Top 10 research priorities for digital technology for adolescents and young persons with inflammatory bowel disease: Results of a James Lind Alliance Priority Setting Partnership.

OBJECTIVES: Priority Setting Partnerships (PSP's) using the James Lind Alliance (JLA) methodology, bring together health professionals, patients and parents/carers to identify and prioritise unanswered questions that can be addressed by future research projects. To identify and prioritise the top 10 unanswered research priorities in digital technology for adolescents and young people (AYP) with inflammatory bowel disease (IBD). METHODS: A steering group (SG) consisting of AYP with IBD, their parents/carers, representatives from two charities (Crohn's & Colitis UK, Crohn's in Childhood Research Association), patient information forum and paediatric and adult and primary care healthcare professionals was established in 2021. The SG agreed the protocol, and scope of the PSP and oversaw all aspects. SG meetings were chaired by a JLA advisor and followed the established JLA methodology. RESULTS: The initial survey generated 414 in-scope questions from 156 respondents, thematically categorised into 10 themes and consolidated into 92 summary questions by the SG. A comprehensive literature review followed by SG deliberation narrowed the unanswered summary questions to 45, for the interim prioritising survey. One hundred and two respondents ranked their top 10 research questions. Outputs generated top 18 research priorities presented at a final virtual prioritisation workshop, facilitated by JLA advisors and attended by key stakeholders, ranked into top 10 research priorities. DISCUSSION: The top 10 research priorities will encourage researchers to undertake research that addresses these areas of unmet need for AYP living with IBD, their parents/carers and their healthcare professionals, thereby facilitating improved patient care.

MIRRORS: a prospective cohort study assessing the feasibility of robotic interval debulking surgery for advanced-stage ovarian cancer.

OBJECTIVE: To establish the feasibility and safety of robotic interval debulking surgery following the MIRRORS protocol (robot-assisted laparoscopic assessment prior to robotic or open surgery) in women with advanced-stage ovarian cancer. MIRRORS is the first of three planned trials: MIRRORS, MIRRORS-RCT (pilot), and MIRRORS-RCT. METHODS: The participants were patients with stage IIIc-IVb epithelial ovarian cancer undergoing neo-adjuvant chemotherapy, suitable for interval debulking surgery with a pelvic mass ≤8 cm. The intervention was robot-assisted laparoscopic assessment prior to robotic or open interval debulking surgery (MIRRORS protocol). The primary outcome was feasibility of recruitment, and the secondary outcomes were quality of life (EORTC QLQC30/OV28, HADS questionnaires), pain, surgical complications, complete cytoreduction rate (%), conversion to open surgery (%), and overall and progression-free survival at 1 year. RESULTS: Overall, 95.8% (23/24) of patients who were eligible were recruited. Median age was 68 years (range 53-83). All patients had high grade serous histology and were BRCA negative. In total, 56.5% were stage IV, 43.5% were stage III, 87.0% had a partial response, while 13.0% had stable disease by RECIST 1.1. Median peritoneal cancer index was 24 (range 6-38). Following MIRRORS protocol, 87.0% (20/23) underwent robotic interval debulking surgery, and 13.0% (3/23) had open surgery. All patients achieved R<1 (robotic R0=47.4%, open R0=0%). No patients had conversion to open. Median estimated blood loss was 50 mL for robotic (range 20-500 mL), 2026 mL for open (range 2000-2800 mL) (p=0.001). Median intensive care length of stay was 0 days for robotic (range 0-8) and 3 days (range 3-13) for MIRRORS Open (p=0.012). The median length of stay was 1.5 days for robotic (range 1-17), 6 days for open (range 5-41) (p=0.012). The time to chemotherapy was as follows 18.5 days for robotic (range 13-28), 25 days for open (range 22-28) (p=0.139). CONCLUSIONS: Robotic interval debulking surgery appears safe and feasible for experienced robotic surgeons in patients with a pelvic mass ≤8 cm. A randomized controlled trial (MIRRORS-RCT) will determine whether MIRRORS protocol has non-inferior survival (overall and progression-free) compared with open interval debulking surgery.

