Cu isotope ratios are meaningful in ovarian cancer diagnosis.

BACKGROUND: Ovarian cancer diagnosis is currently based on imaging and circulating CA-125 concentrations with well-known limits to sensitivity and specificity. New biomarkers are required to complement CA-125 testing to increase effectiveness. Increases in sensitivity of isotopic separation via multi collector inductively coupled plasma-mass spectrometry have recently allowed highly accurate measurement of copper (Cu) isotopic variations. Studies in breast cancer patients have revealed changes of serum copper isotopic composition demonstrating the potential for development as a cancer biomarker. Evaluating 65Cu/63Cu ratios (δ65Cu) in serum samples from cancer patients has revealed a strong correlation with cancer development. In this study blood samples from forty-four ovarian cancer patients, and 13 ovarian biopsies were investigated. RESULTS: Here we demonstrate that changes in Cu isotopes also occurs in ovarian cancer patients. Copper composition determined by multiple collector inductively coupled plasma mass spectrometry revealed that the copper isotopic ratio δ65Cu in the plasma of 44 ovarian cancer patient cohort was significantly lower than in a group of 48 healthy donors, and indicated that serum was enriched for 63Cu. Further analysis revealed that the isotopic composition of tumour biopsies was enriched for 65Cu compared with adjacent healthy ovarian tissues. CONCLUSIONS: We propose that these changes are due to increase lactate and Cu transporter activities in the tumour. These observations demonstrate that, combined with existing strategies, δ65Cu could be developed for use in ovarian cancer early detection.

The predictive role of thrombocytosis in benign, borderline and malignant ovarian tumors.

Ovarian cancer is a lethal gynecological malignancy. Although CA-125 is commonly measured in women with adnexal mass, it is estimated that it only has a positive predictive value (PPV) of 69% and a negative predictive value (NPV) of 88% for the detection of ovarian cancer. The aim of this study was to investigate the diagnostic significance and predictive impact of thrombocytosis in women with suspected or confirmed ovarian cancer. This was a retrospective study of women who had surgery for adnexal mass over a 48-month period between September 2014 and September 2018 at Swansea Gynecological Oncology Center in Wales, UK. A total of 294 women who underwent surgery for high-risk pelvic mass or biopsy-confirmed ovarian cancer were identified. 206 women (70%) had final histology confirming ovarian cancer, 54 women (18%) had benign tumors while 34 women (12%) had borderline tumors. 90/206 women (43.7%) with ovarian cancer had thrombocytosis prior to primary surgery or neoadjuvant chemotherapy compared to 8/54 (14.8%) for benign tumors and 4/34 (11.8%) for borderline tumors. Thrombocytosis was observed in 23.2%, 40%, 45.1%, and 65.1% of Stages I, II, III, and IV ovarian cancer, respectively. Thrombocytosis was a stronger predictor of ovarian malignancy in younger women of less than 60 years (p = .041). Overall, the positive likelihood ratio of platelet count in the detection of ovarian cancer was 2.61 while the negative likelihood ratio was 0.72, with a diagnostic odds ratio of 3.625. Thrombocytosis was strongly associated with advanced stage ovarian cancer (Stage III/IV) (p = .002). Interestingly, 4/8 (50%) women with thrombocytosis in the benign ovarian tumor group were diagnosed with ovarian fibroma/fibrothecoma, which often mimics advanced ovarian cancer at presentation. Predictive markers for borderline tumors continue to remain a challenge. We believe that there is a role for platelet count in primary care algorithm for women with suspected ovarian cancer. We suspect that platelets play a role in the metastasis of ovarian cancer.

Efficacy of 5% imiquimod for the treatment of Vaginal intraepithelial neoplasia-A systematic review of the literature and a meta-analysis.

Vaginal intraepithelial neoplasia (VaIN) is an uncommon disease associated with HPV and is considered to be a precursor of vaginal carcinoma. To date, treatment recommendations vary with no universally accepted standard of care as best treatment modality. Nevertheless, 5% imiquimod appears to be a promising, alternative, non-invasive treatment option. To ascertain the efficacy of 5% imiquimod for the treatment of this rare condition, we conducted a systematic review and meta-analysis of the proportion of women who received 5% imiquimod with their complete response, HPV clearance and recurrence rates. A literature search was carried out throughout the PubMed, EMBASE, ClinicalTrials.gov and Cochrane Databases for relevant studies. We computed the summary proportions for complete response, HPV clearance and non-recurrence following administration of 5% imiquimod by random effects meta-analysis. Six articles reporting on 94 patients were included. The summary proportions of women with complete response and HPV clearance were 76.5% (95% CI 59.4-98.5) and 52.5% (95% CI 29.5-93.6) respectively. The summary proportion of women with non-recurrence appeared high (94.3% (95% CI 67.1-132)), yet not significant. Use of 5% imiquimod for the treatment of VaIN is associated with relatively high response rate, satisfactory HPV clearance, whilst the risk for VaIN recurrence appears low.

