Eduardo Batista Cândido

Quality of life in women with vulvar cancer submitted to surgical treatment: a comparative study

OBJECTIVES To investigate the occurrence and severity of lymphoedema of the lower extremities (LLE), quality of life (QoL), and urinary and sexual dysfunction in women with vulvar cancer submitted to surgical treatment. STUDY DESIGN Twenty-eight patients with vulvar cancer submitted to vulvectomy and inguinofemoral lymphadenectomy and 28 healthy, age-matched women (control group) were evaluated. The occurrence and severity of LLE were determined by Millers Clinical Evaluation. QoL, urinary function and sexual function were assessed by the EORTC QLQ-C30, SF-ICIQ and FSFI questionnaires, respectively. The differences between groups and correlations were assessed using Students t-test, Chi-squared test, Mann-Whitney U-test and Spearmans rho test. RESULTS The groups were similar in terms of marital status, educational status, menopausal status, hormone therapy and height. The occurrence and severity of LLE were higher in women with vulvar cancer compared with the control group (p<0.001 and p = 0.003, respectively). A significant association was found between the severity of LLE and advanced age (p = 0.04), and the severity of LLE and higher body mass index (BMI; p = 0.04) in patients with vulvar cancer. In the patients with vulvar cancer, there was a significant correlation between the severity of LLE and worse QoL in the following domains: physical, cognitive, emotional, social, fatigue, pain, sleep and financial questions (p < 0.05). There was no difference in urinary function between the two groups (p = 0.113). Age and number of deliveries were the only variables associated with the occurrence of urinary incontinence (p = 0.01). Urinary incontinence was present in women with a mean age of 74.9 ± 4.6 years and a mean of 7.3 ± 1.3 normal deliveries. There was no difference between the groups in terms of the sexual function. Multivariate analysis showed an association between sexual function and age (p = 0.01), and sexual function and being in a stable relationship (p=0.02). CONCLUSION Patients submitted to vulvectomy or inguinofemoral lymphadenectomy for vulvar cancer are at higher risk of developing LLE compared with healthy, age-matched women. This has a negative effect on QoL, but does not interfere with urinary or sexual function.

Evaluation of N‐acetilglucosaminidase and myeloperoxidase activity in patients with endometriosis‐related infertility undergoing intracytoplasmic sperm injection

Aim:  Inflammation is as an important factor in ovulation with the active participation of leucocytes and their inflammatory mediators. The present study was performed to compare the activity of the inflammatory enzymes myeloperoxidase (MPO) and N‐acetylglucosaminidase (NAG) in patients with endometriosis‐related infertility and in normally ovulating women undergoing intracytoplasmic sperm injection (ICSI).

Immune Response Evaluation Through Determination of Type 1, Type 2, and Type 17 Patterns in Patients With Epithelial Ovarian Cancer

Innate and adaptive immune cells secrete different cytokines, which participate through distinct mechanisms in cell-mediated immunity and humoral immune responses. The aim of this study was to evaluate the immune response through analysis of type 1 (Th1), Th2, and Th17 cells in patients with epithelial ovarian cancer (EOC). Our study included 44 patients with EOC (study group) and 32 gynecological patients with no ovarian disease (control group). Fragments of ovarian tissue and blood samples were collected in both groups and aliquots of intracystic fluid and peritoneal fluid were recovered from the EOC patient group. Interleukin (IL)-2/IL-4/IL-6/IL-10/IL-17/tumor necrosis factor (TNF)-α/interferon (IFN)-γ levels were measured by cytometric bead array. Statistical analysis included chi-squared, Student t, Mann-Whitney, Kruskal-Wallis tests, and Cox regression model. Patients with EOC were associated with higher levels of TNF-α/IL-4/IL-6/IL-10 compared to the control group. Both IL-10 and TNF-α concentrations were higher in patients with stage III/IV EOC and also associated with higher levels of cancer antigen 125. Higher Th1-mediated immune response was observed when the cytoreduction was considered optimal. However, patients with EOC with unsatisfactory cytoreductive surgery and undifferentiated tumors were associated with higher concentrations of Th2 cytokines in the 4 sites studied. Higher IL-6/IL-10 and lower IFN-γ concentrations were also associated with a lower overall survival rate in patients with EOC. The EOC group presented a predominantly Th2 response and an immunosuppressant standard and had association between IL-6/IL-10/IFN-γ and prognosis.

