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Objective To assess the clinical efficacy of the levonorgestrel intrauterine system (LNG-IUS) in the treatment of early-stage endometrial cancer in elderly morbidly obese women, whose multiple co-morbidities made the standard surgical treatment too risky to undertake. Methods A retrospective review was conducted and case series reports were prepared of all women diagnosed with endometrial cancer, from April 2011 to December 2016 at the Queen's Hospital, London, to identify women unfit for surgery and treated with the LNG-IUS. Results Out of 438 women with endometrial cancer, Eight women with early-stage endometrial cancer were deemed unfit for surgery and underwent treatment with the LNG-IUS. All had grade 1 endometrioid endometrial adenocarcinoma, radiologically staged as 1a. Four women died of their co-morbidities, not related to endometrial cancer. One of them had 68 months of progression-free survival before death due to co-morbidities. One patient required a hysterectomy after 32 months of treatment with LNG-IUS and oral progestogens due to heavy vaginal bleeding. Three women have continued the LNG-IUS treatment with no evidence of progressive disease symptoms till date at a mean follow-up of 35.7 months. Conclusion For women with multiple co-morbidities, the LNG-IUS offers an effective and safe treatment for early-stage, low-grade endometrial cancer, with no cases of symptomatic progression reported in our case series. In the frail and elderly, where the quality of life is of paramount importance, surgical treatment may not offer additional long-term survival benefits.

Objective To investigate the rate of asymptomatic recurrence of stage 1 endometrioid endometrial cancer and assess the role of routine hospital follow-up after treatment.Methods We performed a retrospective case-note review study of women who were diagnosed with stage 1 endometrioid endometrial adenocarcinoma at Queen’s Hospital, Romford, between January 2008 and December 2016.Results We included 299 patients with a median follow-up period of 44.4 months. All the patients underwent total hysterectomy and bilateral salpingo-oophorectomy. Adjuvant radiotherapy was offered to the patients subsequent to discussions in the multidisciplinary team meeting in accordance with the risk stratification criteria. There was no significant correlation between the risk factors and disease recurrence. In total, 11 patients presented with recurrent disease with original staging: 1a, n=6/199; and 1b, n=5/100. Four patients presented with vaginal bleeding due to vault recurrence and one patient with abdominal pain due to pelvic mass. Locoregional recurrence was an incidental finding in two other patients. Four patients presented with symptomatic distant metastases to the lung (n=2), liver (n=1), and bone (n=1). No asymptomatic recurrences were identified on routine follow-ups, despite several hospital appointments and clinical examinations. The recurrence rate for patients with stage 1a and 1b, grade 1, and grade 2 disease was 3.53%, and that for patients with stage 1a, grade 1, and grade 2 disease was 2.7%.Conclusion Routine clinical examinations have a low yield in finding recurrence in asymptomatic women and should be questioned for their value, considering the limited resources of the National Health Service (NHS). Larger studies are required to support a stratified follow-up, which will include telephone and patient-initiated follow-up.

Objective To assess the safety of conservative management of cervical intraepithelial neoplasia grade 2 (CIN2) in women aged under 30 years. Study design A retrospective cohort study at Queen’s Hospital, London, UK. We reviewed patient records and ‘Open Exeter’ cytology results of 178 women aged less than 30 years with histologically proven CIN2 between 1st April 2014 and 31st March 2016. Analysis included rates of spontaneous regression of CIN2, the persistence of abnormality, the progression to CIN3 and cancer, duration of conservative management, and the number of patients that defaulted follow-up. Results Of 178 women, 69 women underwent primary treatment of CIN2 with large loop excision of the transformation zone (LLETZ). Nine women defaulted follow-up after their first appointment. One hundred women were managed conservatively with colposcopy, cytology and cervical biopsy. Overall 57% had successful conservative management with regression of high-grade lesion on colposcopy and negative cytology; 32% had failed conservative management and LLETZ, and 11% of women defaulted follow-up with abnormal cytology. Only 13% of women managed conservatively progressed to CIN3, with no woman developing cancer at a median follow-up of 22 months. In women with successful conservative management features of high-grade dysplasia on colposcopy resolved in a significantly shorter time-period compared to normalisation of their cytology (p = 0.021). Conclusion Conservative management of CIN2 appears reasonable and safe in women under the age of 30 years, with 57% showing regression to negative cytology. There is a significant time lag before cytology becomes negative, so early recourse to treatment based on cytology alone is not advised where colposcopy is satisfactory and reassuring.

