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Thumuluru Kavitha Madhuri, Anil Tailor, Simon Butler-ManuelDepartment of Gynaecological Oncology, The Royal Surrey County Hospital, Guildford, Surrey, UKAbstract: Vulvar cancer is an uncommon disease with approximately 1000 cases reported annually in the UK. Lymph node involvement is an important prognostic indicator. Vulvectomy and bilateral groin node dissection are the preferred surgical treatments for early disease and increase survival. However, significant morbidity with lymphocyst formation and wound breakdown has been reported in more than 50% of cases. We report the first case following use of the PlasmaJet® neutral argon coagulation system to reduce postoperative lymphocyst formation.Keywords: lymphocyst formation, wound, lymphodema

Background: Carboplatin remains a first-line agent in the management of epithelial ovarian cancer (EOC). Unfortunately, platinum-resistant disease ultimately occurs in most patients. Using a novel EOC cell line with acquired resistance to carboplatin: PEO1CarbR, genome-wide micro-array profiling identified the cyclin-dependent kinase inhibitor p57(Kip2) as specifically downregulated in carboplatin resistance. Presently, we describe confirmation of these preliminary data with a variety of approaches.Methods: Cytotoxicity testing (MTT) and cell cycle blockade assessed drug responsiveness. Methylation specific PCR and pyrosequencing identified sites of promoter methylation in p57(Kip2). siRNA to p57(Kip2) was used to look at the changes in apoptosis of carboplatin treated EOC cells. EOC tissues (20 cases) were assessed for mRNA levels of p57(Kip2).Results: Carboplatin resistance was reversed using 5-aza-cytidine in vitro. Promoter methylation sites and preferential sensitivity to seliciclib were seen in PEO1CarbR cells. Silencing p57(Kip)2 decreased the apoptotic response to the effects of platinum but produced sensitisation to seliciclib. EOC biopsies indicated an association of high levels of p57(Kip2)mRNA with complete responses to chemotherapy and improved outcome.Conclusion: We conclude that p57(Kip2) is a candidate biomarker of platinum sensitivity/resistance in EOC and such cases may show preferential response to the cyclin-dependent kinase inhibitor seliciclib. [ABSTRACT FROM AUTHOR]

Background:Carboplatin remains a first-line agent in the management of epithelial ovarian cancer (EOC). Unfortunately, platinum-resistant disease ultimately occurs in most patients. Using a novel EOC cell line with acquired resistance to carboplatin: PEO1CarbR, genome-wide micro-array profiling identified the cyclin-dependent kinase inhibitor p57Kip2 as specifically downregulated in carboplatin resistance. Presently, we describe confirmation of these preliminary data with a variety of approaches.Methods:Cytotoxicity testing (MTT) and cell cycle blockade assessed drug responsiveness. Methylation specific PCR and pyrosequencing identified sites of promoter methylation in p57Kip2. siRNA to p57Kip2 was used to look at the changes in apoptosis of carboplatin treated EOC cells. EOC tissues (20 cases) were assessed for mRNA levels of p57Kip2.Results:Carboplatin resistance was reversed using 5-aza-cytidine in vitro. Promoter methylation sites and preferential sensitivity to seliciclib were seen in PEO1CarbR cells. Silencing p57Kip2 decreased the apoptotic response to the effects of platinum but produced sensitisation to seliciclib. EOC biopsies indicated an association of high levels of p57Kip2mRNA with complete responses to chemotherapy and improved outcome.Conclusion:We conclude that p57Kip2 is a candidate biomarker of platinum sensitivity/resistance in EOC and such cases may show preferential response to the cyclin-dependent kinase inhibitor seliciclib. [ABSTRACT FROM AUTHOR]

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.

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.

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 Vinci TM 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.

