Stromal IL2 is related to the neutrophil/lymphocyte ratio in epithelial ovarian cancer.

INTRODUCTION: There is a need for the development of new biomarkers for diagnosis and prognosis of ovarian cancer, which can ideally serve as targets for new therapeutic modalities and individualization of treatment. The objectives of this study were to determine the prognostic significance of the neutrophil/lymphocyte ratio in the peripheral blood of patients with ovarian cancer and tumor staging, and to associate this marker with the immune expression of a panel of cytokines. METHODS: The study included 24 patients with malignant ovarian neoplasia treated at the Pelvic Mass Outpatient Clinic of the Clinical Hospital of the Federal University of Triângulo Mineiro. The neutrophil/lymphocyte ratio was calculated as the absolute number of neutrophils divided by the absolute number of lymphocytes. Expression of the cytokines was evaluated by the immunohistochemistry method (IL2, IL5, IL6, IL8, IL10 and TNF-R1). Fisher's statistical test was used for the comparisons of immunohistochemical expression with the neutrophil/lymphocyte ratio, and the unpaired T-Test was used in the analysis of the association of this ratio with tumor staging. RESULTS: A neutrophil/lymphocyte ratio > 2.6 was significantly higher in the more advanced stages (II-IV) of malignant ovarian neoplasia (p = 0.0098). In addition, this ratio > 2.6 was associated with IL2 stromal immunostaining (1-3) (p = 0.0472). CONCLUSION: Stromal IL-2 is associated with higher a neutrophil/lymphocyte ratio, suggesting a worse prognosis in ovarian cancer and its role in tumor immunology; a neutrophil/lymphocyte ratio > 2.6 is associated with more advanced stages of malignant ovarian neoplasia.

Increased flexibility, pain reduction and unaltered levels of IL-10 and CD11b + lymphocytes in patients with systemic lupus erythematosus were associated with kinesiotherapy.

The effect of physical activity on the immune system is still poorly understood in cases of systemic lupus erythematosus (SLE). Therefore, our aim was to investigate differences in the serum levels of cytokines (IL-2, IL-5, IL-6, IL-8, IL-10 and TNF-α) and the numbers of CD11b + and CXCR2 + neutrophils and lymphocytes in women with SLE undergoing drug treatment, without ( n = 9) or with ( n = 5) 4 months of kinesiotherapy. Parameters related to functional capacity were also analyzed. In the case of the patients who were not submitted to kinesiotherapy, there were reductions in the levels of IL-5, IL-6 and IL-10, and an increase in the number of CD11b + leukocytes, in addition to an increase in abdominal circumference after the monitoring time. Patients submitted to kinesiotherapy did not present changes in serum cytokines or in the numbers of CD11b + and CXCR2 + neutrophils and lymphocytes, but there were increases of flexibility and strength, as well as a reduction in pain sensation after the monitoring time. In conclusion, kinesiotherapy was able to increase flexibility and reduce pain in SLE patients without influencing immune parameters.

Role of Intracystic Cytokines and Nitric Oxide in Ovarian Neoplasms.

The development of new biomarkers for the diagnosis and prognosis of ovarian cancer may provide an opportunity for new therapies. In this study, we aimed to compare cytokines (interleukin [IL]-2, IL-5, IL-6, IL-8, IL-10 and tumour necrosis factor [TNF]-α) and nitric oxide (NO) metabolite levels in non-neoplastic tumours, benign primary ovarian tumours and malignant primary ovarian neoplasms. The secondary aim was to relate cytokine and intracystic NO metabolite levels to clinical, laboratory and pathologic characteristics for patients with primary ovarian malignancies. We evaluated 110 patients with adnexal masses. Cytokine concentrations were quantified by enzyme-linked immunosorbent assay and nitrate concentrations by enzymatic reduction of nitrite by nitrate reductase. Patients with malignant neoplasms had higher IL-6, IL-8 and NO levels compared to patients with benign neoplasms. Histologic grade 1 tumours were associated with elevated IL-2 levels, whereas anaemia was associated with elevated IL-6 levels. On average, those patients with elevated IL-8 levels also had a neutrophil/lymphocyte ratio (NLR) greater than 2.6 and less than 36 months of disease-free survival (DFS). Patients with normal CA 19-9 levels had elevated IL-10 levels. TNF-α was elevated in patients with two carcinogenesis and those with a platelet/lymphocyte ratio (PLR) less than 300. NO levels were higher in patients with an NLR less than 2.6 and CA 19-9 greater than 35 U/ml. Elevated intracystic cytokine levels, especially IL-6 and IL-8, are associated with worse prognosis in ovarian cancer.

