benign and malignant ovarian epithelial neoplasms and associate the CD56 immunostaining with prognostic factors and survival in ovarian cancer. Patients with ovarian epithelial neoplasia (n=77) were studied with a prospective cohort. The CD56 immunostaining was evaluated in the peritumoral stroma. Two groups were evaluated: benign ovarian neoplasms (n=40) and malignant ovarian neoplasms (n=37). Data were recorded for histological type and grade, International Federation of Gynecology and Obstetrics staging, molecular subtype, and lymph node metastases. Fisher's exact test and Kaplan-Meier survival curves were used, with a significance level of ≤0.05. We found greater CD56 stromal immunostaining in malignant neoplasms when compared to the group of benign neoplasms (p=0.00001). There was no significant difference in relation to the prognostic factors and survival. Malignant ovarian neoplasms showed higher stromal CD56 immunostaining. As the prognostic value of natural killer in ovarian cancer is controversial, knowing the specific function of each cell present both in the tumor tissue and systemically may help guide successful immunotherapies in the near future.

IL6, IL8, and IL10 in the distinction of malignant ovarian neoplasms and endometriomas

AbstractProblemStudies have shown a relationship between endometriosis and ovarian cancer. Our aims were to evaluate and compare the dosages of cytokines IL‐2, IL‐5, IL‐6, IL‐8, IL‐10, and TNF‐α in serum, intracystic fluid, and peritoneal fluid of patients with ovarian endometrioma, malignant and benign ovarian neoplasms, and non‐neoplastic ovarian tumors; to verify if there is a correlation between the values of these cytokines between ovarian endometrioma and ovarian malignancy; and to determine the best cut‐off point for serum cytokines that can be used to differentiate patients with ovarian malignancy and endometrioma.Method of studyThe concentrations of cytokines were quantified by enzyme‐linked immunosorbent assay (ELISA), analyzed by Kruskal‐Wallis test with the Dunn post‐test. Receiver operating feature (ROC) curve was used to obtain the area under the curve (AUC) and to determine the best cut‐off values that could be used in the diagnosis of ovarian malignancy. Correlations of cytokine concentrations were performed by the Spearman test.ResultsIL‐6, IL‐8, and IL‐10 concentrations were higher in patients with malignant neoplasia. When evaluating the area under the curve (AUC) of serum cytokine levels comparing patients with malignant neoplasia and endometriomas, there was statistical significance for IL‐6, IL‐8, and IL‐10.ConclusionOur results showed utility in serum concentrations of IL‐6, IL‐10, and IL‐8 as parameters that differentiate endometriomas from ovarian malignancies.

Serum cytokines and CXCR2: potential tumour markers in ovarian neoplasms

The aim was to investigate the systemic levels of cytokines and the expression of the chemokine receptor CXCR2 in circulating neutrophils in patients with non-neoplastic ovarian lesions, benign neoplasia or malignant neoplasia. Controls and patients with ovarian tumours were pre-operatively compared for the production of cytokines (IL-2, IL-5, IL-6, IL-8, IL-10 and TNF-α) by ELISA, and for the expression of the chemokine receptor, CXCR2, in neutrophils, by flow cytometry. Randomly selected patients within the malignant group were re-evaluated for the inflammatory parameters at 30 days after surgery. The serum concentrations of IL-6, IL-8 and IL-10 were significantly higher in the benign and malignant neoplasia than in the control group, and their levels were significantly higher in ovarian cancer patients than in patients with non-neoplastic tumours or benign neoplasia. Treatment reduced IL-8 serum levels but did not affect CXCR2 expression in neutrophils. Cut-off values for IL-6, IL-8, and IL-10 comparing malignant vs. benign neoplasia were 11.3, 71.7, 14.8, and comparing malignant neoplasm vs. non-neoplastic lesions were 7.2, 43.5, 12.3, respectively. Serum IL-6, IL-8, and IL-10 levels, and expression of CXCR2 in circulating neutrophils seem promising for distinguishing ovarian cancer patients from patients with benign tumours.

Endometriosis: What is the Influence of Immune Cells?