Management of advanced ovarian cancer in South West Wales - a comparison between primary debulking surgery and primary chemotherapy treatment strategies in an unselected, consecutive patient cohort.

OBJECTIVES: This study represents the first reported outcomes for patients with advanced ovarian cancer (AOC) in South-West Wales undergoing treatment with primary debulking surgery or primary chemotherapy respectively. METHODS: This is a retrospective study of consecutive, unselected patients with advanced ovarian, fallopian tube or primary peritoneal cancer (FIGO III/IV) presenting to a regional cancer centre between October 2007 and October 2014. Patients were identified from Welsh Cancer Services records and relevant data was extracted from electronic National Health Service (NHS) databases. Main outcome measures were median overall survival (OS), progression free survival (PFS) and perioperative adverse events. Hazard ratio estimation was carried out with Cox Regression analysis and survival determined by Kaplan-Meier plots. RESULTS: Of 220 women with AOC, 32.3% underwent primary debulking surgery (PDS) and 67.7% primary chemotherapy and interval debulking (PCT-IDS). Patients were often elderly (median age 67 years) with a poor performance status (26.5% PS >1). Complete cytoreduction (0cm residual) was achieved in 32.4% of patients in the PDS group and in 50.0% of patients undergoing IDS. Median OS for all patients was 21.9 months (PDS: 27.0 and PCT-IDS: 19.2 months; p >0.05) and median PFS was 13.1 months (PDS: 14.3 months and PCT-IDS: 13.0 months; p >0.05). Median overall and progression free survival for patients achieving complete cytoreduction were 48.0 and 23.2 months respectively in the PDS group and 35.4 months and 18.6 months in the IDS group (p >0.05). CONCLUSION: This retrospective study of an unselected, consecutive cohort of women with AOC in South West Wales shows comparable survival outcomes with recently published trials, despite the relatively advanced age and poor performance status of our patient cohort. Over the seven-year study period, our data also demonstrated a non-significant trend towards improved survival following primary surgery in patients who achieved maximal cytoreduction. Our future aim therefore is to examine and develop the role of extended surgery in these patients.

Simplified staging laparotomy in FIGO stage 1 epithelial ovarian cancer: follow-up and outcomes in south Wales, U.K.

We have conducted a retrospective analysis of FIGO stage 1 ovarian cancer patients in south Wales, who underwent a simplified staging laparotomy without routine nodal sampling and peritoneal biopsies. Patient records from January 2004 to December 2010 were analysed. A total of 116 patients were included in the final analysis. Adjuvant chemotherapy was offered to patients with risk factors for relapse (grade > 1, clear cell histology, or stage > Ia); overall, 89 patients (76.7%) received adjuvant single agent carboplatin (n = 54, 46.5%) or combination chemotherapy (n = 35, 30.2%). After a median follow up of 41 months (range 12-95), 18 patients have relapsed (15.5%), of these 17 had risk factors and 16 had received adjuvant chemotherapy. Eighteen patients have died, of whom 6 of non-cancer related causes without prior relapse. 5-year overall and relapse free survival were 80%. In conclusion, in situations where there are limited resources and operating time constraints, our data suggest that a simplified staging laparotomy approach may be a reasonable compromise in apparently early stage ovarian cancer: this may result in a more aggressive use of chemotherapy, but survival outcomes seem comparable to other series.

Predictors of ovarian reserve in young women with breast cancer.

Ovarian reserve can be diminished following treatment for breast cancer. This study evaluated biochemical and biophysical parameters of ovarian reserve in these patients. Biochemical and biophysical tests of ovarian reserve were performed simultaneously in young (age 22-42 years), regularly menstruating women with breast cancer (n=22) and age-matched controls (n=24). All tests were performed before (baseline) and after transient ovarian stimulation in the early follicular phase. Patients were recruited both before and after completion of chemotherapy, with some patients being followed up prospectively. Serum samples were analysed for follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol (E(2)), inhibins A and B, and antimullerian hormone (AMH). Biophysical (ultrasound) tests included ovarian volume, antral follicle count (AFC), ovarian stromal blood flow and uterine dimensions. Significant differences were revealed (when compared with the controls) for basal FSH (11.32+/-1.48 vs 6.62+/-0.42 mIU ml(-1), P<0.001), basal AMH (0.95+/-0.34 vs 7.89+/-1.62 ng ml(-1), P<0.001) and basal inhibin B (19.24+/-4.56 vs 83.61+/-13.45 pg ml(-1), P<0.001). Following transient ovarian stimulation, there were significant differences in the increment change (Delta) for inhibin B (3.02+/-2.3 vs 96.82+/-16.38 pg ml(-1), P<0.001) and E(2) (107.8+/-23.95 vs 283.2+/-40.34 pg ml(-1), P<0.01). AFC was the only biophysical parameter that was significantly different between patients and the controls (7.80+/-0.85 vs 16.77+/-1.11, P<0.001). Basal and stimulated biochemical (serum AMH, FSH, inhibin B and E(2)) and biophysical (AFC) tests may be potential markers of ovarian reserve in young women with breast cancer.

