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.

Management of neonatal ovarian cysts and its effect on ovarian preservation.

BACKGROUND/PURPOSE: Management of asymptomatic neonatal ovarian cysts varies. Some surgeons advocate initial observation, while others recommend immediate operation depending on cyst size and complexity. This study aims to compare outcomes of initial observation versus primary surgery, focusing on incidence of postnatal torsion and ovarian preservation. METHODS: A retrospective study (1997-2012) of neonates with an ovarian mass was performed. Data on cyst size, ultrasound characteristics, clinical course, complications, and pathology were extracted. RESULTS: Thirty-seven neonates with asymptomatic ovarian cysts were identified (N=25 observed, N=12 primary surgery). Overall, 12/25 (48%) observed had successful cyst regression, including 3/8 (38%) cysts ≥50mm and 6/15 (40%) complex. 13/25 patients (52%) underwent surgery for failure of cyst regression (11/13) or concern for interval torsion (2/13). Postnatal torsion occurred in 1/25 observation patients (4%), or 1/8 (13%) with cysts≥50mm. Overall rate of ovarian preservation between groups was not statistically different [6/8 (75%) observed versus 8/9 (89%) primary surgery; P=0.577]. Pathology found viable ovarian tissue in all oophorectomy specimens (N=3). CONCLUSIONS: Postnatal torsion is rare. A period of observation spares half of neonates from an operation, without decreasing ovarian salvage. Initial management should consist of observation, regardless of size or complex characteristics. If operative intervention is necessary, ovary preserving techniques should be utilized.

Adnexal torsion leading to death of an infant.

BACKGROUND: Torsion of the uterine adnexa is an uncommon occurrence in infants, but when it does occur, the consequences may be catastrophic. CASE: A 4-month-old female presented with sudden cardiac and respiratory arrest. There were no prior signs of illness. The infant was resuscitated and survived for one day after the event. Autopsy revealed a left ovarian cyst with torsion. Necrosis of the transverse colon was also seen. Other organs revealed signs of shock. The cause of death was felt to be related to the torsion. SUMMARY AND CONCLUSION: Torsion of the uterine adnexa is rare in infants. In the few reported cases, antecedent symptoms were present. Clinicians should be aware of this possibility and include it in the differential diagnosis of death in infancy.

Benign ovarian cysts and ovarian cancer: a cohort study with implications for screening.

BACKGROUND: Whether some benign ovarian cysts can develop into cancerous cysts is not known. If a large proportion of ovarian cancers arose in this way, it might be possible to remove the benign cysts in a screening programme before they became malignant. We used follow-up data from a cohort of 5479 self-referred women without symptoms, who participated in a ultrasonographic-screening trial for early ovarian cancer between June, 1981, and August, 1987. We assessed whether the removal of persistent ovarian cysts from these women was associated with a reduction in the expected number of deaths from ovarian cancer in the cohort as a whole. METHODS: The expected number of deaths from all causes, all cancers, and ovarian, breast, and colorectal cancers were calculated for the study cohort by the standard life-table method. The actual number of deaths and each cause were obtained and the proportional mortality ratio was calculated for each cause of death. FINDINGS: 5135 (95%) of the participants in the original trial were traced. During the screening, five of these women were found to have stage I epithelial ovarian cancer and 88 had benign epithelial ovarian tumours. The number of reported deaths from all causes (387 [50% of expected]), all cancers (221 [71%]), and ovarian cancer (22 [90%]) was lower than expected because of the "healthy-volunteer effect". Proportional mortality ratios were 100% (by definition) for all cancers, 141% for breast cancer, 128% for ovarian cancer (95% CI 87.7-187.6, p=0.19), 84% for colorectal cancer, and 48% for lung cancer. INTERPRETATION: The removal of persistent ovarian cysts was not associated with a decrease in the proportion of expected deaths from ovarian cancer relative to other cancers during follow-up. For population-based screening of healthy women without a family history of ovarian cancer, a screening test is required that is specific and sensitive to early malignant disease, and inexpensive.

Prognostic relevance of soluble interleukin-2 receptors in patients with ovarian tumors.

Soluble interleukin-2 receptors (sIL-2R) are measurable in the sera of patients with ovarian cancer and several other benign and malignant diseases. However, the function of these sIL-2R is still unclear. Since high levels of sIL-2R are thought to be an indicator of an activated immune system we investigated the correlation of sIL-2R concentration and prognosis of ovarian cancer patients. sIL-2R measurement was performed on the preoperative sera of 130 patients with benign, and 119 patients with malignant ovarian tumors. The IMMULITE sIL-2R assay by DPC Biermann, Bad Nauheim, Germany was used. In ovarian cancer patients sIL-2R concentrations were significantly higher than in those with benign tumors. By defining the 95th percentile of the sIL-2R concentration distribution in patients with benign diseases as the cut-off (1200 U/ml) 35% of the ovarian cancer patients had elevated concentrations. Concentrations of sIL-2R increased with FIGO stage. FIGO-III patients with highly elevated sIL-2R concentrations tended to have better prognosis than those with sIL-2R levels within normal range in contrast to FIGO IV patients. Since sIL-2R concentrations indicate an immunological activation in ovarian cancer patients our data give hints of the possible role of sIL-2R in the assessment of the risk of recurrence in ovarian cancer patients.

Expression of ras oncogene p21 protein in normal and neoplastic ovarian tissues: correlation with histopathologic features and receptors for estrogen, progesterone, and epidermal growth factor.

OBJECTIVE: The aim of the study was to investigate the biologic significance of p21 expression in normal and neoplastic ovarian tissues. STUDY DESIGN: Western blotting analysis of p21/ras oncoprotein was conducted in a group of 14 normal and cystic ovaries, six benign tumors, 42 primary ovarian cancers, and 15 omental metastases. RESULTS: Levels of p21 were similar in normal and cystic ovaries and in benign tumors, whereas they were significantly higher in malignant tumors than in control tissues (median 1.91, range 0.12 to 5.00 vs median 1.03, range 0.32 to 2.20; p = 0.023) and in omental metastases than in primary ovarian carcinomas (median 3.05, range 0.55 to 5.72 vs median 1.97, range 0.12 to 5.00; p = 0.14). We found no correlation between p21 expression and histopathologic or clinical characteristics. Estrogen receptor-positive and progesterone receptor-positive tumors expressed higher p21 levels than did estrogen receptor-negative and progesterone receptor-negative tumors (p < 0.05), but no correlation with epidermal growth factor receptor status was found. In the univariate analysis of survival p21 positivity showed a negative prognostic value. CONCLUSION: The enhancement of p21 protein is associated in the ovarian tissue with the malignant phenotype and the acquisition of metastatic potential.