The Role of Stroma in Ovarian Cancer

Laboratory predictors of survival in ovarian cancer

SUMMARY OBJECTIVE To relate disease-free survival and overall survival with type I and type II ovarian cancer and preoperative laboratory parameters biomarkers. METHODS A retrospective study was carried out based on the collection of data from medical records of patients with ovarian tumors. Kaplan-Mayer curves were drawn based on the statistical analysis of the data and were compared using the Log-rank test. RESULTS Disease-free survival in type I ovarian cancer was significantly higher than in type II (p=0.0013), as well as in those with normal levels of CA-125 (p=0.0243) and with a platelet-lymphocyte ratio (PLR) lower than 200 (p=0.0038). The overall survival of patients with type I ovarian cancer was significantly higher than in patients with type II, as well as in patients with normal CA-125 serum levels (p=0.0039) and those with a preoperative fasting glucose of less than 100 mg/dL. CONCLUSION CA-125 levels may predict greater overall and disease-free survival. PLR < 200 may suggest greater disease-free survival, whereas normal fasting glucose may suggest greater overall survival.

IL-6 and IL-8 as Prognostic Factors in Peritoneal Fluid of Ovarian Cancer

The objectives of the study were to analyze the dosage of a cytokine panel (IL2, IL5, IL6, IL8, IL10, and TNF-α) in the peritoneal fluid and relate the dosage of these cytokines to prognostic para- meters and survival in ovarian cancer. Peritoneal fluid was collected intraopera- tively from 29 patients with primary malignant ovarian neoplasia. Cytokine panel dosing was performed with ELISA. Comparisons of cytokines with prognostic factors were performed using the Wilcoxon-Mann-Whitney test. ROC curves were used to determine the cutoff value of NLR, PLR, and IL6. Univariate and multivariate analysis of disease-free survival (DFS) or overall survival (OS) were performed (Kaplan-Meier and Cox regression). The differences were considered significant when the value of p 3.18 (p = .04), a platelet-lymphocyte ratio (PLR) >219.23 (p = .0051), CA-125 levels >35 U/mL (p = .0019), stage IIIC (p = .0203), and DFS ≤ 24 months (p = .0267). For IL-8, higher levels were related to PLR > 219.23 (p = .0426), and CA-125 >35 U/mL (p = .0292). In the univariate analysis, IL-6 levels ≥87.23 in peritoneal fluid had a relationship with shorter DFS at significance threshold (p = .05), and with a shorter OS (p = .039). Multivariate survival analysis proved that IL-6 level in the peritoneal fluid was an independent predictor of OS. Therefore, IL-6 and IL-8 in peritoneal lavage were related to poor prognostic factors. These cytokines may represent new biomarkers for ovarian cancer therapies.

Lymphocytes in Peritumoral Stroma: Evaluation in Epithelial Ovarian Neoplasms

Role of biomarkers CA-125, CA-15.3 and CA-19.9 in the distinction between endometriomas and ovarian neoplasms

To evaluate the utilisation of CA-125, CA-15.3 and CA-19.9 in differentiating between ovarian neoplasms and endometriomas, and the best cut-off value for these tumour markers in this differentiation. Preoperative serum values of CA-125, CA-15.3 and CA-19.9 were evaluated in 265 patients undergoing surgery for adnexal masses, being 32 non-neoplastic lesions, 134 benign neoplasms, 19 borderline tumours, 36 malignant neoplasms, and 44 endometriomas. ROC curves and Univariate and multivariate analyses were performed. Only CA-19.9 was useful in differentiating between endometriomas and ovarian neoplasms (benign and malignant tumours), being this marker found at higher levels in endometriomas. In multivariate analyses, CA-19.9 greater than 22.3 U/mL was considered an independent factor for the diagnosis of endometrioma, comparing endometrioma and ovarian cancer. Comparing endometrioma and all other groups, the clustering analysis using the combination CA-125 > 34.28 U/mL and CA-19.9 > 19.12 U/mL demonstrated that this association was considered an independent factor for the diagnosis of endometrioma. CA-9.9 is useful in distinguishing between endometriomas and ovarian cancer, and its combination with CA-125 is useful in differentiating endometrioma from other ovarian lesions.