We present findings of a cancer multidisciplinary-team (MDT) coordinated mainstreaming pathway of unselected 5-panel germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 and parallel somatic BRCA1/BRCA2 testing in all women with epithelial-OC and highlight the discordance between germline and somatic testing strategies across two cancer centres. Patients were counselled and consented by a cancer MDT member. The uptake of parallel multi-gene germline and somatic testing was 97.7%. Counselling by clinical-nurse-specialist more frequently needed &gt, 1 consultation (53.6% (30/56)) compared to a medical (15.0% (21/137)) or surgical oncologist (15.3% (17/110)) (p &lt, 0.001). The median age was 54 (IQR = 51–62) years in germline pathogenic-variant (PV) versus 61 (IQR = 51–71) in BRCA wild-type (p = 0.001). There was no significant difference in distribution of PVs by ethnicity, stage, surgery timing or resection status. A total of 15.5% germline and 7.8% somatic BRCA1/BRCA2 PVs were identified. A total of 2.3% patients had RAD51C/RAD51D/BRIP1 PVs. A total of 11% germline PVs were large-genomic-rearrangements and missed by somatic testing. A total of 20% germline PVs are missed by somatic first BRCA-testing approach and 55.6% germline PVs missed by family history ascertainment. The somatic testing failure rate is higher (23%) for patients undergoing diagnostic biopsies. Our findings favour a prospective parallel somatic and germline panel testing approach as a clinically efficient strategy to maximise variant identification. UK Genomics test-directory criteria should be expanded to include a panel of OC genes.

Objective To evaluate the incidence of underlying serious gynaecological pathology in women referred to colposcopy with post-coital bleeding. Main outcome measures. Incidence of precancer and cancer. Methods A retrospective cohort study of women referred to colposcopy at a London hospital from January 2008-March 2015. Inclusion criteria are women with post-coital bleeding and the following cervical cytology history: negative; inadequate; never had. Multinomial logistic regression was used to assess for significant risk factors for cervical dysplasia and cancer. Results Overall, 635 women with either negative cytology (n = 436/68.7%), no previous cytology (n = 175/27.6%), or inadequate cytology (n = 24/3.8%) were referred to colposcopy for post-coital bleeding. The median age is 35 years (S.D. = 9.7 years). In 256 (40.3%) women, no cause was detected, and 322 (50.7%) women had a benign cause. Overall, 42 (6.6%) women had low-grade dysplasia, and eleven women had high-grade dysplasia (1.7%). Four women (0.6%) had cervical cancer; clinically evident cancer on speculum examination (n = 3); micro-invasive cancer (n = 1). Current smokers were significantly more likely to have HPV atypia (p = 0.015) or cervical intraepithelial neoplasm grade 1 (CIN1) p = 0.003. Advancing age was a significant risk factor for cervical cancer (p = 0.037). Conclusion All women with post-coital bleeding need an urgent speculum examination to rule out frank cervical cancer. Although most women had a benign cause for post-coital bleeding, around 2% had a colposcopy-aided diagnosis of either cervical precancer or cancer; therefore, referral of symptomatic women deserves consideration. HPV testing may reduce referrals to colposcopy for post-coital bleeding due to non-significant pathology in the future.

