Rosekeila Simões Nomelini

Early diagnosis and predictors of malignancy of adnexal masses

Purpose of review Ovarian cancer is an important cause of death among women with a malignant gynecological tumor. Cure rates for the disease at an early stage are around 80–90%, but survival is only 50% as the majority of women already show advanced disease upon diagnosis. The combination of gynecological examination, ultrasonography, and systemic tumor marker assay is considered to be a good strategy for the early diagnosis of ovarian neoplasia. Recent findings Today, new technologies such as ultrasonography and tumor marker assay have increased the diagnosis rate for adnexal masses. These non-invasive methods, however, frequently do not distinguish benign conditions from malignant ones, which results in unnecessary surgery. Transvaginal ultrasonography is useful for diagnosing adnexal masses, but benign and malignant adnexal masses can present similar morphological characteristics. Combination with color Doppler ultrasonography and/or tumor markers may improve the accuracy of the method. Gene-expression array, proteomics and mathematical models form new approaches, but proper prospective studies are needed to validate them. Summary The techniques of pelvic examination, ultrasonography, color Doppler ultrasonography, and tumor markers can be indicated for the diagnosis of ovarian cancer. The differentiation between benign and malignant ovarian tumor is, however, a clinical challenge. Until better diagnostic methods become available, patients and their physicians can use these techniques to decide on management.

Production of Nitric Oxide and Expression of Inducible Nitric Oxide Synthase in Ovarian Cystic Tumors

Tumor sections from nonneoplastic (n = 15), benign (n = 28), and malignant ovarian tumors (n = 20) were obtained from 63 women. Immunohistochemistry of the tumor sections demonstrated that inducible nitric oxide synthase (iNOS) expression was increased in ovarian cancer samples compared to nonneoplastic or benign tumor samples. Using the Griess method, nitric oxide (NO) metabolite levels were also found to be elevated in malignant tumor samples compared to benign tumor samples (P < .05). For stage I ovarian cancer, intracystic NO levels >80 μM were more frequent than NO levels <80 μM, and iNOS expression in well-differentiated carcinomas was greater than in moderately/poorly differentiated carcinomas (P < .05). These data suggest an important role for NO in ovarian carcinogenesis.

Utilization of human papillomavirus testing for cervical cancer prevention in a university hospital

This study aimed to evaluate the performance and cost of using polymerase chain reaction (PCR) and hybrid capture in the detection of cervical intraepithelial neoplasia (CIN) in patients with cytological abnormalities (ASCUS/low-grade squamous intraepithelial lesion--LSIL), and the feasibility of implementing these methods in Brazils Unified National Health System (SUS). Colposcopy gave a negative predictive value of 92.86% and efficiency of 87.8% for diagnosing CIN. The sensitivity of PCR and hybrid capture for detecting CIN was 83.33% and 66.67%, respectively, and the negative predictive value for diagnosing CIN2/CIN3 was 100% and 94.74%, respectively. The annual cost for 80 patients was lower when all patients with ASCUS/LSIL were referred for colposcopy than when HPV testing was performed and those with positive results were referred for colposcopy. Therefore, at present, it is financially unfeasible for the National Health System to implement HPV testing to screen patients with cytological abnormalities (ASCUS/LSIL). However, considering that large-scale use might make such methods cheaper, PCR should be the chosen method, since it is less expensive, more sensitive, and has a high negative predictive value.

Immunohistochemical staining of tumor necrosis factor-α and interleukin-10 in benign and malignant ovarian neoplasms

Ovarian cancer is the ninth most common malignancy and the fifth leading cause of cancer death in women in the USA. The majority of malignant tumors of the ovary are diagnosed at an advanced stage, making it the most fatal gynecological cancer. The aim of the current study was to determine whether there are differences in immunohistochemical tissue staining of cytokine tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) between benign tumors and malignant primary ovarian cancer. In total, 28 patients undergoing surgery for ovarian cysts were evaluated, and a diagnosis of benign neoplasm (n=14) or malignant neoplasm (n=14) was determined. An immunohistochemical study of histological sections of ovarian tumors was conducted. The results were analyzed using Fisher’s exact test, with P<0.05 indicating a statistically significant difference. Immunohistochemical staining of IL-10 was increased in malignant tumors compared with benign tumors (P=0.0128). For TNF-α, the immunohistochemical staining was more intense in malignant neoplasms, however, a statistically significant difference was not observed. These results indicate that the analysis of cytokines may be useful as a potential tissue marker of ovarian malignancy.

Serous papillary cystadenocarcinoma in supernumerary ovary

Case report A 64-year-old woman sought the gynaecological service with ultrasonography, showing a well-defi ned heterogeneous tumour with thick walls, Doppler resistive index 0.79 and volume 942 ml. At surgery, there was a 1,250 g retrouterine mass (Figure 1) and eutopic atrophic ovaries. Th e fallopian tubes were normal. Th e mass was resected. Histopathology diagnosed a serous papillary cystadenocarcinoma in a supernumerary ovary (Figure 2a). Immunohistochemistry showed positive antibody staining with CA125, emphasising the diagnosis (Figure 2b). Primary papillary serous carcinoma of the peritoneum was excluded because the lesion was cystic and there was a corpus albicans. Hysterectomy, bilateral oophorectomy, omentectomy and pelvic lymphadenectomy were performed. Th ere was no residual tumour. Th ere was no evidence of other congenital urogenital tract abnormalities.

Parameters of blood count and tumor markers in patients with borderline ovarian tumors: a retrospective analysis and relation to staging.