Mast cells and M2 macrophages in ovarian cancer

The objectives of this study were to investigate the immunohistochemical expression of markers of mast cells and M2 macrophages in benign and malignant ovarian neoplasms and to examine the prognostic value of this expression in ovarian cancer. The study was performed with samples from 32 patients, divided into benign (

Laboratory parameters as predictors of prognosis in uterine cervical neoplasia

The aims of study were to assess platelet counts, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), RWD (red cells distribution width) and fasting glucose in patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer; and to relate these parameters to prognostic factors and survival in cervical cancer. We evaluated the patients with confirmed diagnosis of invasive cervical cancer (n = 102), and CIN (n = 102). Histological type, NLR, PLR, RDW, platelets count, fasting glucose, staging, overall survival (OS), and disease-free survival (DFS) were evaluated. The results of laboratory parameters were assessed by Mann-Whitney test. A receiver operating characteristic (ROC) curve was used to determine the best cut-off values. Survival was verified by the Kaplan-Meyer method followed by the Gehan-Breslow test. Multivariate analysis was performed using Cox regression. The level of significance was less than 0.05. Comparing CIN and invasive malignancies, higher values of NLR, PLR, RDW and fasting glucose were found in cancer patients (p < 0.0001, p = 0.011, p = 0.0153 and p = 0.0096, respectively). In cervical cancer, higher NLR and PLR values were found at stage II to IV when compared to stage I (p = 0.0066 and p = 0.005, respectively). ROC curves were performed. In invasive neoplasms, the cut-off values for NLR and PLR in the comparison between stage I and greater than I were 4 and 165.45, respectively. For survival curves, there was lower OS and DFS in patients with NLR greater than 4 (p = 0.0004 and p = 0.0153, respectively) and PLR greater than 165.45 (p = 0.0319 and p = 0.0362, respectively). After multivariate analysis, only NLR remained as an independent factor in DFS (HR = 6.095, 95 % CI = 1.120-33.177, p = 0.037) and OS (HR = 4.522, 95 % CI = 1.241-16.479, p = 0.022) CONCLUSION: Higher NLR is associated to lower OS and DFS in invasive uterine cervical neoplasia, and can be considered an independent factor of worse prognosis.

CIN Extension at Colposcopy: Relation to Treatment and Blood Parameters

To determine the colposcopic lesion size that predicts the presence of residual lesion in patients with cervical intraepithelial neoplasia (CIN) 2/3, to aid gynaecologists in selecting conservative management. Data from 51 patients with low- and high-grade squamous intraepithelial lesions were evaluated. Colposcopic images were captured and lesion areas were calculated. Polymerase chain reaction (PCR) for human papillomavirus was performed. Laboratory parameters were evaluated. Receiver operating characteristic (ROC) curves were used to obtain cut-off values for lesion area. The performance of PCR in the detection of high-grade CIN was assessed. A flowchart was created to compare the costs of related procedures in the Brazilian health system. For CIN 2/3 treated with excisional surgery, the best cut-off value for lesion area below which no residual lesion was present was 21 019 pixels CIN reflects systemic alteration, leading to altered NLRs, PLRs, and absolute numbers of leukocytes. Patients with high-grade CIN and colposcopic lesion areas <21 019 pixels

Association of lesion area measured by colposcopy and cervical neoplasia

Studies have demonstrated that the size of lesion in colposcopic imaging can be associated with the grade of CIN. We evaluated 36 patients and at the time of colposcopy, the images were recorded and analysed for lesion area measurement. A ROC curve was used to obtain the area under the curve and to determine the best cut-off values between area lesion (pixels

Absolute band neutrophils count is a predictor of overall survival in advanced uterine cervical cancer

Neutrophils play a role during the oncogenic process, and their count can be a prognostic marker. The objective was to evaluate the association of band and segmented neutrophils with prognostic factors, overall survival, and disease-free survival in advanced uterine cervical cancer (IIB to IVB staging). This study evaluated 88 patients diagnosed with uterine cervical cancer staging IIB to IVB. The recorded data from medical records were age, parity, staging, histological type, absolute count of total neutrophils, band neutrophils and segmented neutrophils, disease-free survival, and overall survival. Receiver-operating characteristic (ROC) curve was used to obtain the area under the curve (AUC) and determine the best cut-off values for each parameter. Survival was verified by the Kaplan-Meier method, and multivariate analysis was performed by Cox regression. The level of significance was ≤ 0.05. Regarding the total neutrophils, band, and segmented neutrophils count, a cut-off value of 6187/mm The absolute count of band neutrophils greater than 273/mm

Blood count and fasting blood glucose level in the assessment of prognosis and survival in advanced cervical cancer