ObjectiveThe Chemotherapy Response Scoring (CRS) system was developed to enable reproducible reporting of histologic tumor response in interval debulking specimens following neoadjuvant chemotherapy in advanced stage tubo-ovarian high-grade serous carcinoma. This prognostic biomarker has been included in ovarian cancer pathology reporting guidelines (International Collaboration on Cancer Reporting, College of American Pathologists) and in the upcoming European Society for Medical Oncology-European Society of Gynaecological Oncology (ESMO-ESGO) guidelines for ovarian cancer management. We present follow-up data on the CRS validation initiatives and suggest research with novel therapeutic agents incorporating this biomarker.MethodsThe cohort on whom CRS was originally developed was analyzed after an extended follow-up of an additional 36 months. The CRS histopathologic scoring system was applied to omental sections obtained at interval surgery from all 80 patients. Progression-free and overall survival were re-calculated.ResultsAfter a median follow-up of 4.3 years the CRS score predicted progression-free survival with an HR of 0.39 (95% CI 0.21 to 0.70), p = 0.002 adjusted for age, stage, and debulking status (median 1.08 vs 2.27 years for CRS1/2 vs CRS3). CRS was also predictive of overall survival with an HR of 0.17 (95% CI 0.07 to 0.44), p = 0.0002 adjusted for age, stage, and debulking status (median 2.55 vs 5.47 years for CRS1/2 vs CRS3).ConclusionCRS3 is a reproducible prognostic biomarker for improved progression-free and overall survival in stage 3C or 4 tubo-ovarian high-grade serous carcinoma after neoadjuvant chemotherapy. The score, obtained at interval debulking surgery, can help facilitate research and biomarker driven first-line treatment of patients with advanced ovarian cancer.

Key content Myocardial infarction is a rare but life-threatening medical condition during pregnancy. If unrecognised and not managed appropriately, the associated mortality and morbidity are high. A high index of suspicion, early diagnosis and treatment are essential. Multidisciplinary management involving the obstetric physician, cardiologist, anaesthetists and obstetrician is key to improving outcomes. Learning objectives To revise the physiological cardiovascular changes in pregnancy. To recognise the pathophysiology of myocardial infarction during pregnancy. Identify risks factors for myocardial infarction. Recognise symptoms and signs of myocardial infarction. To learn the general management principles of myocardial infarction in pregnancy. Ethical issues Should asymptomatic pregnant women with multiple risk factors be screened for coronary heart disease?

