Integrated eicosanoid lipidomics and gene expression reveal decreased prostaglandin catabolism and increased 5-lipoxygenase expression in aggressive subtypes of endometrial cancer.

Eicosanoids comprise a diverse group of bioactive lipids which orchestrate inflammation, immunity, and tissue homeostasis, and whose dysregulation has been implicated in carcinogenesis. Among the various eicosanoid metabolic pathways, studies of their role in endometrial cancer (EC) have very much been confined to the COX-2 pathway. This study aimed to determine changes in epithelial eicosanoid metabolic gene expression in endometrial carcinogenesis; to integrate these with eicosanoid profiles in matched clinical specimens; and, finally, to investigate the prognostic value of candidate eicosanoid metabolic enzymes. Eicosanoids and related mediators were profiled using liquid chromatography-tandem mass spectrometry in fresh frozen normal, hyperplastic, and cancerous (types I and II) endometrial specimens (n = 192). Sample-matched epithelia were isolated by laser capture microdissection and whole genome expression analysis was performed using microarrays. Integration of eicosanoid and gene expression data showed that the accepted paradigm of increased COX-2-mediated prostaglandin production does not apply in EC carcinogenesis. Instead, there was evidence for decreased PGE2 /PGF2α inactivation via 15-hydroxyprostaglandin dehydrogenase (HPGD) in type II ECs. Increased expression of 5-lipoxygenase (ALOX5) mRNA was also identified in type II ECs, together with proportional increases in its product, 5-hydroxyeicosatetraenoic acid (5-HETE). Decreased HPGD and elevated ALOX5 mRNA expression were associated with adverse outcome, which was confirmed by immunohistochemical tissue microarray analysis of an independent series of EC specimens (n = 419). While neither COX-1 nor COX-2 protein expression had prognostic value, low HPGD combined with high ALOX5 expression was associated with the worst overall and progression-free survival. These findings highlight HPGD and ALOX5 as potential therapeutic targets in aggressive EC subtypes. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A retrospective observational study for the outcomes of women presenting to a colposcopy clinic with a high-grade Pap smear - Implications for a 'see and treat' approach to management.

BACKGROUND: The current Australian National Health and Medical Research Council guidelines discourage the use of 'see and treat' colposcopic management due to concerns regarding over-treatment. However, this approach has been shown to have benefits in several studies, including cost savings, elimination of loss to follow up and decreased patient anxiety. AIMS: To provide Australian data on treatment outcomes for women presenting with a high-grade Pap smear to a large metropolitan colposcopy unit and to determine whether a 'see and treat' approach would meet specified standards. MATERIALS AND METHODS: Retrospective review of women referred to the Royal Prince Alfred Hospital colposcopy unit with a high-grade smear. Patient data, colposcopy findings, treatment and pathology results were collated and analysed to determine treatment outcomes using the current 'biopsy and treat' approach. The feasibility of 'see and treat' was assessed by determining which women with high-grade colposcopy findings had high-grade disease confirmed on biopsy or excisional specimens. RESULTS: One hundred and thirty-seven women underwent either excisional or ablative treatment. Of those undergoing excisional procedures, 81.3% had high-grade dysplasia or invasive cancer, 11.6% had CIN1 and 7.1% had no dysplasia on histopathology. One hundred and twenty-one with high-grade colposcopy findings had histopathology results available. Using a 'see and treat' approach, 92.6% would have had confirmed dysplasia of any grade, while 91.7% had confirmed high-grade dysplasia. CONCLUSIONS: 'See and treat' colposcopy is feasible in the Australian setting when applied to selected patients with high-grade cytology and high-grade colposcopic findings.

Robotic versus laparoscopic hysterectomy in morbidly obese women for endometrial cancer.

Surgery is the mainstay treatment for endometrial cancer and complex atypical endometrial hyperplasia. These conditions are more common in the obese women and as such these patients pose additional risks and challenges to surgery. Laparoscopic hysterectomy (LH) is preferred over open surgery in obese patients as it reduces surgical morbidity. However, more recently, robotic-assisted hysterectomy (RH) has been used in morbidly obese patients to overcome the limitations of conventional laparoscopy. To compare the surgical outcomes of morbidly obese patients undergoing LH or RH for endometrial cancer or complex atypical hyperplasia. A retrospective analysis of morbidly obese patients (BMI > 40 kg/m2) who underwent LH or RH for endometrial cancer or complex atypical hyperplasia at the Chris O'Brien Lifehouse Gynaecological Oncology Unit from 2015 to 2019 was performed. Data was collected from the prospectively maintained gynaecology oncology database and descriptive analysis was performed. 33 (51.6%) underwent LH and 31 (48.4%) had RH. More LHs were performed 2015-2017 period, whereas there were more RHs performed in 2018-2019 period (p = 0.01). The difference between theatre time use and operating time for LH surgery compared to RH was significantly shorter (45.7 for LH versus 61.9 min for RH, p = 0.009). RH was performed more commonly when BMI was > 50 kg/m2 (p = 0.02). There has been an increase in the use of RH in morbidly obese patients, particularly for women with a BMI > 50 kg/m2.