The objective of this study was to verify whether the parameters of the blood count and the fasting glucose level before treatment are related to prognosis and survival in cervical cancer (IIB-IVB staging). Patients with cervical cancer (stages IIB-IVB) were evaluated (n=80). Age, parity, staging, histological grade, histological type, hemoglobin, red blood cells, hematocrit, neutrophil, lymphocyte and platelet counts, red blood cell distribution width, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, fasting glucose levels, overall survival, and disease-free survival were evaluated. The results of laboratory parameters were compared using the Mann-Whitney U test. Receiver operating characteristic curve was used to obtain the area under the curve and determine the best cutoff values for each parameter. Survival was verified by using the Kaplan-Meier method, followed by the log-rank test. The level of significance was ≤0.05. Regarding staging, lower hemoglobin values (p=0.0013), red blood cells (p=0.009), hematocrit (p=0.0016), higher leukocytes (p=0.0432), neutrophils (p=0.0176), platelets (p=0.0140), red blood cell distribution width (RDW) (p=0.0073), neutrophil-lymphocyte ratio (p=0.0039), platelet-lymphocyte ratio (p=0.0006), and fasting glucose level (p=0.0278) were found in IIIA-IVB compared with IIB staging. Shorter disease-free survival was associated with hemoglobin ≤12.3 g/dl (p=0.0491), hematocrit ≤38.5% (p=0.05), neutrophil-lymphocyte ratio >2.9 (p=0.0478), and platelet-lymphocyte ratio >184.9 (p=0.0207). Shorter overall survival was associated with hemoglobin ≤12.3 g/dl (p=0.0131), hematocrit ≤38.5% (p=0.0376), neutrophil-lymphocyte ratio >2.9 (p=0.0258), and platelet-lymphocyte ratio >184.9 (p=0.0038). The analysis of these low-cost and easily accessible parameters could be a way to monitor patients in order to predict treatment failures and act as early as possible.

Evaluation of cytokine immunostaining in ovarian neoplasms and endometriomas

The objective of our study was to quantify and compare the immunostaining of IL-2, IL-5, IL-6, IL-8, and TNF-α in endometriomal tissue, non-neoplastic tumors, benign neoplasms, and malignant ovarian neoplasms. The study involved 90 patients: 15 non-neoplastic ovarian lesions, 28 ovarian benign neoplasms, 28 ovarian malignant neoplasms, and 19 ovarian endometriomas were diagnosed. Immunohistochemistry was performed for cytokines IL-2, IL-5, IL-6, IL-8, and TNF-α and their concentrations were compared in these groups. Fisher's exact test was used, requiring a P-value of < 0.05 for significance. IL-5 and IL-8 epithelial immunostaining is stronger in endometriomas than in ovarian cancer (P-values of 0.0046 and 0.0149, resp.). The stromal immunostaining of TNF-α, IL-5, IL-6, and IL8 is stronger in endometriomas than in ovarian cancer (P-values of 0.0008, < 0.0001, 0.0003, and 0.0006, resp.). Stronger immunostaining of some cytokines in endometriomas compared to ovarian cancer reflects an inflammatory and immune response that could be future targets for new discoveries about the infiltrative behavior of endometriosis.

Peritumoral stroma and systemic inflammatory response in cervical cancer

Objective: To compare cervical stroma in advanced cervical cancer with the control group; to compare, in the pre-treatment period, hemogram parameters in patients with advanced cervical cancer with the same parameters as the control group; and to verify if there is an association of stromal markers with prognostic factors in cervical cancer. Materials and methods: We prospectively evaluated 16 patients diagnosed with advanced invasive cervical cancer. A control group of 22 patients was used (uterine leiomyoma). Immunohistochemistry was performed to verify the stromal immunostaining of alpha-smooth muscle actin (SMA) and fibroblast activation protein alpha (FAP). Immunostainings and hemogram parameters were compared using Fisher's exact and Mann-Whitney Test, respectively. Results: Strong FAP immunostaining was more frequent in patients with cervical cancer when compared with patients with leiomyoma (P = 0.0002). Regarding SMA, strong immunostaining was also found more in the group of cancer patients compared to the control group (P &lt; 0.00001). The neutrophil-lymphocyte ratio (NLR) values were higher in the cancer patient group compared to the control group (P = 0.0019). There was no association of the parameters studied with prognostic factors. Conclusions: Strong FAP and SMA immunostaining was found more in patients with cervical cancer when compared to the control group. NLR values were also higher in cervical cancer. Key words: uterine cervical neoplasms – alpha-smooth muscle actin – fibroblast activation protein alpha – blood cell count