Endometrial Cancer: Analysing Patterns of Recurrence and Real-Life Outcome Data Using the 2020 ESGO-ESTRO-ESP Risk Stratification System.

AIMS: To evaluate patterns of recurrence and explore the prognostic differences between the 2018 FIGO staging system and the 2020 ESGO-ESTRO-ESP risk stratification system of endometrial cancer with an emphasis on early-stage disease. BACKGROUND: The incidence of endometrial cancer has risen by around 60% since the 90's. It is projected that by 2035 endometrial cancer will be the sixth most common cause of cancer-related death amongst females. METHODS: This was a retrospective cohort study which included patients treated between 2010 and 2017. Primary endpoints were overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meyer survival analysis was used to assess OS and RFS across different risk groups. Cox proportional hazards regression was used to evaluate prognostic risk factors implicated in recurrence. Different recurrence patterns across the subgroups were analysed with Pearson's chi-square test. RESULTS: The study included 692 patients with a recurrence rate of 14.9%. The median time to recurrence was 17.1 months (IQR:8.8-28.4). The mean OS varied between 97.2 months in the low-risk group to 63.1 months in the high-risk group (p < 0.001). Mean RFS was 96.1 in the low-risk group and 58.9 in the high-risk group (p < 0.001). RFS was predicted by the following factors; high risk group (OR=3.87; p = 0.041), LVSI (OR=2.54, p = 0.005), carcinosarcoma (OR=2.20, p = 0.021) and serous subtype (OR=1.91, p = 0.01). Logistic regression was used to evaluate risk factors for loco-regional and distant recurrence. Patients in the low-risk group were less likely to have distant recurrence (OR=0.08, p = 0.004). Similarly, negative LVSI and Grade 1 cancers were associated with decreased risk of distant recurrence (OR=0.34, p = 0.006 and OR=0.33, p = 0.007, respectively). There were no significant risk factors for loco-regional recurrence. CONCLUSIONS: The 2020 ESGO-ESTRO-ESP risk stratification provides accurate estimates of recurrence risk and survival. Those treated in line with current guidance have significantly better outcomes.

Personal professional indemnity and contractual issues for trainees in obstetrics and gynaecology.

Over the last few decades, more healthcare professionals have faced investigation into complaints about medical care and healthcare outcomes (Department of Health 2003). With increasing medical negligence cases being brought against doctors, it is time to carefully consider the implications of such actions to ensure appropriate safeguards (Ferner and McDowell 2006). At a time when the culture of 'no win, no fee' is rampant, the jobbing frontline doctor is on the back-foot trying to untangle the legalities of a malpractice claim (Ferner and McDowell 2006). Reassuringly, the numbers of doctors referred to the GMC or having to face legal procedures or claims for compensation are still very small (National Audit Office 2001). An essential issue for all doctors is having appropriate indemnity cover in the event that their practice is challenged. The opt-out for the European Working Time Regulations (EWTR) has caused further confusion as to what is covered for junior doctors by individual indemnity policies and the employer's liability scheme. Recently, the RCOG Trainees committee and the BMA Junior Doctors Association issued a joint advice regarding this issue (RCOG 2010). In this paper, we consider the differences in cover provided by the employer's liability scheme, individual professional indemnity schemes and the role of professional bodies. We also seek to clarify the understanding of these surrounding EWTR and the voluntary opt-out clause and provide up-to-date information on medico-legal issues and protection schemes regarding legal liabilities.

Training the trainees: an evaluation exercise using the TLH and BSO model.

Our aim was to evaluate surgical training in gynaecological oncology by assessing the time required by a trainee to complete a single laparoscopic gynaecologic-oncological operation. A total of 135 patients with a BMI < 40 kg/m2, diagnosed with endometrial cancer, underwent a total laparoscopic hysterectomy and bilateral salpingo-oophorectomy (TLH and BSO). Patients in Group I (n = 78) were operated on by a consultant gynaecological oncology surgeon and in Group II (n = 57) by sub-specialist trainees (SSTs). The mean patient age and BMI was 63.5 years and 29.6 kg/m2, respectively, in Group I and 64.5 years and 29.9 kg/m2, respectively, in Group II. Median operating times for Groups I and II were 58 and 90 min, respectively (p < 0.05). Furthermore, significant improvement was noted when comparing the average operating time between the first and second half of SST training. Even experienced gynaecological trainees take significantly longer to perform a reproducible laparoscopic operation. At the completion of training, an SST demonstrates improvement with respect to operation duration but is still not as fast as the trainer.