Pregnant women in Trinidad have low plasma triacylglycerol and small babies

OBJECTIVE: To determine plasma lipid concentrations in non-pregnant women, pregnant women, and their infants. DESIGN AND METHODS: A cross-sectional study of non-pregnant and pregnant African-Trinidadian (AT) and Indian-Trinidadian (IT) women was carried out at Mount Hope Hospital, Trinidad. Adult and cord blood samples were collected and birth weights recorded. Plasma triacylglycerol (TAG), phosphatidylcholine (PC) and non-esterified fatty acid concentrations were determined by gas chromatographic analysis. RESULTS: On average, infants born to both AT (n=4) and IT (n=5) women were of lower birthweight than reference standards; medians 3.07 (2.7-4.6) kg and 3.22 (2.58-4.02) kg, respectively. Plasma lipid concentrations in non-pregnant and pregnant women, and umbilical cord were similar for AT and IT women. Plasma concentrations of PC and nonesterified fatty acids (NEFA) were not significantly different between non-pregnant and pregnant women. Median plasma TAG concentration was significantly (p<0.05) greater at term 1.8 (0.6-2.0) mmol/l for AT (n=7); 1.9 (1.5-2.7) mmol/l for IT (n=5) compared with non-pregnant women 0.8 (0.5-1.3) mmol/l for AC; 1.0 (0.5-1.7 mmol/l for EI) n=5/group. Term TAG concentrations were markedly lower than reported previously for Caucasian (2.76 mmol/l). Indian (2.76 mmol/l) and Nigerian (2.7-2.9 mmol/l) women, while values in non-pregnant and pregnant women at 20-22 weeks and 30-34 weeks were comparable. CONCLUSIONS: Since maternal hyperlipidaemia in pregnancy may serve to increase supply of lipids to the foetus during the principal growth phase, low maternal TAG concentrations in late gestation may have contributed to the lower birth weight of these infants. Low birth weight is associated with an increased risk of cardiovascular disease and type 2 diabetes in adults. Therefore, low maternal plasma TAG leading to poor foetal weight gain and impaired growth may represent one potential mechanism which contributes to the high prevalence of heart disease and diabetes in the population of Trinidad.(Au)

Effect of pregnancy on plasma lipid concentration in Trinidadian women. Result of a pilot study

In Trinidad and Tobago, Cardiovascular disease and Type 2 diabetes mellitus are important causes of morbidity and mortality, and birth weight is significantly less than reference standards. Lower birth weight is associated with increased risk of these diseases. Variation in birth weight is due, in part, to deposition of adipose tissue in the foetus during the last trimester at the same time that maternal plasma triacylglycerol (TAG) increases. We conducted a pilot cross-sectional analysis of maternal plasma lipid status and birth weight in healthy, non-pregnant, primigravida Trinidadian women. Non-pregnant and pregnant women, in their second and third trimesters, and at term, were recruited at random from an antenatal clinic. Adult and umbilical cord plasma TAG, non-esterified fatty acids (NEFA) and phosphatidylcholine (PC) concentrations were determined from gas chromatographic analysis of fatty acids. Maternal height, weight, skinfold thickness and infant birth weight were measured. The infant born to Afro-Trinidadian and Indo-Trinidadian women were of low to normal birth weight (medians 3.07 and 3.22 kg, respectively). At term, plasma TAG concentration was approximately two fold (p <0.05) greater than for non-pregnant women. The increment between 30-34 weeks was 1.5 to 1.9 fold lower than reported in other populations. There was a strong relationship (r=0.8771, p=0.019) between maternal and cord plasma TAG and NEFA, but not PC concentrations. There was no significant relationship between maternal TAG concentration at term and birth weight. The result suggests an impaired ability to increase plasma TAG concentration during late gestation. (AU)