Treatments for invasive carcinoma of the cervix: what are their impacts on the pelvic floor functions?

AIMS Describe the impact of surgery, radiotherapy and chemoradiation in the pelvic floor functions in cervical cancer patients. MATERIALS AND METHODS A prospective study with women submitted to radical hysterectomy (RH) (n = 20), exclusive radiotherapy (RT) (n = 20) or chemoradiation (CT/RT) (n = 20) for invasive cervical cancer. Urinary, intestinal and sexual function, as well as vaginal length and pelvic floor muscle contraction were evaluated. Comparisons between groups were performed by Kruskal-Wallis and Chi-square tests (p < 0.05). RESULTS The groups were similar in stress urinary incontinence incidence (p = 0.56), urinary urgency (p = 0.44), urge incontinence (p = 0.54), nocturia (p = 0.53), incomplete bowel emptying (p = 0.76), bowel urgency (p = 0.12) and soilage (p = 0.43). The CT/RT group presented a higher urinary frequency (p < 0.001) and diarrhea (p = 0.025). Patients in the RH group were more sexually active (p = 0.01) and experienced less dyspareunia (p = 0.021). Vaginal length was shorter in RT group (5.5 ± 1.9 cm) and CT/RT(5.3 ± 1.5 cm) than in the RH group (7.4 ± 1.1 cm) (p < 0.001). Pelvic floor muscle contraction was similar (p = 0.302). CONCLUSIONS RT and CT/RT treatment for cervical carcinoma are more associated to sexual and intestinal dysfunctions.

Association between Toll-like receptor and tumor necrosis factor immunological pathways in uterine cervical neoplasms

Introduction The immune system plays a critical role in the defense against human papillomavirus (HPV) infection and its persistence. Toll-like receptors (TLRs) are membrane receptors responsible for activation of the innate immune response, and an association between TLR expression and uterine cervical cancer has been shown. Tumor necrosis factors (TNFs) are among the main mediators of skin and mucosa inflammation. The aim of this study was to demonstrate the association between TLR and TNF immune expression and cervical cancer and premalignant cervical lesions. Methods A total of 64 embedded tissues were obtained from gynecological procedures, including 35 specimens with cervical intraepithelial neoplasia (CIN) and 10 specimens with cervical squamous cell carcinoma (CSCC) as well as 19 normal cervical samples. The expression of TLR2, TLR3, TLR4, TNF-α and TNF-β was measured by immunohistochemistry and graded into low and high levels of expression. Results There was an association between the expression levels of TLR2 and those of TNF-α and TNF-β (p = 0.01 and p = 0.021, respectively) in the cervical cancer and CIN groups. TLR4 expression was associated with TNF-α and TNF-β expression (p = 0.016 and p = 0.025, respectively) in these 2 groups. By contrast, TLR3 was not statistically associated with TNF-α or TNF-β in any of the groups. Conclusions There might be an association of the TLR2 and TLR4 pathways with the immunological response of TNF-α and TNF-β in cervical cancer. These markers are also expressed at higher levels in cervical cancer and premalignant lesions compared to normal controls.

Non-hormonal and hormonal intrauterine contraception: survey of patients perceptions in four Latin American countries.