Adipocytokines and disease progression in endometrial cancer: a systematic review.

The objective of the study was to document the effect of adipocytokines on endometrial cancer progression. A search of the databases CINAHL, Medline, PubMed, Cochrane, Web of Science, Embase and Google Scholar was performed for English language articles from January 2000 to December 2020 using the keywords: (Endometrial cancer) AND (progression OR metastasis) AND (adipocytokine OR adiponectin OR leptin OR visfatin OR IL-6 OR TNF-α OR adipokine OR cytokine). Forty-nine studies on adipocytokines have been included in this review. Adiponectin has been linked with anti-proliferative and anti-metastatic effects on endometrial cancer cells and is associated with a better prognosis. Leptin, visfatin and resistin are linked to the stimulation of endometrial cancer growth, proliferation, invasion and metastasis and are associated with worse prognosis or with a higher grade/stage of endometrial cancer. IL-6, Il-11, IL-31, IL-33, TNF-α, TGF-ß1, SDF-1 and CXCR are involved in endometrial cancer cell growth and metastasis or involved in epithelial mesenchymal transformation (EMT) or associated with advanced disease. Adipocytokines have been found to directly impact endometrial cancer cell proliferation, invasion and migration. These molecules and their signalling pathways may be used to determine prognosis and course of the disease and may also be exploited as potential targets for cancer treatment and prevention of progression.

Adipocytokines and their relationship to endometrial cancer risk: A systematic review and meta-analysis.

OBJECTIVE: To investigate the association between circulating levels of adipocytokines (adiponectin, leptin, tumour necrosis factor alpha (TNFα), interleukin 6 (IL-6)) and growth factors (insulin-like growth factor I (IGF-I) and II (IGF-II)), and the risk of endometrial cancer. METHODS: Cochrane, CINAHL, Embase, Medline and Web of Science were searched for English-language manuscripts published between January 2000 and August 2018 using the following string of words: cancer and endometrial and (obesity or BMI) and (adiponectin or TNF* or IGF-I or IGF-II or IL-6 or leptin). RESULTS: Twenty articles were included in this meta-analysis, which corresponded to 18 studies involving 2921 endometrial carcinoma cases and 5302 controls. Fourteen articles reported circulating levels for adiponectin, seven for leptin, three for TNFα, three for IL-6 and one for IGF-I. No article reported values for IGF-II. Patients with circulating adiponectin levels in the highest tertile had decreased endometrial cancer risk compared to women with levels in the lowest tertile, (summary of odds ratio (SOR) 0.51, 95% confidence interval (CI): 0.38-0.69, p < 0.00001). Women with circulating leptin concentrations in the highest tertile had increased endometrial cancer risk compared to women with concentrations in the lowest tertile (SOR 2.19, 95% CI: 1.45-3.30, p = 0.0002). There was no difference in cancer risk between participants with the highest TNFα and IL-6 levels compared to the lowest levels (SOR 1.27, 95% CI: 0.88-1.83, p = 0.20 and SOR 1.20, 95% CI: 0.89-1.63, p = 0.23, respectively). CONCLUSIONS: Endometrial cancer risk is inversely affected by adiponectin and leptin levels. There appears to be no relationship between TNFα and IL-6 and the overall risk of endometrial cancer.

COVID-19 and gynecological cancer: a review of the published guidelines.

