Showing papers by "Donal J. Brennan published in 2015"

Serum HE4 detects recurrent endometrial cancer in patients undergoing routine clinical surveillance

Abstract: The purpose of this study was to evaluate serum HE4 as a biomarker to detect recurrent disease during follow-up of patients with endometrial adenocarcinoma (EAC). We performed a retrospective analysis of 98 EAC patients treated at Innsbruck Medical University, between 1999 and 2009. Twenty-six patients developed recurrent disease. Median follow-up was 5 years. Serum HE4 and CA125 levels were analyzed using the ARCHITECT assay (Abbott, Wiesbaden, Germany) pre-operatively (baseline), post-operative (interval) and after histological confirmation of recurrent disease or when patients returned for clinical review with no evidence of recurrent disease (recurrence/final)). Receiver operator curves (ROC), Spearman rank correlation coefficient, chi-squared and Mann–Whitney tests were used for statistical analysis. HE4 levels decreased after initial treatment (p = 0.001) and increased again at recurrence (p = 0.002). HE4 was elevated (>70 pmol/L) in 21 of 26 (81%) and CA125 was elevated (>35 U/ml) in 12 of 26 (46%) patients at recurrence. In endometrioid histology (n = 69) serum HE4 measured during follow up (Area under the curve (AUC) = 0.87, 95%CI 0.79-0.95) was a better indicator of recurrence than CA125 (AUC = 0.67, 95%CI 0.52-0.83). A HE4 level of 70 pmol/L was associated with a sensitivity of 84%, a specificity of 74% and a negative predictive value of 93% when assessing for recurrent endometrioid EAC. This is a preliminary description of HE4 serum levels measured during routine follow up of EAC patients. Serum HE4 measured during clinical follow-up may identify recurrent disease particularly in patients with endometrioid histology. Further prospective validation of HE4 is warranted.

Surgical management of abnormally invasive placenta: a retrospective cohort study demonstrating the benefits of a standardized operative approach.

Abstract: Introduction. Abnormally invasive placenta is a major cause of maternal morbidity and mortality. The aim of this study was to assess the effectiveness of a standardized operative approach performed by gynecological oncologists in the surgical management of abnormally invasive placenta. Materials and methods. We performed a retrospective analysis of all cases of morbid placental adherence managed at the Mater Mothers' Hospitals, Brisbane, Australia between January 2000 and June 2013. A standard operative approach involving extensive retro-peritoneal and bladder dissection before delivery of the fetus, was undertaken when a gynecological oncologist was present at the start of the procedure. Main outcome measures were estimated blood loss, transfusion requirements, and maternal and neonatal morbidity. Results. The study includes 98 cases of histologically confirmed abnormally invasive placenta. Median estimated blood loss for the entire cohort was 2150 mL (range 300-11 500 mL). Women were divided into three groups, (1) those who had a gynecological oncologist present at the start of the procedure (group 1; n = 43), (2) those who had a gynecological oncologist called in during the procedure (group 2; n = 23), and (3) those who had no gynecological oncologist involved (group 3; n = 32). Group 2 had a significantly higher blood loss than the other groups (p = 0.001) (median 4400 mL). Transfusion requirements were higher in groups 2 and 3 compared with group 1 (p = 0.004). Other maternal and neonatal morbidity was similar across all three groups. Conclusion. This study supports the early presence of a gynecological oncologist at delivery when abnormally invasive placenta is suspected and demonstrates that a "call if needed" approach is not acceptable for these complex cases.

Downregulation of the cancer susceptibility protein WRAP53β in epithelial ovarian cancer leads to defective DNA repair and poor clinical outcome.

Abstract: Alterations in the scaffold protein WRAP53β have previously been linked to carcinogenesis and, in particular, associated with an increased risk for epithelial ovarian cancer. Here, we investigated the pathogenic impact and prognostic significance of WRAP53β in connection with epithelial ovarian cancer and examined the underlying mechanisms. We find that reduced expression of WRAP53β in ovarian tumors correlated with attenuated DNA damage response and poor patient survival. Furthermore, in ovarian cancer cell lines, WRAP53β was rapidly recruited to DNA double-strand breaks, where it orchestrated the recruitment of repair factors involved in homologous recombination and non-homologous end joining, including RNF168, 53BP1, BRCA1 and RAD51. Mechanistically, WRAP53β accomplishes this by facilitating the necessary ubiquitinylation at DNA breaks. Finally, we demonstrate that loss of WRAP53β significantly impairs the repair of DNA double-strand breaks, resulting in their accumulation. Our findings establish WRAP53β as a regulator of homologous recombination and non-homologous end joining repair in ovarian cancer cells, suggesting that loss of this protein contributes to the development and/or progression of ovarian tumors. Moreover, our current observations identify the nuclear levels of WRAP53β as a promising biomarker for the survival of patients with ovarian cancer.

Consideration for safe and effective gynaecological laparoscopy in the obese patient

Abstract: Background The number of obese and morbidly obese patients within the developed world is dramatically increasing within the last 20 years. Apart from demographical changes, obese patients are especially prone to have oestrogen-dependent morbidities and neoplasias, of which laparoscopic treatment should be the standard of care. The increasing number of patients with BMI >40 is concerning, making it necessary to summarise considerations for safe and effective Gynaecological Laparoscopic Surgery.