Background Ovarian cancer is seventh most common cancer in women worldwide. Approximately 1.3% of women will be diagnosed with ovarian cancer at some point during their life time. The majority of tumours arise from surface of the ovary (epithelial). Two thirds of these women will present with advanced disease, requiring aggressive treatment, which includes debulking surgery (removal of as much disease as possible) and chemotherapy. However, most women (75%) with advanced epithelial ovarian cancer (EOC) will relapse following surgery and chemotherapy. Patients who relapse are treated with either platinum or non-platinum drugs and this is dependent on the platinum-sensitivity and platinum-free interval. These drug regimens are generally well-tolerated although there are potential severe side effects. New treatments that can be used to treat recurrence or prevent disease progression after first-line or subsequent chemotherapy are important, especially those with a low toxicity profile. Hormones such as luteinising hormone releasing hormone (LHRH) agonists have been used in the treatment of relapsed EOC. Some studies have shown objective remissions, while other studies have shown little or no benefit. Most small studies report a better side-effect profile for LHRH agonists when compared to standard chemotherapeutic agents used in EOC. Objectives To compare the effectiveness and safety of luteinising hormone releasing hormone (LHRH) agonists with chemotherapeutic agents or placebo in relapsed epithelial ovarian cancer (EOC). Search methods We searched the Cochrane Gynaecological Cancer Group trials register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase up to January 2016. We also searched registers of clinical trials and abstracts of scientific meetings. Selection criteria Randomised controlled trials (RCTs) that compared LHRH agonists with chemotherapeutic agents or placebo in relapsed EOC. Data collection and analysis Two review authors independently assessed whether relevant studies met the inclusion criteria, retrieved data and assessed risk of bias. Main results Two studies, including 97 women, met our inclusion criteria: one assessed LHRH agonist (leuprorelin) use in relapsed (platinum-resistant and platinum-refractory) EOC in comparison with a chemotherapeutic agent (treosulfan) (Du Bois 2002); the other examined LHRH agonist (decapeptyl) versus a placebo (Currie 1994). Since both studies had different control groups, a meta-analysis was not possible. There may be little or no difference between treatment with leuprorelin or treosulfan in overall survival (OS) (hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.58 to 1.67; very low-quality evidence) or progression-free survival (PFS) at six and 12 months (risk ratio (RR) 0.61, 95% CI 0.22 to 1.68, and RR 0.65, 95% CI 0.12 to 3.66; very low-quality evidence), respectively (Du Bois 2002). The duration of follow-up was 2.5 years and quality of life (QoL) was not reported in this study. Alopecia and fatigue were probably more common with treosulfan than leuprorelin (alopecia RR 0.32, 95% CI 0.12 to 0.91 (very low-quality evidence)). There may be little or no difference in other Grade 3/4 side effects: nausea and vomiting (RR 0.65, 95% CI 0.12 to 3.66 (very low-quality evidence)); neurotoxicity (RR 0.32, 95% CI 0.01 to 7.71 (very low-quality evidence)) and neutropenia (RR 0.97, 95% 0.06 to 14.97 (very low-quality evidence)), The Currie 1994 study, which compared decapeptyl treatment with placebo, reported mean PFS of 16 weeks verus 11.2 weeks, respectively. No relative effects measures or P value at a particular time point were reported. Overall survival (OS) and QoL outcomes were not reported. In addition, adverse events were only mentioned for the decapeptyl group. Adverse events were incompletely reported (no adverse events in decapeptyl group, but not reported for the placebo group). Authors' conclusions Based on this review of two small RCTs, there is not enough evidence to comment on the safety and effectiveness of LHRH agonists in the treatment of platinum-refractory and platinum-resistant (relapsed) EOC. Overall, the quality of evidence for all outcomes (including OS, PFS, QoL and adverse events) is very low.

Key content • Uterine rupture is an uncommon complication of pregnancy associated with potentially catastrophic consequences for both mother and baby. • Previous uterine surgery is the most common underlying cause; however, multiparous women without uterine scarring are also at risk if labour becomes obstructed. • A review of CEMACH reports has shown a consistent decrease in maternal mortality secondary to uterine rupture despite increasing caesarean section rates. • The risk of uterine rupture during attempted vaginal birth after caesarean section is widely recognised; however, there needs to be greater awareness of this emergency occurring in multiparous women undergoing induction/augmentation of labour. Learning objectives • To define uterine rupture. • To examine the causes and risk factors for antepartum and intrapartum uterine rupture. • To review the signs and symptoms. • To revise the management of uterine rupture. • To increase awareness of this very serious complication and to suggest how clinicians can make a case-based individual assessment of uterine rupture risk. Ethical issues • Are those women at risk of uterine rupture adequately counselled about the possibility and potential consequences? Please cite this article as: Manoharan M, Wuntakal R, Erskine K. Uterine rupture: a revisit The Obstetrician & Gynaecologist 2010;12:223–230.

Obesity is a modern day epidemic. The incidence appears to be rapidly increasing in both developed and developing countries and has become much more obvious in the last decade. It is regarded as one of the major risk factors in pregnant women and has particularly gained recognition in obstetric practice due to its potentially adverse effects on pregnancy and the fetus. There is evidence to show that obesity in pregnancy contributes to increased morbidity and mortality in both mother and baby. It is associated with adverse outcomes such as preeclampsia, gestational diabetes, thromboembolism, fetal abnormalities and large for gestational infants. According to the Confidential Enquiries into Maternal Deaths in the United Kingdom, 35% of the women who died had a BMI of 30 or more. All these issues highlight the immense importance in treating women with obesity in maternity practice accordingly.