Placental and umbilical cord macroscopic changes associated with fetal and maternal events in the hypertensive disorders of pregnancy.

AIM: The purpose of this study was to identify placental and umbilical cord macroscopic changes and correlate them to maternal and fetal clinical events in hypertensive disorders of pregnancy (HDP). MATERIALS AND METHODS: The authors examined 150 placentas, 30 from each HDP group, totaling 120, and 30 from the control group. All placentas and umbilical cords were examined, recorded, and photographed. RESULTS: The mean placental weight in the control group (526.3 +/- 95.6 g) was greater than in the HDP (435.5 +/- 43.1 g). Calciphylaxis was the most common macroscopic change found in the control and HDP groups in 27 (90%) and 118 cases (98.3%), respectively. DISCUSSION: Pregnant women with HDP were relatively younger. In addition, due to low blood flow seen in HDP, the macroscopic changes found included lower placental weight, calciphylaxis in the maternal surface, and fibrin in the fetal surface. Because of all complications associated, most women with HDP had preterm infants who developed respiratory problems and had shorter umbilical cords.

Frequency of endometriosis and adenomyosis in patients with leiomyomas, gynecologic premalignant, and malignant neoplasias.

OBJECTIVE: This study investigated the association between gynecological neoplasms, endometriosis, and adenomyosis in women who underwent surgical treatment for gynecological cancer and uterine leiomyoma during reproductive years or after menopause. MATERIALS AND METHODS: Information was collected from patient records from the Hospital's database from 1985 to 2007. The study included 502 women, of which 375 were premenopausal and 132 were postmenopausal. RESULTS: A significant association was observed between the occurrence of adenomyosis in cancer in women with four or more pregnancies, and in women aged over 40 years (p < 0.0001). The frequency of adenomyosis was significantly higher than the frequency of endometriosis for cancer in two sites (p = 0.0419) or for leiomyomas (p < 0.0001). CONCLUSION: Therefore adenomyosis is more frequently found than endometriosis in women with leiomyomas or cancer in two sites in premenopausal women, and clinicians need to be aware of patients with adenomyosis and the risk of cancer.

IL-17 and IL-22 serum cytokine levels in patients with squamous intraepithelial lesion and invasive cervical carcinoma.

PURPOSE: Several works correlate the synthesis of IL-17 and IL-22 with tumoral progression. However, there are no studies of these cytokines on cervical cancer. The authors studied the concentration of IL-17 and IL-22 on serum obtained from patients with different grades of squamous intraepithelial lesions (SILs) and invasive cervical carcinoma. MATERIALS AND METHODS: Eighty-one women were enrolled in this study, including 23 in the healthy control (with no history of infection or lesions), 11 with low-grade squamous intraepithelial lesion (LSIL), 36 with high-grade squamous intraepithelial lesion (HSIL), and 11 who were diagnosed anatomo-pathologically with invasive carcinoma. Levels of the IL-17 and IL-22 cytokines were measured in the serum obtained from these patients using the enzyme-linked immunoabsorbent assay (ELISA) method. RESULTS: IL-17 and IL-22 displayed a similar pattern of results, with an increase in the serum level of LSIL patients, when compared with serum from HSIL patients (respectively, mean- pg/ml: 22.50 vs 12.20, and 168.2 vs 61.48, p < 0.05). CONCLUSION: Concentrations of IL-17 and IL-22 in the peripheral blood of patients with LSIL were increased compared to HSIL patients.

Frequency of recurrence after surgical treatment of cervical intraepithelial neoplasia grade 1-3.

PURPOSE OF INVESTIGATION: The objective was to demonstrate the frequency of invasive cervical cancer or recurrent CIN in patients treated by a previous diagnosis of CIN 1-3. METHODS: We analyzed 1,397 records colpocytologic and medical records. Recurrence of CIN or invasive neoplasia of the cervix after treatment of CIN was assessed. The chi-square test was used for statistical analysis (significance level set at less than 0.05). RESULTS: We obtained 696 CIN 1, 244 CIN 2, 451 CIN 3, and six squamous carcinoma. Regarding patients who relapsed, there were 6/690 (0.9%) patients had an initial diagnosis of CIN 1, 8/236 (3.4%) CIN 2 and 21/430 (4.9%) CIN 3 (p < 0.0001). Comparing the frequency of relapse among each group, we found: CIN 1 vs CIN 2: p = 0.0073; CIN 1 vs CIN 3: p < 0.0001; CIN 2 vs CIN 3: p = 0.38. CONCLUSION: Although the number of relapses when comparing CIN 2 and CIN 3 were not significant, the data suggest that CIN 2 has lower recurrence rates, so these patients require more conservative treatment if a desire of future pregnancy is expressed.