On March 11, 2020 the COVID-19 outbreak was declared a 'pandemic' by the World Health Organization. COVID-19 is associated with higher surgical morbidity and mortality. An array of guidelines on the management of cancer during this pandemic have been published since the first reports of the outbreak. This narrative review brings all the relevant information from the guidelines together into one document, to support patient care. We present a detailed review of published guidelines, statements, comments from peer-reviewed journals, and nationally/internationally recognized professional bodies and societies' web pages (in English or with English translation available) between December 1, 2019 and May 27, 2020. Search terms included combinations of COVID, SARS-COV-2, guideline, gynecology, oncology, gynecological, cancer. Recommendations for surgical and oncological prioritization of gynecological cancers are discussed and summarized. The role of minimally invasive surgery, patient perspectives, medico-legal aspects, and clinical trials during the pandemic are also discussed. The consensus is that elective benign surgery should cease and cancer surgery, chemotherapy, and radiotherapy should continue based on prioritization. Patient and staff face-to-face interactions should be limited, and health resources used efficiently using prioritization strategies. This review and the guidelines on which it is based support the difficult decisions currently facing us in gynecological cancer. It is a balancing act: limited resources and a hostile environment pitted against the time-sensitive nature of cancer treatment. We can only hope to do our best for our patients with the resources available to us.

The role of biomarkers in endometrial cancer and hyperplasia: a literature review.

INTRODUCTION: Endometrial cancer is the most common gynaecological cancer and its incidence is rising due to increasing obesity rates. We are also seeing an increasing trend of young women diagnosed with either endometrial cancer or its precancerous state, endometrial hyperplasia. Diagnosis is dependent on invasive testing and there is no screening tool available for either general or high-risk population groups. Whilst vast amounts of research have been undertaken in higher-profile cancers such as ovarian and cervical, endometrial cancer is comparatively less investigated. AIM: In this literature review, we summarise the existing literature in understanding the role of tumour biomarkers for endometrial cancer and its preceding condition of endometrial hyperplasia. METHOD: NICE Healthcare Databases Search tool was used to search Embase, Medline and PubMed databases for relevant articles. CONCLUSION: There is currently no routinely used biomarker in endometrial cancer for diagnostic or prognostic purposes. Given the establishment of new genomic classifications of endometrial cancers, the use of biomarkers to drive therapeutic approaches will be the cornerstone for individualised cancer care in the coming decades.

Where will genetic toxicology testing be in 30 years' time? Summary report of the 25th Industrial Genotoxicity Group Meeting, Royal Society of Medicine, London, November 9, 2011.

A number of influences including legislation, industry and academia have encouraged advances in computational toxicology and high-throughput testing to probe more broadly putative toxicity pathways. The aim of the 25th United Kingdom Mutagen Society (UKEMS) Industrial Genotoxicity Group Annual Meeting 2011 was to explore current and upcoming research tools that may provide new cancer risk estimation approaches and discuss the genotoxicity testing paradigm of the future. The meeting considered whether computer modelling, molecular biology systems and/or adverse outcome pathway approaches can provide more accurate toxicity predictions and whether high-content study data, pluripotent stem cells or new scientific disciplines, such as epigenetics and adductomics, could be integrated into the risk assessment process. With close collaboration between industry, academia and regulators next generation predictive models and high-content tools have the potential to transform genetic toxicology testing in the 21st century.

MIRRORS ICG: Perfusion Assessment Using Indocyanine Green (ICG) Peritoneal Angiography during Robotic Interval Cytoreductive Surgery for Advanced Ovarian Cancer.