The role of cytology and other prognostic factors in endometrial cancer.

The clinical and prognostic value of positive cytology in women with endometrial cancer remains uncertain. The aim of our retrospective observational study was to determine whether in women with disease confined to the uterus, positive peritoneal cytology adversely affects disease-free (DFS) or overall survival (OS); to assess whether positive or negative cytology affects survival in women irrespective of stage and to assess whether the use of hysteroscopy or Pipelle for diagnosis affected cytology positivity rates. We have shown that median DFS and OS were almost identical for tumours confined to the uterus with and without positive peritoneal cytology. Women with tumours extending to the serosa or adnexa had a non-statistically significant shorter survival in comparison with women with stage I disease and negative cytology. Out of 59 women that had their cancer diagnosis based on a Pipelle biopsy of the endometrium, five had positive peritoneal washings. A total of 150 women had pre-treatment hysteroscopy; seven of these had positive peritoneal washings. There was no significant difference in the rates of positive cytology between these groups (4.6% vs 8.4%). In our cohort of un-staged women, positive peritoneal cytology did not adversely affect prognosis when disease was confined to the uterus.

Collaboration between the military and a charity: delivering care to patients, training to defence medical staff and defence engagement overseas.

The Royal College of Anaesthetists Military Anaesthesia higher training module was approved in 2008. The opportunities for trainee deployments to operational environments are limited, and while the need to ensure training and demonstrate the unique military skill set remains, these may not be consistently attainable within NHS posts. This paper proposes a template for the successful integration of military training with a charity mission by describing experiences in Addis Ababa over the two weeks of Project Harar's 2020 Complex Surgery Mission. This model not only benefits patients and military trainees by providing opportunities to gain the skills and attributes required by the Armed Services Consultant Appointment Board, but also by projecting the Defence Medical Services on the global stage.

Microtrap electrode devices for single cell trapping and impedance measurement.

This paper reports the design and fabrication of electrode microtraps for single cell trapping and impedance measurement. In this work, the microtrap electrodes of parallel and elliptical geometry have been fabricated by electroplating of gold electrodes of optimum thickness. This has enabled the formation of electrode traps without requiring any precision alignment between separate insulating traps like PDMS and the bottom gold electrodes. Further the improved uniformity of the electric field between the trapping electrodes as observed from COVENTORWARE simulation significantly reduces the effect of cell position inside the microwell on the electrical measurement unlike previous reports. This makes it possible to directly extract the equivalent cell parameters from the electrical measurement without introducing any correction factor corresponding to cell position. We have performed impedance spectroscopy with both the microwell electrode structures with single HeLa cell at two different positions of trapping. It has been observed that there is almost no change in the extracted values of cell resistance and capacitance for different positions within parallel electrodes and there is only 0.7 % and 0.85 % change in cell resistance and capacitance for the two positions within elliptical electrodes. Thus these microwell electrode structures can be used as an improved and a more convenient platform for single cell electrical characterization.

Abdominal radical trachelectomy in West London.

OBJECTIVE: Traditionally, the surgical management of invasive cervical carcinoma that has progressed beyond microinvasion has been a radical abdominal hysterectomy. However, this results in the loss of fertility, with significant consequences for the young patient. This report describes abdominal radical trachelectomy (ART) as a potential replacement for radical hysterectomy in patients with stage IA2-IIA cervical cancer who desire a fertility-sparing procedure without decreasing the curative rates. DESIGN: Observational, retrospective study. SETTING: Teaching hospital and regional cancer centre in London, UK. POPULATION: Patients undergoing ART. METHODS: Patients presenting during the period 2000-2009 with cervical cancer stage IA2-IIA were offered a trachelectomy, if they expressed a desire to preserve fertility. The type of trachelectomy (vaginal/abdominal) was chosen based on patient anatomy and neoplastic and magnetic resonance imaging characteristics. Each patient was counselled as to the experimental nature of the procedure. MAIN OUTCOME MEASURES: Survival, recurrence and fertility issues among ART patients. RESULTS: A total of 30 patients underwent ART (open and laparoscopic) between 2001 and 2009. Three patients presented with a recurrence, two of which have died (median follow-up: 24 months). Only three patients required further surgical re-intervention because of operative complications. Ten patients attempted to conceive, resulting in three conceptions (30%) and two live children. CONCLUSIONS: Abdominal radical trachelectomy provides a feasible, cost-effective and safe treatment option for young women who have been diagnosed with early-stage cervical cancer and wish to preserve their fertility.