Immune response and immunotherapy in intraepithelial and invasive lesions of the uterine cervix.

Infection with the human papillomavirus virus (HPV) induces innate and acquired immune responses in the cervical stroma, which are a delicate, balanced and generally unpredictable immunological defense. Because of the immunological breaks that the HPV virus causes, eradication of infected cells does not occur, potentially leading to development of intraepithelial and invasive lesions. Advances in our understanding of the immune system and in the definition of antigens in tumor cells has led to many new treatment strategies. As a result, immunotherapy has the potential to be the most specific treatment for tumors, and one that requires elaboration. Recently, immunotherapy with interferon and dendritc cells has been used on intrapepithelial and invasive cervical lesions with promising results.

Immunotherapy with dendritic cells for gynecological neoplasias: a new therapeutic approach?

The immune system consists of a complex collection of mediators and cells that act in a coordinated way to eliminate neoplastic cells. One of immunotherapy's promises is the development of cellular vaccines, or more specifically, vaccines with dendritic cells. However, we still have a lot left to study and learn, since we already know that patients with tumors of the same histological grade can have completely different behaviors when given the same immunological stimulus. We believe that antitumor immunotherapy will lead to a personalized vaccine, since the scheme of treatment, the stimuli and the dosages need to be tailored to each patient.

Myofibroblastic inflammatory breast tumor and fibrosarcoma: a case report.

Myofibroblastic inflammatory tumors can occur in any human tissue. They are benign lesions and more common in young patients. We describe the case of a 41-year-old patient with a nodule measuring 2.5 x 1.5 cm in the superior lateral quadrant of the left breast. The pathological examination showed proliferation of the spindle cells in dense fascicles interspersed by colagen among frequent plasmocytes, lymphocytes and eosinophils, associated with scarce typical mitosis. In the same site ten years before the patient had undergone a nodulectomy and the diagnosis was a benign filloid tumor. The patient returned with a nodule in the surgical scar at follow-up and the incisional biopsy showed a malignant filloid tumor with a sarcomatous component. A mastectomy was performed.

Immunological evaluation of vaginal secretion in patients with high-grade cervical intraepithelial neoplasia treated with intralesional interferon alpha-2b.

INTRODUCTION: Conservative treatment with intralesional interferon (IFN) is a therapeutic option for cervical intraepithelial neoplasia (CIN) patients of childbearing age. MATERIALS AND METHODS: The study group was made up of patients diagnosed with a high-grade lesion and treated with intralesional human recombinant IFNalpha-2b. Vaginal secretion was collected during IFNalpha-2b treatment for analysis of cytokines and viral load. RESULTS: The initial histology diagnostic was 62.5% (n = 5) with CIN 2 and 37.5% (n = 3) with CIN 3. In terms of clinical evaluation and anatomopathology, 6.5% (n = 5) had a good clinical response, while 37.5% (n = 3) had therapeutic failure. All the patients with therapeutic failure were smokers. Interleukin 6 and tumor necrosis factor-alpha concentrations were raised at the sixth application for the patient group who failed to respond to therapy compared to the responsive group (p = 0.0357). Patients with a good response exhibited a reduction in human papillomavirus viral load (p = 0.03). CONCLUSIONS: Patients that had a good response had lower concentrations of inflammatory cytokines than did non-responders.

Expression of cytokines in cervical stroma in patients with high-grade cervical intraepithelial neoplasia after treatment with intralesional interferon alpha-2b.

Conservative treatment with interferons (IFNs) has the advantage of preserving reproductive capacity in patients with grade 2 or 3 cervical intraepithelial neoplasia (CIN). The objective of this work was to study patients with high-grade CIN treated with intralesional IFN alpha-2b and to analyze the expression of Th1, Th2 and Th3 cytokines in cervical stroma. We observed that patients with a satisfactory response (60%) to treatment with IFN alpha-2b expressed more Th1 (IFN-gamma TNF-alpha, IL-2) cytokines, with a significant reduction in the viral load of high-risk human papillomavirus (p = 0.0313). All patients with therapeutic failure were smokers and had higher expression of cytokines Th2 (IL-4) or Th3 (TGF-beta2 and TGF-beta3).