Indocyanine green (ICG) is a fluorescent dye used for sentinel lymph node assessment and the assessment of perfusion in skin flaps and bowel anastomoses. ICG binds serum proteins and behaves as a macromolecule in the circulation. Tumour tissue has increased vascular permeability and reduced drainage, causing macromolecules to accumulate within it. MIRRORS ICG is designed to determine whether indocyanine green (ICG) helped identify metastatic deposits in women undergoing robotic interval cytoreductive surgery for advanced-stage (3c+) ovarian cancer. Peritoneal surfaces of the abdominal and pelvic cavity were inspected under white light and near-infrared light (da Vinci Si and Xi Firefly Fluorescence imaging, Intuitive Surgical Inc.) following intravenous injection of 20 mg ICG in sterile water. Visibly abnormal areas were excised and sent to histopathology, noting IGC positivity. In total, 102 biopsies were assessed using ICG. Intravenous ICG assessment following neoadjuvant chemotherapy had a sensitivity of 91.1% (95% CI [82.6-96.4%]), a specificity of 13.0% (95% CI [2.8-33.6%]), a positive predictive value of 78.3% (95% CI [68.4-86.2%]), and a negative predictive value of 30.0% (95% CI [6.7-65.2%]) False-positive samples were seen in 9/20 patients. Psammoma bodies were noted in the histopathology reports of seven of nine of these patients with false-positive results, indicating that a tumour had been present (chemotherapy-treated disease). This study demonstrates the appearance of metastatic peritoneal deposits during robotic cytoreductive surgery following the intravenous administration of ICG in women who have undergone neoadjuvant chemotherapy for stage 3c+ advanced ovarian cancer. A perfusion assessment using indocyanine green (ICG) peritoneal angiography during robotic interval cytoreductive surgery for advanced ovarian cancer did not clinically improve metastatic disease identification in patients with high-volume disease. The use of ICG in patients with excellent response to chemotherapy where few tumour deposits remained shows some promise. The potential of molecular imaging to enhance precision surgery and improve disease identification using the robotic platform is a novel avenue for future research.

Circulating Adipocytokines and Insulin Like-Growth Factors and Their Modulation in Obesity-Associated Endometrial Cancer.

The rising global incidence of uterine cancer is linked to the escalating prevalence of obesity. Obesity results in alterations in adipocytokines and IGFs, driving cancer progression via inflammation, increased cell proliferation, and apoptosis inhibition, although the precise mechanisms are still unclear. This study examined a set of six markers, namely, adiponectin, leptin, IL6, TNFα, IGF1, and IGF2 and compared them between fifty age-matched endometrial cancer patients (study group) and non-cancer patients with benign gynaecological conditions (control group). We also assessed the relationship of these markers with obesity and explored the correlation between these markers and various tumour characteristics. In the cancer population, these markers were also assessed 24 h and 6 months post-surgery. Remarkably, low adiponectin levels were associated with a 35.8% increase in endometrial cancer risk. Interestingly, compared to control subjects where IGF levels decreased after menopause, post-menopausal women in the study group showed elevated IGF1 and IGF2 levels, suggesting a potential influence of endometrial cancer on the IGF system, particularly after menopause. Lastly, it is noteworthy that a discernible inverse relationship trend was observed in the levels of adipocytokines and IGFs 6 months post-surgery. This indicates that treatment for endometrial cancer may have a differential impact on adipocytokines and IGFs, potentially holding clinical significance that merits further investigation.

Determination of compound-specific acceptable daily intakes for 11 mutagenic carcinogens used in pharmaceutical synthesis.

The synthesis of pharmaceutical products often involves the use of reactive starting materials and intermediates. Low levels may be present in the final product as impurities and of particular concern are impurities that have mutagenic and carcinogenic potential. Regulatory guidance documents provide a general framework to minimise human exposure to these impurities; however, compound-specific recommendations are limited. Our practical experience with 11 pharmaceutical impurities is presented. The genotoxicity and carcinogenicity data are summarised and the approach used to derive an acceptable daily intake (ADI) is described for each chemical. We have highlighted the considerations and challenges associated with calculating ADIs based on available carcinogenicity data. This may provide a useful reference to others in the pharmaceutical industry regarding impurity control, where the weight of evidence indicates the chemical is a mutagenic carcinogen.

The Role of Cytokines in Epithelial-Mesenchymal Transition in Gynaecological Cancers: A Systematic Review.