ABSTRACT Objectives: This study sought to understand women’s perceived barriers to the use of hormonal and non-hormonal intrauterine contraception in Latin America. Methods: We developed an online survey for women in Argentina, Brazil, Colombia and Mexico who were seeking contraception. The questions aimed at evaluating patient awareness of negative stories and statements, as well as perceived barriers to the copper intrauterine device (IUD) and the levonorgestrel-releasing intrauterine system (LNG-IUS). Results: The survey was mailed to 2300 women. A total of 1953 responses were received from Argentina (n = 465), Brazil (n = 380), Colombia (n = 613) and Mexico (n = 495). More women reported having heard negative stories about the copper IUD than about the LNG-IUS. More women believed that the copper IUD, rather than the LNG-IUS, was suitable only for those who had already had children. More women believed that weight gain (14.3% vs. 38.2%; p < 0.001), mood swings (14.1% vs. 38.7%; p < 0.001) and infertility (16.3% vs. 19.9%; p = 0.016) were possible side effects of the LNG-IUS. By contrast, more women believed that abortion (36% vs. 22.7%; p < 0.001), pelvic infections (42.1% vs. 15.7%; p < 0.001) and ectopic pregnancy (43.5% vs 23.5%; p < 0.001) were side effects more associated with the copper IUD. More believed the copper IUD was associated with less pain during placement and removal compared with the LNG-IUS (42.8% vs. 31.2%; p < 0.001). The perception of increased risk of contracting a sexual transmitted disease did not differ between the methods (IUD vs. LNG-IUS, 21.7% vs. 20.3%; p = 0.388). Conclusions: Respondents to a web-based survey in four Latin American countries have misperceptions regarding the adverse effects and risks of intrauterine contraception, which may hamper the use of these safe and efficient contraceptive methods. Education about the true risks and benefits involved is fundamental to improving patient acceptance and compliance as well as reducing unplanned pregnancies and unsafe abortions.

Gene expression profile of ABC transporters and cytotoxic effect of ibuprofen and acetaminophen in an epithelial ovarian cancer cell line in vitro.

PURPOSES To determine the basic expression of ABC transporters in an epithelial ovarian cancer cell line, and to investigate whether low concentrations of acetaminophen and ibuprofen inhibited the growth of this cell line in vitro. METHODS TOV-21 G cells were exposed to different concentrations of acetaminophen (1.5 to 15 μg/mL) and ibuprofen (2.0 to 20 μg/mL) for 24 to 48 hours. The cellular growth was assessed using a cell viability assay. Cellular morphology was determined by fluorescence microscopy. The gene expression profile of ABC transporters was determined by assessing a panel including 42 genes of the ABC transporter superfamily. RESULTS We observed a significant decrease in TOV-21 G cell growth after exposure to 15 μg/mL of acetaminophen for 24 (p=0.02) and 48 hours (p=0.01), or to 20 μg/mL of ibuprofen for 48 hours (p=0.04). Assessing the morphology of TOV-21 G cells did not reveal evidence of extensive apoptosis. TOV-21 G cells had a reduced expression of the genes ABCA1, ABCC3, ABCC4, ABCD3, ABCD4 and ABCE1 within the ABC transporter superfamily. CONCLUSIONS This study provides in vitro evidence of inhibitory effects of growth in therapeutic concentrations of acetaminophen and ibuprofen on TOV-21 G cells. Additionally, TOV-21 G cells presented a reduced expression of the ABCA1, ABCC3, ABCC4, ABCD3, ABCD4 and ABCE1 transporters.

Cirurgia não ginecológica em pacientes com câncer de ovário

OBJECTIVE: to evaluate the incidence of non-gynecological surgical procedures used in the treatment of ovarian cancer, as well to describe their complications. METHODS: eighty-two patients with ages from 22 to 89 (mean = 54.1 ± 15.1 years), submitted to laparotomy for surgical treatment of ovarian cancer from February 1999 to October 2003 were retrospectively evaluated. This study included only patients with epithelial ovary carcinoma. The patients were divided into 2 groups, patients submitted exclusively to gynecological procedures and patients submitted to non-gynecological procedures. Statistical analysis was made with the Students t-test or the chi-square test. RESULTS: 5 patients (6.1%) were in stage (FIGO) I, 18 (21.9%) in stage II, 40 (48.8%) in stage III, and 19 (23.2%) in stage IV. Non-gynecological procedures were done in 35 cases (42.7%), including: 17 colostomies, 16 enterectomies, 8 peritonectomies, 7 colectomies, 5 partial diaphragm resections, 4 partial cystectomies, 4 splenectomies, 2 ileostomies, and 1 hepatectomy. All patients submitted to non-gynecological procedures were included in stages III and IV. This group of patients underwent longer-lasting surgeries (5.3 ± 1.4 versus 3.1 + 0,0 h; p < 0.001). There was no significant difference between these two groups regarding hemotransfusion requirement (42,2 versus 40%; p = 0.512) and hospitalization time (11.5 ± 7.2 versus 10 ± 9.9 days; p = 0.454). Patients submitted to non-gynecological surgeries developed higher rates of postoperative complications (37 versus 17.1%; p = 0.042), and two of them (2.4%) died. CONCLUSION: non-gynecological surgical procedures are frequently used in the treatment of patients with ovarian cancer. These procedures are associated with a longer-lasting surgery and higher rates of postoperative complications.