The clinical use of type 1 interferon in gynecology.

Interferons were initially described in terms of their role in blocking viral replication. They are important cytokines that act on various aspects of cell physiology. Importantly, they can affect cell proliferation or induce the differentiation of neoplastic cells. The exact way in which the interferon complex (IFN) acts on tumours is still unknown, although their use in clinical practice has been widely recommended, especially with tumours that are resistant to conventional treatments, or in situations where surgical removal might lead to a loss of organ function. IFN can be employed as a treatment for various chronic diseases, including tumours. Indeed interferon cytokines are the therapy of choice in certain situations. However, one of the difficulties yet to be overcome is the need for frequent administrations of the drug. We believe that the development of new formulations is needed to match the demand for its use in oncology treatment.

Analysis of the cytogenetic response in peripheral blood lymphocytes from breast cancer patients following chemotherapy.

The presence of chromosomal aberrations induced in circulating lymphocytes from breast cancer patients during chemotherapy was analyzed. Ten breast cancer patients undergoing neoadjuvant chemotherapy and ten healthy women (controls) were evaluated. Metaphases were obtained from cultures of peripheral lymphocytes stimulated with phytohemaglutinin and metaphase blockage was achieved with colchicine. One hundred metaphases were analyzed for chromosomal aberrations and 1,000 cells for the mitotic index. No significant differences were observed regarding the frequency of chromosomal aberrations, number of cells with chromosomal aberrations and mitotic index between the controls and patients before chemotherapy. However, after the first chemotherapy cycle, the numbers of chromosomal aberrations and cells with them was greater. After the third cycle, the mitotic index was lower, but the fifth cycle produced an increase in relation to the third and fourth cycles. The results suggest that chemotherapy raises the number of chromosomal aberrations and favors persistence of stable chromosomal abnormalities.

Gynecological malignant neoplasias diagnosed after hysterectomy performed for leiomyoma in a university hospital.

PURPOSE: To analyze the findings of malignant neoplasms after hysterectomy for benign conditions. METHODS: A retrospective study from January 1987 to December 2008 was conducted. We analyzed all simple hysterectomies with or without salpingo-oophorectomy for benign conditions (leiomyoma). Incomplete dossiers of patients or cases with uncertain clinical diagnostics were excluded. We analyzed histopathological results, age, parity, indications for hysterectomies with or without salpingo-oophorectomy, stage (if malignant) and therapy. RESULTS: 2,016 hysterectomies with or without salpingo-oophorectomy were performed. Of 2,016, 652 (32.3%) had had a previous diagnosis of malignancy and 1,364 (67.7%) had had a clinical diagnosis of benignancy (leiomyoma). From the total of 1,364, three (0.22%) cases of cancer were diagnosed after anatomopathological study of the uterine specimen, two sarcomas and one endometrial cancer. No cases of incidental ovarian or uterine cervical cancer were diagnosed. CONCLUSIONS: Gynecological malignances in surgical specimens of patients submitted to surgery (hysterectomy and/or salpingo-oophorectomy) for benign conditions are rarely found.

Pregnancy outcome after treatment of cervical intraepithelial neoplasia by the loop electrosurgical excision procedure and cold knife conization.

PURPOSE OF INVESTIGATION: The aim of this study was to evaluate the effect of LEEP and cold-knife conization on the outcome of subsequent pregnancy in a tertiary public hospital. METHODS: One hundred and ninety-nine patients met the inclusion criteria (age between 18 and 45 years old). Cold-knife conization, LEEP, and both (conization and LEEP) were performed in 102 (51.3%), 95 (47.7%) and two (1%) women, respectively. Average ages were respectively, 33 +/- 7.3; 25 +/- 6.73 and 30 +/- 2.8. RESULTS: Pregnancies occurred 2.6 and 4.8 years after LEEP and conization, respectively. Miscarriages and preterm pregnancies were more frequent in conization cases versus LEEP, 26% and 5.2%, 23% and 5.5%, respectively. CONCLUSION: If patients express a desire for pregnancy, LEEP should be the procedure of choice.