The aim of this paper was to evaluate the parameters of blood count and tumor markers in borderline ovarian tumors. We evaluated 21 patients who had confirmed histopathologic diagnosis of borderline ovarian tumor. We recorded age, parity, tumor type, stage of cancer, serum levels of tumor markers (CA-125, CA-15.3, CA-19.9, CEA, AFP), and the parameters of blood count, fasting glucose, disease-free survival and overall. The patients were divided into two groups, stage IA (n = 13) and stage IB-IIIC (n = 8). The unpaired t-test and Fishers exact test were used, with P values of less than 0.05 being considered to indicate statistical significance. Levels of red blood cells, hematocrit, and hemoglobin were significantly higher in stage IA when compared with stage IB-IIIC (P < 0.05). The levels of tumor marker CEA had a tendency to be higher in the group stage IB-IIIC (0.08). Abnormal levels of CEA and CA-19.9 were found more frequently in stages IB-IIIC. Therefore, parameters of blood count, CEA, and CA-19.9 should be targeted for further research in identifying prognostic factors in borderline tumors.

Serum IL-6 and IL-8 Correlate with Prognostic Factors in Ovarian Cancer

ABSTRACT The aim of the study was to correlate serum levels of IL-2, IL-5, IL-6, IL-8, IL-10, and TNF-α with clinical, laboratory, and pathological prognostic factors in patients with primary ovarian malignancy. Patients treated at the Pelvic Mass Ambulatory of the Discipline of Gynecology and Obstetrics/Oncology Research Institute (IPON) of the UFTM with confirmed diagnosis of malignant ovarian neoplasia (n = 26) were evaluated. Serum collection was performed preoperatively for the determination of tumor markers. The cytokines IL-2, IL-5, IL-6, IL-8, IL-10, and TNF-α were assayed by enzyme-linked immunosorbent assay (ELISA). The prognostic factors were compared using the Mann-Whitney test, with significance level lower than 0.05. When evaluating IL6, it was observed that higher serum levels were associated with overall survival less than 60 months (p = 0.0382). In the evaluation of IL8, higher serum levels were associated with neutrophil-to-lymphocyte ratio (NLR) ≥ 4 and platelet-to-lymphocyte ratio (PLR) ≥ 200 (p = 0.0198 and p = 0.0072, respectively), altered values of serum CA125 (p = 0.0457), and stage IIIC (p = 0.0486). Therefore, increased levels of IL-6 and IL-8 are associated with factors of worse prognosis in ovarian cancer. Additional studies with a larger sample of patients are needed to confirm the role of cytokines as prognostic factors, in the definition of treatment, and in the development of future target therapies.

Predicting Functional Capacity From Measures of Muscle Mass in Postmenopausal Women

Menopause increases body fat and decreases muscle mass and strength, which contribute to sarcopenia. The amount of appendicular muscle mass has been frequently used to diagnose sarcopenia. Different measures of appendicular muscle mass have been proposed. However, no studies have compared the most salient measure (appendicular muscle mass corrected by body fat) of the appendicular muscle mass to physical function in postmenopausal women.

Helper T Lymphocyte Response in the Peripheral Blood of Patients with Intraepithelial Neoplasia Submitted to Immunotherapy with Pegylated Interferon-α

Immunotherapy in cancer patients is a very promising treatment and the development of new protocols and the study of the mechanisms of regression is imperative. The objective of this study was to evaluate the production of cytokines in helper T (CD4+) lymphocytes during immunotherapy with pegylated IFN-α in patients with cervical intraepithelial neoplasia (CIN). We conducted a prospective study with 17 patients with CIN II-III using immunotherapy with pegylated IFN-α subcutaneouly weekly, and using flow cytometry we evaluated the peripheric CD4+ T lymphocytes. The results show that in the regression group the patients presented a significant increase in the amount of IFN-γ during the entire immunotherapy, compared with the group without a response. The amount of CD4+ T lymphocytes positive for IL-2, IL-4, IL-10 and TGF-β is significantly lower in patients with good clinical response. The results also demonstrate that patients with regression have a higher amount of intracellular TNF-α in CD4+ T lymphocytes before the start of treatment. Analyzing these data sets, it can be concluded that immunotherapy is a viable clinical treatment for patients with high-grade CIN and that the regression is dependent on the change in the immune response to a Th1 pattern.

Correlation of cytokines and inducible nitric oxide synthase expression with prognostic factors in ovarian cancer

The study related the immunohistochemical staining of cytokines (IL2, IL5, IL6, IL8, IL10, and TNF-alpha), and iNOS staining with clinical and pathological parameters of patients with primary ovarian malignancy. We prospectively evaluated 40 patients who underwent surgical treatment in accordance with pre-established criteria and later confirmed diagnosis of ovarian cancer. Immunohistochemistry study for cytokines (IL2, IL5, IL6, IL8, IL10, TNF-alpha) and iNOS was performed. The evaluation of prognostic factors was performed using the Fishers exact test. The significance level was less than 0.05. Histological grade 1 was significantly correlated with strong intensity for TNF-α (p=0.0028). In addition, early stages showed strong expression intensity of TNF-α, but this was at the limit of significance (p=0.0525). Strong staining immunohistochemical IL5 was related to disease-free survival less than or equal to 24 months, suggesting that a factor of poor prognosis, but there was no statistical significance (p=0.1771). There was no statistical significance in relation at other cytokines studied. Therefore, immunohistochemical staining in strong intensity for TNF-α was related to histological grade 1 and early stages of ovarian cancer in our sample of patients.