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.

Long term oncologic and reproductive outcomes after robot-assisted radical trachelectomy for early-stage cervical cancer. An international multicenter study.

OBJECTIVES: Long term outcomes following fertility sparing robot-assisted radical trachelectomy (RRT). METHODS: A retrospective study of consecutive women selected for RRT between 2007 and 2019 at five referral centres. Generally used selection criteria for fertility-sparing surgery were applied. Oncologic, reproductive and long-term clinical data were analysed. RESULTS: Of the 166 included women, 149 completed a RRT. Median tumor size was 9 mm (range 3-20 mm), 111 women (75%) had FIGO 2009 stage IB1 cancer and 4.8% were node positive. At a median follow up of 58 months, 12 of all women (7.2%) and 9 of 149 women (6%) who underwent completed RRT with fertility preservation had recurred and two had died. 70 of 88 women (80%) who attempted to conceive succeeded, resulting in 81 pregnancies that progressed beyond the first trimester and 76 live births of which 54 (70%) were delivered at term and 65 (86%) delivered after gestational week 32. A short postoperative cervical length was associated with impaired fertility. A late secondary hysterectomy was necessary in four women due to persistent bleeding (n = 2), hematometra due to a cervical stenosis (n = 1) and recurrent dysplasia (n = 1). CONCLUSION: In this long-term follow-up of RRT the recurrence rate is comparable to larger individual studies of minimally invasive or vaginal radical trachelectomy with similar risk profile and follow up. The high pregnancy rate and low rate of premature delivery before 32 weeks GA may promote the use of robot-assisted approach.

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.

Engrailed-2 (EN2) - a novel biomarker in epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer is a common malignancy, with no clinically approved diagnostic biomarker. Engrailed-2 (EN2) is a homeodomain-containing transcription factor, essential during embryological neural development, which is dysregulated in several cancer types. We evaluated the expression of EN2 in Epithelial ovarian cancer, and reviewed its role as a biomarker. METHODS: We evaluated 8 Epithelial ovarian cancer cell lines, along with > 100 surgical specimens from the Royal Surrey County Hospital (2009-2014). In total, 108 tumours and 5 normal tissue specimens were collected. En2 mRNA was evaluated by semi-quantitative RT-PCR. Histological sub-type, and platinum-sensitive/-resistant status were compared. Protein expression was assessed in cell lines (immunofluorescence), and in > 150 tumours (immunohistochemistry). RESULTS: En2 mRNA expression was elevated in serous ovarian tumours compared with normal ovary (p < 0.001), particularly in high-grade serous ovarian cancer (p < 0.0001) and in platinum-resistant tumours (p = 0.0232). Median Overall Survival and Progression-free Survival were reduced with high En2 expression (OS = 28 vs 42 months, p = 0.0329; PFS = 8 vs 27 months; p = 0.0004). Positive cytoplasmic EN2 staining was demonstrated in 78% of Epithelial ovarian cancers, with absence in normal ovary. EN2 positive high-grade serous ovarian cancer patients had a shorter PFS (10 vs 17.5 months; p = 0.0103). CONCLUSION: The EN2 transcription factor is a novel ovarian cancer biomarker. It demonstrates prognostic value, correlating with worse Overall Survival and Progression-free Survival. It is hoped that further work will validate its use as a biomarker, and provide insight into the role of EN2 in the development, progression and spread of ovarian cancer.

Isolated Urethral Metastasis From a Primary Ovarian Malignancy.

BACKGROUND: Epithelial ovarian cancer (EOC) is the deadliest of gynaecological cancers, often manifesting itself at a later stage (stage 3 and 4). Metastases and recurrences tend to be limited to the abdominopelvic cavity, and cutaneous metastases are rare. CASE SUMMARY: We report an interesting case of a 51-year-old who presented 2 years after her initial treatment with surgery and adjuvant chemotherapy for a stage IIB with an isolated recurrence in the external urethral meatus. CONCLUSION: This case highlights the need for clinicians and patients to remain vigilant during follow-up visits to rule out recurrences despite nonspecific symptoms reported by patients.

Effect of blue dye guided lymph channel ligation on the surgical morbidity of groin lymphadenectomy for vulval cancer: a feasibility study.

Inguinal lymphadenectomy has significant morbidity. Blue dye-guided lymph channel ligation is an effective technique for resolving lymphocele. This was a feasibility study in a preventative setting. Patients with vulval cancer requiring bilateral inguinal lymphadenectomy were recruited. After lymphadenectomy, patent blue V dye was injected and the severed lymph channels leaking blue dye, on the randomly-designated side were ligated. The median age was 72.5 years and the median body mass index was 25. The median lymph node harvest was 18.5. There were no significant surgical procedural differences between the right and the left sides. There was no significant difference between the two arms in terms of the duration or the volume of drainage and post-operative complications. All patients were alive at the follow-up period of 40.5 months. In this feasibility study, blue dye-guided lymph channel ligation did not significantly impact on post-operative outcomes. Impact statement What is already known on this subject? Lymph channel ligation with blue dye-guidance is an effective strategy for managing recalcitrant inguinal lymphocyst. This strategy was prospectively-studied in a small series of patients with non-gynaecological cancers. This particular study by Nakamura et al. ( 2011 ) revealed that such a strategy might be efficacious in reducing wound drain output. What do the results of this study add? Our study is the first study to assess this technique exclusively in vulval cancer. Blue dye-guided lymph channel ligation at the time of inguinal lymphadenectomy does not appear to reduce wound drainage. However, this study suggests that primary lymphocyst predominantly results from inflammatory exudates, whereas persistent secondary lymphocysts are likely to result from lymphorrhoea. What are the implications of these findings for clinical practice and/or further research? Future studies, which aim to reduce the morbidity of open inguinal lymphadenectomy, should employ a composite strategy to reduce inflammatory secretions. In addition, a biochemical and cytological analysis on lymphocysts at various time points should be performed to characterise the natural history of groin lymphocysts.