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., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Background: Leiomyosarcoma (LMS) is a malignant tumour formed of cells with distinct smooth muscle features. Leiomyosarcomas rarely metastasise to the oral cavity and this literature review details all reported cases of metastasis to the mandible found in the literature. This offers a unique perspective by specifying mandible as the site of metastasis of leiomyosarcoma., Case Presentation: A 53-year-old female presented to her General Practitioner (GP) with heavy menstrual bleeding and was diagnosed with multiple fibroids. Folowing a hysterectomy and removal of both tubes and ovaries for these symptomatic uterine fibroids, an incidental diagnosis of low grade leiomyosarcoma was made. A CT scan found no evidence of residual or metastatic disease and no further treatment was deemed necessary. 6 months later she presented to A & E with a numb lower lip but it took another 6 months for the diagnosis of metastatic LMS to the mandible to be made., Discussion: Leiomyosarcomas are aggressive tumours which are liable to metastasise and therefore have a poor prognosis. An extensive literature review was undertaken to explore the frequency of metastasis in the maxillo-facial region., Conclusions: Although metastasis to the oral region is very rare as suggested from the literature review, when patients present with unusual symptoms after a diagnosis of LMS, physicians should be aware of the possibility of LMS metastases.

Introduction: Increased progesterone levels during pregnancy may cause decidualisation of endometriomas mimicking malignancies on radiology and causing management dilemmas., Case: An ovarian cyst was detected in a 33-year-old woman at her routine 12-week gestation ultrasound scan. By 18 weeks, the unilocular mass was increasing in size with features suggestive of early ovarian malignancy. The cyst was monitored throughout pregnancy and caesarean section at 38 weeks delivered a healthy male. Histology confirmed a decidualised endometrioma and benign dermoid cyst with no evidence of malignancy., Literature Review: The evidence for decidualised ovarian endometriomas in pregnancy was explored; 14 papers were identified, which reported 26 cases, excluding our index case. Of the 27 cases, 19 (70%) were managed surgically, 4 of which were delayed till caesarean section with concomitant cyst excision; 8 cases were managed conservatively through serial monitoring of the cyst, which spontaneously regressed following delivery., Conclusion: Surgical management of the cyst provides histological diagnosis but may introduce risks to mother and fetus; a conservative approach may cause anxiety but limits interventions. Elective caesarean section following monitoring throughout pregnancy may bridge the gap between surgical and purely conservative approaches if appropriate. Limited available evidence makes a definitive decision regarding management difficult. Decidualisation should be considered as a differential for suspicious ovarian lesions in pregnancy.

Introduction: We present an unusual complication following robotic assisted radical hysterectomy., Case Report: A 51-year-old female with stage 1B1 cervical cancer underwent a robotic assisted radical hysterectomy. The procedure was prolonged with difficulties dissecting the left parametrium and vaginal fornix with persistent bleeding from the left vaginal vault. Post-operatively the patient was electively sedated and ventilated. Extubation was difficult due to patient agitation but achieved on day 2. Agitation persisted and a head CT scan was performed and a diagnosis of cerebral oedema was made., Discussion: Factors contributing to this case include prolonged operating time, prolonged Trendelenburg position with high pressures of CO2 pneumoperitoneum and excessive blood loss. These factors may contribute to poor cerebral venous outflow, increasing intracranial pressure leading to increased risk of cerebral oedema., Conclusion: The mechanics of robotic assistance may be used to reduce these risks by significantly reducing intra-abdominal pressure improving venous return. The use of robotics in surgery has been increasing over the last 10 years, and the benefits have been well documented. We present an unusual complication following robotic assisted radical hysterectomy performed for cervical cancer.

Background: Epithelial Ovarian Cancer (EOC) is the second most common gynaecological cancer and accounts for more deaths than all gynaecological cancers combined. Despite extensive research, progress has been slow in understanding the pathobiology. EOC is identified as a heterogeneous malignancy with various histological subtypes. It is now well known that these different histological subtypes show differences in terms of presentation, response to treatment, immunohistochemical (IHC) reactivity and molecular profiling. Cell cycle deregulation is key in cancer development and there is some evidence in the literature that this is relevant to the problem of EOC and the development of drug resistant disease. The need to identify prognostic markers has led to several gene profiling studies using tumour tissue with equivocal results. p57kip2 is one such cell cycle regulator and its functions are being explored as recent research has shown that it is more than just a negative regulator of the cell cycle., Aims: The aim of this review is to evaluate the literature around the IHC expression of p57kip2 in EOC., Methods: Systematic review of the literature focussing on clinical outcome and immunohistochemical expression in epithelial ovarian cancer., Results: Four papers are discussed in this review and have shown great variation in IHC expression of p57kip2 in EOC. These studies incorporated different histological subtypes of EOC. However they all suggest that p57kip2 has a significant role in prognosis and its therapeutic indication needs to be studied. Multicentre collaborative studies on individual histological subtypes might provide more data and help to increase the number of cases especially for rarer tumours.