• Acute uterine inversion is a rare and unpredictable obstetric emergency. • Mortality and morbidity are reduced by early recognition and management. • Shock and uterine replacement must be addressed simultaneously. • The importance of teamwork cannot be overemphasised. • There is a need for skills and drills training because of the rarity of acute inversion. Learning objectives: • To understand the pathophysiology. • To understand and to be able to evaluate critically the general management principles. Ethical issues: • Management of uterine inversion is guided by a relatively small evidence base, resulting in treatment modalities being used without proper evaluation. Please cite this article as: Bhalla R, Wuntakal R, Odejinmi F, Khan RU. Acute inversion of the uterus. The Obstetrician & Gynaecologist 2009;11:13–18.

ObjectiveThe aims of this study were to assess locality of the sentinel lymph node (SLN) in cervical carcinoma and examine factors affecting bilateral SLN detection.MethodsThis was a retrospective review of SLN data (anatomical location, count and laterality) in patients with early-stage cervical cancer (International Federation of Gynecology and Obstetrics stage IA1 with lymphovascular space invasion to stage IIA) using intraoperative gamma probe and blue dye. The preoperative single-photon emission computed tomography with computed tomography was used to detect laterality, number of the SLNs, and rare locations. Patients were treated between January 2005 to January 2015 at the West Kent Gynaecological Oncology Centre, Maidstone Hospital, Maidstone, United Kingdom.ResultsA total of 132 women were investigated. The most common SLN location was the external iliac (38.6%) followed by obturator (25.3%) and internal iliac (23.6%) regions. A small percentage was identified in presacral (1.4%) and para-aortic regions (0.7%). Older age (P= 0.01) and an elevated body mass index (P= 0.03) were associated with decreased SLN count by preoperative single-photon emission computed tomography with computed tomography, and only age affected SLN count by gamma probe (P= 0.01). Initial surgery, large loop excision of the transformation zone, or cone biopsy of the cervix had no effect on SLN count. There was no difference observed in bilateral detection with respect to surgical approach (open: n = 48/laparoscopic: n = 84). However, older age was independently associated with a decrease in bilateral SLN detection (P= 0.003). In these patients who underwent unilateral full pelvic lymphadenectomy, all the nonsentinel nodes were negative.ConclusionsThe majority of SLNs were located in the external iliac, obturator, and internal iliac regions. Both older age and an elevated body mass index were associated with a reduced SLN count. Unilateral detection of SLN was independently associated with older age, which may be due to sclerosis in the lymphatic vessels or reduced perfusion in the pelvis in these women. If no SLN is detected on one side, the consensus is to perform a full pelvic lymphadenectomy on that side of the pelvis.

Changes in metabolism, hormone profile and blood circulation that normally occur during pregnancy can affect functioning of the mother's eyes.Visual changes in pregnancy are common and many are specifically associated with pregnancy itself. Knowledge of these ocular changes can help to differentiate the physiological changes from ocular manifestation of systemic disease and diseases pertaining to the eye in a pregnant woman. The effects of pregnancy on the eye are reviewed in this article.

Damage to the lower ureters during pelvic surgery is a serious and well-recognized complication. In most series, ureteric injury occurred in 0.5%-1.0% of all pelvic operations. The incidence of ureteric injuries is high with extensive abdominal operations for carcinoma of cervix (1.5%-2.5%) more so with patients who had preoperative radiotherapy. We treated 34 women with iatrogenic ureteric injuries during a 20-year period following radical hysterectomy for carcinoma cervix. The time of recognition of injury in 25 cases was during primary surgery and treated immediately. Surgery was uneventful in 9 patients of whom 7 presented in the early postoperative period and 2 during follow-up. These patients were managed by ureteroneocystostomy, percutaneous nephrostomy (PCN), and double J (DJ) stenting. All the renal units were salvaged. Immediate ureteric repair is advocated for all injuries discovered intraoperatively. Action to prevent the development of iatrogenic ureteral injury must be taken in advance, and ...