Chronic inflammation has been closely linked to the development and progression of various cancers. The epithelial-mesenchymal transition (EMT) is a process involving the acquisition of mesenchymal features by carcinoma cells and is an important link between inflammation and cancer development. Inflammatory mediators in the tumour micro-environment, such as cytokines and chemokines, can promote EMT changes in cancer cells. The aim of this systematic review is to analyse the effect of cytokines on EMT in gynaecological cancers and discuss their possible therapeutic implications. A search of the databases CINAHL, Cochrane, Embase, Medline, PubMed, TRIP, and Web of Science was performed using the keywords: "cytokines" AND "epithelial mesenchymal transition OR transformation" AND "gynaecological cancer". Seventy-one articles reported that various cytokines, such as TGF-ß, TNF-α, IL-6, etc., promoted EMT changes in ovarian, cervical, and endometrial cancers. The EMT changes included from epithelial to mesenchymal morphological change, downregulation of the epithelial markers E-cadherin/ß-catenin, upregulation of the mesenchymal markers N-cadherin/vimentin/fibronectin, and upregulation of the EMT-transformation factors (EMT-TF) SNAI1/SNAI2/TWIST/ZEB. Cytokine-induced EMT can lead to gynaecological cancer development and metastasis and hence novel therapies targeting the cytokines or their EMT signalling pathways could possibly prevent cancer progression, reduce cancer recurrence, and prevent drug-resistance.

Enhanced Recovery after Uterine Corpus Cancer Surgery: A 10 Year Retrospective Cohort Study of Robotic Surgery in an NHS Cancer Centre.

Royal Surrey NHS Foundation Trust introduced robotic surgery for uterine corpus cancer in 2010 to support increased access to minimally invasive surgery, a central element of an enhanced recovery after surgery (ERAS) pathway. More than 1750 gynaecological oncology robotic procedures have now been performed at Royal Surrey NHS Foundation Trust. A retrospective cohort study was performed of patients undergoing surgery for uterine corpus cancer between the 1 January 2010 and the 31 December 2019 to evaluate its success. Data was extracted from the dedicated gynaecological oncology database and a detailed notes review performed. During this time; 952 patients received primary surgery for uterine corpus cancer; robotic: n = 734; open: n = 164; other minimally invasive surgery: n = 54. The introduction of the Da VinciTM robot to Royal Surrey NHS Foundation Trust was associated with an increase in the minimally invasive surgery rate. Prior to the introduction of robotic surgery in 2008 the minimally invasive surgery (MIS) rate was 33% for women with uterine corpus cancer undergoing full surgical staging. In 2019, 10 years after the start of the robotic surgery program 91.3% of women with uterine corpus cancer received robotic surgery. Overall the MIS rate increased from 33% in 2008 to 92.9% in 2019. Robotic surgery is associated with a low 30-day mortality (0.1%), low return to theatre (0.5%), a low use of blood transfusion and intensive care (1.8% & 7.2% respectively), low conversion to open surgery (0.5%) and a reduction in median length of stay from 6 days (in 2008) to 1 day, regardless of age/BMI. Robotic survival is consistent with published data. Introduction of the robotic program for the treatment of uterine cancer increased productivity and was associated with a highly predicable patient pathway of care, for high-risk patients, with reduced demands on health services. Future health care commissioning should further expand access to robotic surgery nationally for women with uterine corpus cancer.

Minimally invasive pelvic exenteration for gynaecological malignancy: A single-centre case series and review of the literature.