Total laparoscopic hysterectomy for early stage endometrial cancer in obese and morbidly obese women.

This is a retrospective observational study, where we have evaluated the role of total laparoscopic hysterectomy (TLH) in obese and morbidly obese patients with early stage endometrial cancer. Our study illustrates that low conversion rates are achievable when appropriately trained surgeons undertake this procedure. All the women with high BMI were operated on laparoscopically in preference to laparotomy, unless there was an obvious contraindication such as a very large uterus or disseminated disease. We have also shown low conversation and complication rates for our patients, in particular a low rate of wound infection. This is in contrast to the high rate of wound infection and prolonged hospital stay reported for obese patients in the literature. Our study shows that TLH for endometrial cancer in obese women is feasible, safe and is likely to be cost-effective and adds to the weight of evidence for its use in this condition.

Laparoscopic and Robotic Surgery for Endometrial and Cervical Cancer.

Minimally invasive surgery (MIS) has many benefits, in the form of reduced postoperative morbidity, improved recovery and reduced inpatient stay. It is imperative, however, when new techniques are adopted, in the context of treating oncology patients, that the oncological efficacy and safety are established rigorously rather than assumed based on first principles. Here we have attempted to provide a comprehensive review of all the contentious and topical themes surrounding the use of MIS in the treatment of endometrial and cervix cancer following a thorough review of the literature. On the topic of endometrial cancer, we cover the role of laparoscopy in both early and advanced disease, together with the role and unique benefits of robotic surgery. The surgical challenge of patients with a raised body mass index and the frail and elderly are discussed and finally the role of sentinel lymph node assessment. For cervical cancer, the role of MIS for staging and primary treatment is covered, together with the interesting and highly specialist topics of fertility-sparing treatment, ovarian transposition and the live birth rate associated with this. We end with a discussion on the evidence surrounding the role of adjuvant hysterectomy following radical chemoradiation and pelvic exenteration for recurrent cervical cancer. MIS is the standard of care for endometrial cancer. The future of MIS for cervix cancer, however, remains uncertain. Current recommendations, based on the available evidence, are that the open approach should be considered the gold standard for the surgical management of early cervical cancer and that MIS should only be adopted in the context of research. Careful counselling of patients on the current evidence, discussing in detail the risks and benefits to enable them to make an informed choice, remains paramount.

An electron holography study of perpendicular magnetic tunnel junctions nanostructured by deposition on pre-patterned conducting pillars.

The fabrication of multi-gigabit magnetic random access memory (MRAM) chips requires the patterning of magnetic tunnel junctions at very small dimensions (sub-30 nm) and a very dense pitch. This remains a challenge due to the difficulty in etching magnetic tunnel junction stacks. We previously proposed a strategy to circumvent this problem by depositing the magnetic tunnel junction material on prepatterned metallic pillars, resulting in the junction being naturally shaped during deposition. Upon electrical contact, the deposit on top of the pillars constitutes the magnetic storage element of the memory cell. However, in this process, the magnetic material is also deposited in the trenches between the pillars that might affect the memory cell behaviour. Here we study the magnetic interactions between the deposit on top of the pillars and in the trenches by electron holography, at room temperature and up to 325 °C. Supported by models, we show that the additional material in the trenches is not perturbing the working principle of the memory chip and can even play the role of a flux absorber which reduces the crosstalk between neighboring dots. Besides, in the studied sample, the magnetization of the 1.4 nm thick storage layer of the dots is found to switch from out-of-plane to an in-plane configuration above 125 °C, but gradually decreases with temperature. Electron holography is shown to constitute a very efficient tool for characterizing the micromagnetic configuration of the storage layer in MRAM cells.

Effect of postoperative radiotherapy on autologous deep inferior epigastric perforator flap volume after immediate breast reconstruction.

BACKGROUND: The effect of postoperative radiotherapy following autologous flap breast reconstruction is controversial. The aim of this study was to measure whether adjuvant radiotherapy following immediate deep inferior epigastric perforator (DIEP) free flap breast reconstruction affected flap volume. METHODS: Sixty-eight women underwent immediate autologous DIEP flap reconstruction following mastectomy for breast cancer. Twenty-two of the 68 received postoperative radiotherapy (45Gy in 20 fractions over 4 weeks). Intraoperative flap volume data were collected prospectively. Volumetric assessment was carried out a minimum of 1 year after surgery. Patients who had volume adjustment surgery after initial reconstruction were analysed separately. RESULTS: The mean age of the women was 52 (range 37-69) years and median follow-up was 3.5 (range 1-10) years. There was no statistically significant difference in volume change between patients who had and those who did not have postreconstruction radiotherapy for the whole cohort (median reduction 65 versus 0 ml) or when women who had undergone further volume adjustment surgery were excluded. CONCLUSION: In this study postoperative radiotherapy did not significantly affect breast volume after DIEP flap reconstruction. The potential need for postoperative radiotherapy should not deter women from undergoing immediate DIEP flap breast reconstruction.