The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development. Here we review a number of recent studies showing that HOX genes are strongly expressed in ovarian cancer, and that in some cases the expression of specific HOX genes is sufficient to confer a particular identity and phenotype upon cancer cells. We also review the recent advances in elucidating the different functions of HOX genes in ovarian cancer. A literature search was performed using the search terms HOX genes (including specific HOX genes), ovarian cancer and oncogenesis. Articles were accessed through searches performed in ISI Web of Knowledge, PubMed and ScienceDirect. Taken together, these studies have shown that HOX genes play a role in the oncogenesis of ovarian cancer and function in the inhibition of apoptosis, DNA repair and enhanced cell motility. The function of HOX genes in ovarian cancer oncogenesis supports their potential role as prognostic and diagnostic markers, and as therapeutic targets in this disease.

The initial response rates of advanced-stage epithelial ovarian cancer to the chemotherapeutic agents carboplatin and paclitaxel are high. However, once drug resistance develops, further chemotherapy is less effective. The objective of this study is to investigate the anti-proliferative activity of the phyto-active chemicals (PACs) oridonin and wogonin in chemo-resistant epithelial ovarian cancer cells. Primary cell cultures from the ascitic fluid of three patients at diagnosis, two patients chemo-resistant to carboplatin and paclitaxel, and one patient treated with letrozole for breast cancer were studied and compared to the ovarian cancer cell lines A2780 and PTX10, by cell viability assay (MTS). Effects on cell cycle modulation and apoptosis were examined by flow cytometry and Western blot analysis (WB). WB was further conducted to investigate protein expressions altered by PACs. The results show that IC(50) of the primary cultures ranged from 0.6 to 5.4 μg/ml for oridonin and 0.3-12.7 μg/ml for wogonin. The paclitaxel-resistant cell line PTX10 was more sensitive to each of the PACs than the chemo-sensitive cell line A2780. Of particular interest is that in combination, the two PACs were synergistic in their cytotoxicity to five of six of the primary cultures and to both the cell lines (combination indices of 0.39-0.95). The inhibition is attributable to apoptosis and cell cycle modulation induced by the PACs as demonstrated in A2780 and PTX10. Up-regulation of the functional p53 protein in A2780 and down-regulation of Akt protein in PTX10 have in part contributed to the apoptosis. These findings suggest that oridonin and wogonin may have activity in ovarian cancer following its development of resistance to carboplatin and paclitaxel.

Uterine leiomyomas remain the commonest cause of menorrhagia and frequently cause pressure symptoms. Management of leiomyomas depends on the presenting symptoms, size, location, number of myomas, and the patient's desire to retain her uterus, fertility, or both. We present the first case of laparoscopic myomectomy for a fibroid measuring 30cm in maximum diameter.

Background: Teratomas are the commonest germ cell tumours and are most frequently found in the testes and ovary. Extragonadal teratomas are rare and mainly occur in midline structures. Uterine teratomas are extremely rare with only a few previous case reports, usually involving mature teratomas of the uterine cervix., Case Presentation: We report an 82-year-old lady presenting with post-menopausal bleeding. Initial investigations revealed a benign teratoma of the uterus which was removed. Her symptoms persisted and a recurrent, now malignant, teratoma of the uterine corpus was resected at hysterectomy. Six months after surgery she relapsed with para-aortic lymphadenopathy and was treated with a taxane, etoposide and cisplatin-containing chemotherapy regimen followed by retroperitoneal lymph node dissection., Conclusion: In this report we discuss the aetiology, diagnosis and management of uterine teratomas, and review previous case studies.