Ann D Fisher

BACKGROUND: This is an update of a previous Cochrane Review published in 2012, Issue 9.Surgery for endometrial cancer (hysterectomy with removal of both fallopian tubes and ovaries) is performed through laparotomy. It has been suggested that the laparoscopic approach is associated with a reduction in operative morbidity. Over the last two decades there has been a steady increase of the use of laparoscopy for endometrial cancer. This review investigated the evidence of benefits and harms of laparoscopic surgery compared with laparotomy for presumed early stage endometrial cancer. OBJECTIVES: To compare overall survival (OS) and disease free survival (DFS) for laparoscopic surgery versus laparotomy in women with presumed early stage endometrial cancer. SEARCH METHODS: For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 5) in the Cochrane Library, MEDLINE via Ovid (April 2012 to June 2018) and Embase via Ovid (April 2012 to June 2018). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. The trial registers included NHMRC Clinical Trials Register, UKCCCR Register of Cancer Trials, Meta-Register and Physician Data Query Protocol. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing laparoscopy and laparotomy for early stage endometrial cancer. DATA COLLECTION AND ANALYSIS: We independently abstracted data and assessed risk of bias. We used hazard ratios (HRs) for OS and recurrence free survival (RFS), risk ratios (RR) for severe adverse events and mean differences (MD) for continuous outcomes in women who received laparoscopy or laparotomy with 9% confidence intervals (CI). These were pooled in random-effects meta-analyses. MAIN RESULTS: We identified one new study in this update of the review. The review contains nine RCTs comparing laparoscopy with laparotomy for the surgical management of early stage endometrial cancer.All nine studies met the inclusion criteria and assessed 4389 women at the end of the studies. Six studies assessing 3993 participants with early stage endometrial cancer found no significant difference in the risk of death between women who underwent laparoscopy and women who underwent laparotomy (HR 1.04, 95% 0.86 to 1.25; moderate-certainty evidence) and five studies assessing 3710 participants found no significant difference in the risk of recurrence between the laparoscopy and laparotomy groups (HR 1.14, 95% CI 0.90 to 1.43; moderate-certainty evidence). There was no significant difference in the rate of perioperative death; women requiring a blood transfusion; and bladder, ureteric, bowel and vascular injury. However, one meta-analysis of three studies found that women in the laparoscopy group lost significantly less blood than women in the laparotomy group (MD -106.82 mL, 95% CI -141.59 to -72.06; low-certainty evidence). A further meta-analysis of two studies, which assessed 3344 women and included one very large trial of over 2500 participants, found that there was no clinical difference in the risk of severe postoperative complications in women in the laparoscopy and laparotomy groups (RR 0.78, 95% CI 0.44 to 1.38). Most studies were at moderate risk of bias. All nine studies reported hospital stay and results showed that on average, laparoscopy was associated with a significantly shorter hospital stay. AUTHORS' CONCLUSIONS: This review found low to moderate-certainty evidence to support the role of laparoscopy for the management of early endometrial cancer. For presumed early stage primary endometrioid adenocarcinoma of the endometrium, laparoscopy is associated with similar OS and DFS. Furthermore, laparoscopy is associated with reduced operative morbidity and hospital stay. There is no significant difference in severe postoperative morbidity between the two modalities.The certainty of evidence for OS and RFS was moderate and was downgraded for unclear risk of bias profiles and imprecision in effect estimates. However, most studies used adequate methods of sequence generation and concealment of allocation so studies were not prone to selection bias. Adverse event outcomes were downgraded for the same reasons and additionally for low event rates and low power thus these outcomes provided low-certainty evidence.

BACKGROUND: Epidemiological and in vitro data implicate androgens in the aetiology of ovarian cancer, but the mechanisms by which this is mediated are unclear. In this study, we wished to examine the effects of androgens on gene expression in ovarian cancer. METHODS: The expression of androgen receptor (AR) in OVCAR3 and OSEC2 cells was confirmed using immunoblotting and response to androgens was measured using flow cytometric assessment of S-phase fraction. The differential gene expression between androgen stimulated and unstimulated OVCAR3 ovarian cancer cells was examined with a cDNA microarray. The upregulation of a subset of these genes was then confirmed with reverse transcriptase PCR in both OVCAR3 and OSEC2, an ovarian epithelial cell line. Finally, the clinical significance of this upregulation was investigated by examining the expression of Rab25 and Rab35, two G-protein-related molecules in an ovarian cancer tissue microarray (TMA). RESULTS: OVCAR3 and OSEC2 cells were shown to express the AR and showed an increase in S-phase fraction in response to androgen treatment. Treatment of OVCAR3 cells with androgen resulted in a significant upregulation of 121 genes. These findings were confirmed for a subset of seven monomeric G-protein-related genes in both OVCAR3 and OSEC2 cells. After staining for Rab25 and Rab35, the majority of TMA sections examined showed expression for Rab25 (92%) and Rab35 (95%). The expression of Rab25 correlated with histological grade, and expression was higher in endometrioid (median histoscore 10.5) than serous (7.5) or mucinous (5.3) tumours. The expression of Rab25 correlated positively with AR expression supporting its role as an androgen responsive gene in ovarian cancer. CONCLUSIONS: These results suggest that androgens can effect expression of the oncogenic GTPases in ovarian cancer. We propose that the androgen responsive Rab35 may have clinical importance as a biomarker of AR function.

After treatment for cervical intraepithelial neoplasia (CIN), in the UK women who are cytology-negative, high-risk (HR) human papilloma virus (HPV) positive are referred to colposcopy. This pilot study assessed the incidence of residual/recurrent CIN and the diagnostic accuracy of colposcopy with dynamic spectral imaging (DSI) mapping in their detection.This was a prospective service evaluation carried out in a UK National Health Service (NHS) colposcopy clinic. All women, referred with negative cytology/HR-HPV positive result following treatment for CIN from March 2013 until November 2014, who were examined with the DSI digital colposcope were included. We excluded 3 cases because of poor-quality imaging from user errors. Everyday clinical practice was followed. Initial colposcopic impression, DSI map indication, and biopsy site selections were recorded. CIN2+ was considered the primary outcome and CIN of any grade a secondary outcome.A total of 105 women were included of which 5 (4.8%) had CIN2+ histology and 24 (22.9%) had CIN1. Pre-DSI map colposcopy suggested normal/low grade in all 5 of the CIN2+ cases and DSI suggested high-grade (HG) CIN in 4 of the 5 cases. Sensitivity of standard colposcopy for CIN2+ was 0%, improving to 80% with the incorporation of the DSI map.The CIN burden in this population is higher than previously expected. Colposcopic identification of HG CIN appears to improve significantly with DSI in this cohort leading to refinement in patient management. A larger, multicentric prospective study (DySIS colposcopy 2) is planned to confirm these initial findings.