The Role of Biomarkers for the Prediction of Response to Checkpoint Immunotherapy and the Rationale for the Use of Checkpoint Immunotherapy in Cervical Cancer.

Checkpoint immunotherapy has revolutionised the way that melanoma is treated and has also shown significant effectiveness in lung, bladder, renal, and head and neck cancers. At the present time, trials of checkpoint immunotherapy in cervical cancer are at early phases, but there is very good rationale for pursuing this as a treatment option, especially as cervical cancer is a virally driven cancer and therefore should be recognised by the immune system as being foreign. This review explores the biomarkers for the selection of patients for immunotherapy in other cancers, such as programmed death ligand 1 (PD-L1) expression, tumour infiltrating lymphocytes and total mutational burden, and relates these biomarkers to cervical cancer. A PubMed search was carried out for publications published in English with the terms 'immunotherapy' OR 'cervical cancer' OR 'checkpoint blockade' OR 'tumour infiltrating lymphocytes' OR 'total mutational burden'. Articles that met these criteria and were available on PubMed before 8 October 2018 were included. The results showed that PD-L1 is positive in up to 90% of cervical cancers and that the total mutational burden is moderately high, with 5-6 mutations per megabase. In addition, the tumour microenvironment in cervical cancer has an impact on prognosis, with higher ratios of CD8+ tumour infiltrating lymphocytes to CD4+ T regulatory cells being associated with improved survival. Clinical studies to date have shown the response rate of cervical cancer to checkpoint immunotherapy to be in the region to 10-25%. Cervical cancer exhibits many of the features that have been shown to be correlated with response to checkpoint immunotherapy in other tumour sites. However, response rates to date are in the region of 10-25%. Therefore, combinations of immunotherapeutic agents or checkpoint inhibitors with radiotherapy may be required to maximise the therapeutic benefit of harnessing the host immune system to fight cancer.

The Human Papillomavirus as a Common Pathogen in Oropharyngeal, Anal and Cervical Cancers.

The burden of human papillomavirus (HPV)-related cancers worldwide is significant. Although the incidence of cervical cancer is decreasing due to cervical screening programmes, the incidences of oropharyngeal, anal and vulval cancers are increasing. The introduction of HPV vaccination programmes in many countries has had an impact on HPV infection rates but due to the time-lag from initial HPV infection to the development of invasive carcinoma, the impact on the incidence of HPV-related cancer will take more time to become evident. This review explores the common aspects of HPV-related cancers and how they differ from their HPV-negative counterparts, both clinically and molecularly. It also covers the implications this has on future treatment strategies, including the possible role of immunotherapy.

EDXRF analysis of municipal solid waste using (109)Cd source.

Elemental compositions of municipal solid waste (MSW) samples have been analyzed using the non-destructive energy dispersive X-ray fluorescence (EDXRF) technique. The samples were collected from three different dumping sites of urban and suburban areas of the city of Kolkata, West Bengal, India. The EDXRF spectrometer consisted of a (109)Cd radioactive source and a Si (Li) detector. To check the reliability of the system, NIST Standard Reference Material-1648 UPM had been analyzed and it was found that within the experimental errors, our results agree quite well with the certified and non-certified values. The elemental compositions of all the three MSW samples were subsequently estimated using the same procedure. The matrix effects were estimated following the emission-transmission method. It was observed that except Fe, all the elements from Ti to Pb show concentration levels higher by a factor of 2-7 than the ecological screening values where as in the case of Fe, this factor varies from 100 to 200.

Congenital nodular multiple glomangioma: a case report.

A 13 year old girl presented with recurrent painful "varicosities" on her right calf. These lesions were subsequently clinically diagnosed as "cavernous haemangiomas" after normal duplex scanning and were excised. Histological examination revealed multiple glomangiomas (glomus tumours). A literature review revealed only two reported cases of nodular multiple glomangioma, so that this is the third case to be reported in the literature.