Lockjaw from a metastatic uterine leiomyosarcoma- case report and review of the literature.

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.

The prognostic significance of specific HOX gene expression patterns in ovarian cancer.

HOX genes are vital for all aspects of mammalian growth and differentiation, and their dysregulated expression is related to ovarian carcinogenesis. The aim of the current study was to establish the prognostic value of HOX dysregulation as well as its role in platinum resistance. The potential to target HOX proteins through the HOX/PBX interaction was also explored in the context of platinum resistance. HOX gene expression was determined in ovarian cancer cell lines and primary EOCs by QPCR, and compared to expression in normal ovarian epithelium and fallopian tube tissue samples. Statistical analysis included one-way ANOVA and t-tests, using statistical software R and GraphPad. The analysis identified 36 of the 39 HOX genes as being overexpressed in high grade serous EOC compared to normal tissue. We detected a molecular HOX gene-signature that predicted poor outcome. Overexpression of HOXB4 and HOXB9 was identified in high grade serous cell lines after platinum resistance developed. Targeting the HOX/PBX dimer with the HXR9 peptide enhanced the cytotoxicity of cisplatin in platinum-resistant ovarian cancer. In conclusion, this study has shown the HOX genes are highly dysregulated in ovarian cancer with high expression of HOXA13, B6, C13, D1 and D13 being predictive of poor clinical outcome. Targeting the HOX/PBX dimer in platinum-resistant cancer represents a potentially new therapeutic option that should be further developed and tested in clinical trials.

Decidualisation of ovarian endometriomas in pregnancy: a management dilemma. A case report and review of the literature.

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.

Interval debulking surgery following neo-adjuvant chemotherapy for stage IVB ovarian cancer using neutral argon plasma (PlasmaJet™).

OBJECTIVE: We present a novel surgical approach to ovarian cancer debulking using neutral argon plasma (PlasmaJet™). CASE HISTORY: A 48 year-old woman diagnosed with FIGO stage IVB grade 3 serous epithelial ovarian carcinoma received three cycles of neoadjuvant chemotherapy with carboplatin and paclitaxel. OPERATIVE TECHNIQUE: Dissection and radical debulking surgery were performed using PlasmaJet™ as previously described [1,2]. This included diaphragmatic and abdominal peritoneal stripping, supra-colic omentectomy, tumour ablation on the small and large intestines and mesentery, pelvic and para-aortic lymphadenectomy. RESULTS: The only post-operative complication was a superficial wound breakdown, which healed by secondary intention. She remains well two years after surgery, with no sign of recurrence. CONCLUSION: In this case, PlasmaJet™ facilitated diaphragmatic peritoneal stripping as well as dissection of tissue close to bowel and major vessels. Further study is required to assess whether this device can reduce the need for bowel resection while achieving complete cytoreduction.

Cerebral oedema following robotic surgery: a rare complication.

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.

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.

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.

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.

Combined activity of oridonin and wogonin in advanced-stage ovarian cancer cells: sensitivity of ovarian cancer cells to phyto-active chemicals.

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.

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 combination of second trimester oral metronidazole and no sexual intercourse during second and third trimester may reduce late miscarriage and premature delivery after fertility sparing radical trachelectomy.

OBJECTIVES: Women with a previous trachelectomy have an increased risk of premature delivery and second trimester miscarriage. In this study we aim to evaluate factors and regimes possibly affecting the risk for prematurity following fertility sparing robotic radical trachelectomy (RRT) in cervical cancer. METHODS: A retrospective study of the reproductive outcome following RRT with a cervical cerclage performed at one of four academic centers between 2007 and 2019. Factors possibly related to premature delivery, such as postoperative non-pregnant cervical length, previous vaginal deliveries, preservation of the uterine arteries, and the use of a second trimester oral metronidazole/no sexual intercourse regime, were assessed. RESULTS: 109 women remained for analyses after excluding recurrences before pregnancy (n = 8), secondary hysterectomy (n = 2), and women with less than six months follow up (n = 10). 74 pregnancies occurred in 52/71 women attempting to conceive, 56 of which developed past the first trimester. Two of 22 women (9%) who were prescribed an oral metronidazole regime (400 mg × 2 from gestational week 15 + 0 to 21 + 6 and abstaining from sexual intercourse for the duration of the pregnancy) had a premature delivery, compared with 13/31 (42%) where the regime was not applied (p = 0.009). The association remained after regression analyses including possible contributing factors as of above, none of which associated with prematurity at regression analyses (p = 0.001). CONCLUSIONS: The observed four-fold reduction in premature delivery indicates that an oral metronidazole/no sexual intercourse regime may reduce second trimester miscarriage and premature deliveries following an RRT. No association was observed for other investigated factors.

Synchronous uterine artery embolization and laparoscopic myomectomy for massive uterine leiomyomas.

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.