PTEN expression in patients with carcinoma of the cervix and its association with p53, Ki-67 and CD31

PURPOSE To investigate protein expression and mutations in phosphatase and tensin homolog (PTEN) in patients with stage IB cervical squamous cell carcinoma (CSCC) and the association with clinical-pathologic features, tumor p53 expression, cell proliferation and angiogenesis. METHODS Women with stage IB CSCC (n=20 - Study Group) and uterine myoma (n=20 - Control Group), aged 49.1±1.7 years (mean±standard deviation, range 27-78 years), were prospectively evaluated. Patients with cervical cancer were submitted to Piver-Rutledge class III radical hysterectomy and pelvic lymphadenectomy and patients in the Control Group underwent vaginal hysterectomy. Tissue samples from the procedures were stained with hematoxylin and eosin for histological evaluation. Protein expression was detected by immunohistochemistry. Staining for PTEN, p53, Ki-67 and CD31 was evaluated. The intensity of PTEN immunostaining was estimated by computer-assisted image analysis, based on previously reported protocols. Data were analyzed using the Students t-test to evaluate significant differences between the groups. Level of significance was set at p<0.05. RESULTS The PTEN expression intensity was lower in the CSCC group than in the Control (benign cervix) samples (150.5±5.2 versus 204.2±2.6; p<0.001). Our study did not identify any mutations after sequencing all nine PTEN exons. PTEN expression was not associated with tumor expression of p53 (p=0.9), CD31 (p=0.8) or Ki-67 (p=0.3) or clinical-pathologic features in patients with invasive carcinoma of the cervix. CONCLUSIONS Our findings demonstrate that the PTEN protein expression is significantly diminished in CSCC.

Heavy menstrual bleeding: a global survey of health care practitioners’ perceptions

Objectives: This study sought to assess the perceptions of health care practitioners (HCPs) regarding heavy menstrual bleeding (HMB).Methods: We developed an online survey for HCPs administered in ...Abstract Objectives: This study sought to assess the perceptions of health care practitioners (HCPs) regarding heavy menstrual bleeding (HMB). Methods: We developed an online survey for HCPs administered in 10 countries (Brazil, Canada, China, France, Germany, Korea, Russia, Spain, UK and USA), in order to assess their perceptions regarding HMB. Results: We received 1032 responses. Most HCPs considered more than 7 days of bleeding abnormal. There was a significant difference in the definition of HMB between countries (p < .001). Most HCPs measured menstrual blood loss by the number of sanitary pads or tampons needed, followed by the impact on patients’ daily activities. The majority of HMB patients (61%) were diagnosed as having a non-structural disorder with no causative identifiable coagulopathy. Patient acceptance and compliance were each relevant for the treatment decisions of half of the HCPs. Treatment options for idiopathic HMB featured mainly oral contraceptives and the levonorgestrel-releasing intrauterine system. Surgery was mentioned as a treatment option for idiopathic HMB by 44% of HCPs. Conclusion: The definition of HMB and HCP perceptions of HMB regarding diagnostic and therapeutic issues varied between countries. Surgery was mentioned as a treatment for idiopathic HMB by nearly half of HCPs. Clinician education is greatly needed to improve the management of women with HMB.