For those with certain recurrent gynaecological cancers where primary management such as chemo-radiotherapy has failed, or in cases of recurrence following primary surgery, pelvic exenteration (PE) is considered the only curative option. Whilst initially considered a morbid procedure, improved surgical techniques, advancing technology, and nuanced reconstructive options have facilitated more radical resections and improved morbidity and mortality. Open PE remains the gold standard approach, however, minimally invasive techniques for PE may lessen morbidity whilst achieving the same oncological outcomes. The objective of this study was to assess the feasibility and safety of minimally invasive PE with a laparoscopic or robot-assisted approach. We also performed a review of the literature on robot-assisted PE which has not been widely reported for cases of recurrent gynaecological malignancy. Between 2015 and 2021six minimally invasive PE were performed. All patients underwent extensive multi-disciplinary assessment and counselling pre-operatively. Patient characteristics, treatment indication, perioperative data, short-term complications, and histological outcomes were recorded. There were two anterior exenterations, three posterior exenterations and one total exenteration performed. The primary cancer stage varied from stage 1a-3b. Five out of six patients had pre-operative chemo-radiotherapy. The average operative time (including surgical docking) was 600 min. Mean blood loss was 400 mL and the average length of stay was eight days. Enhanced recovery practices were used where possible. There were no intraoperative complications and one major post-operative complicationwhich was breakdown of an inferior gluteal artery perforator flap perineal reconstruction. All patients had negative margins at post-operative histopathology. All patients are alive and recurrence free at follow-up, but long-term outcome data is needed. This initial case series suggest that minimally invasive pelvic exenterationcan feasibly be performed in place of open pelvic exenteration. Furthermore, our findings suggest this may be a safe alternative as we report similar findings to the existing literature, however no firm conclusions can be drawn at such an early stage. Long term follow-up data and a larger cohort study will be needed to establish non-inferiority to open PE.

Would extirpative pelvic surgery improve survival in gynecological metastases of lung cancer? Case report and review of the literature.

Lung cancer is the 3rd most common cancer in the UK and the numbers of new cases increase every year. In contrast to gastrointestinal tumours and breast cancer, lung cancer, metastases to the female genital tract are incredibly rare with only five cases reported with uterine metastases on review of the published English literature. We report an interesting case of successful ongoing management of metastatic lung cancer to the pelvis along with an extensive literature review. A 47-year-old lady with recurrent respiratory tract symptoms and chest pain was diagnosed with advanced stage non-small-cell lung cancer (Stage T4N2M1A). Five years following diagnosis and several cycles of chemotherapy and radiotherapy, aged 52, she complained of post-menopausal bleeding and pelvic discomfort. An endometrial biopsy confirmed a malignancy morphologically and immunohistochemically similar to her lung adenocarcinoma, in keeping with metastatic disease. She underwent robotic surgery to excise the pelvic organs and successfully gain local disease control. The patient remains clinically stable 3 years following hysterectomy. Although metastases of lung cancer to uterus are very rare, any patient with abnormal uterine bleeding with known cancer should be investigated thoroughly to rule out metastatic disease. Combined multimodal treatment as in this case may increase overall survival.

A patient-clinician James Lind Alliance partnership to identify research priorities for hyperemesis gravidarum.

OBJECTIVE: There are many uncertainties surrounding the aetiology, treatment and sequelae of hyperemesis gravidarum (HG). Prioritising research questions could reduce research waste, helping researchers and funders direct attention to those questions which most urgently need addressing. The HG priority setting partnership (PSP) was established to identify and rank the top 25 priority research questions important to both patients and clinicians. METHODS: Following the James Lind Alliance (JLA) methodology, an HG PSP steering group was established. Stakeholders representing patients, carers and multidisciplinary professionals completed an online survey to gather uncertainties. Eligible uncertainties related to HG. Uncertainties on nausea and vomiting of pregnancy and those on complementary treatments were not eligible. Questions were verified against the evidence. Two rounds of prioritisation included an online ranking survey and a 1-hour consensus workshop. RESULTS: 1009 participants (938 patients/carers, 118 professionals with overlap between categories) submitted 2899 questions. Questions originated from participants in 26 different countries, and people from 32 countries took part in the first prioritisation stage. 66 unique questions emerged, which were evidence checked according to the agreed protocol. 65 true uncertainties were narrowed via an online ranking survey to 26 unranked uncertainties. The consensus workshop was attended by 19 international patients and clinicians who reached consensus on the top 10 questions for international researchers to address. More patients than professionals took part in the surveys but were equally distributed during the consensus workshop. Participants from low-income and middle-income countries noted that the priorities may be different in their settings. CONCLUSIONS: By following the JLA method, a prioritised list of uncertainties relevant to both HG patients and their clinicians has been identified which can inform the international HG research agenda, funders and policy-makers. While it is possible to conduct an international PSP, results from developed countries may not be as relevant in low-income and middle-income countries.

Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II.

PURPOSE: The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS: GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS: From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION: Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.

Molecular characteristics and risk factors in endometrial cancer: what are the treatment and preventative strategies?

OBJECTIVES: The growing prevalence of endometrial cancer has made it necessary to characterize its molecular and clinical properties and to develop new strategies in treating this disease. A number of molecular and genetic events have been observed in endometrial cancers, which have enabled us to have a better understanding of the biology and development of the disease. For example, PTEN/AKT pathway and its downstream targets and the mTOR (mammalian target of rapamycin) pathway have been shown to play an important role in endometrial cancer pathogenesis. Novel therapies, such as drugs that target cellular pathways, for example, mTOR inhibitor deforolimus, an analog of rapamycin, have been developed and used in clinical trials to treat women with progressive endometrial cancer. This review outlines the data on the molecular and translational aspects of endometrial cancers and the risk factors. METHODS: A literature search was performed using PubMed and OvidSP entering the words endometrial cancer and molecular characteristics and endometrial cancer and risk factors. RESULTS: An evidence-based summary of the data on the molecular and translational aspects of endometrial cancers and risk factors was obtained. CONCLUSIONS: Clear understanding of the cellular and molecular pathways and risk factors involved in endometrial tumorigenesis may allow us to identify women at risk of developing endometrial cancer and possibly intervene to prevent cancer development.

The need for post-operative vasopressor infusions after major gynae-oncologic surgery within an ERAS (Enhanced Recovery After Surgery) pathway.

BACKGROUND: Hypotension following major abdominal surgery is common, and once hypovolaemia has been optimally treated, is often due to vasodilation which can be treated with vasopressor infusions. There is unpredictability in the dose and duration of post-operative vasopressor infusions, and factors associated with this have not been determined. METHODS: We present a case series of consecutive patients who received major gynae-oncology surgery delivered within an Enhanced Recovery After Surgery (ERAS) pathway at a single institution. Patients were electively admitted from theatre directly to the intensive care unit (ICU). Data was collected prospectively into electronic databases (Philips ICCA, Wardwatcher) and then retrospectively collated and appropriate statistical analyses were performed. In the absence of a consensus definition of vasoplegia, we, necessarily arbitrarily, chose a noradrenaline dose of > 0.1 mcg/kg/min at 08:00 on the first post-operative day. The rationale is that this would be more than would typically be expected to counteract the vasodilatory effects of epidural analgesia, which is commonly used at our institution. RESULTS: Data was collected from 324 patients, all treated between February 2014 and July 2016. The average age was 67 years and 39% received neoadjuvant chemotherapy. The commonest tumour type was ovarian (58%). The median estimated blood loss was 800 ml and epidural analgesia was used in 71%. Fifty per cent received post-operative vasopressor infusions: factors associated with this included epidural use and estimated blood loss. Nineteen per cent met our criteria for vasoplegia: factors associated with this included CRP on post-operative day 1 and P-POSSUM morbidity score. Hospital and ICU length of stay was prolonged in those who had vasoplegia. CONCLUSIONS: Patients commonly receive vasopressors following major gynae-oncologic surgery, and this can be at relatively high doses. Clinical factors only accounted for a minority of the variability in vasopressor usage-suggesting considerable biological variability. Optimal care of patients having major abdomino-pelvic surgery may include advanced haemodynamic monitoring and ready availability of infused vasopressors, in a suitable environment.