Identifying the Optimum Strategy for Identifying Adults and Children With Celiac Disease: A Cost-Effectiveness and Value of Information Analysis.

OBJECTIVES: Celiac disease (CD) is thought to affect around 1% of people in the United Kingdom, but only approximately 30% are diagnosed. The aim of this work was to assess the cost-effectiveness of strategies for identifying adults and children with CD in terms of who to test and which tests to use. METHODS: A decision tree and Markov model were used to describe testing strategies and model long-term consequences of CD. The analysis compared a selection of pre-test probabilities of CD above which patients should be screened, as well as the use of different serological tests, with or without genetic testing. Value of information analysis was used to prioritize parameters for future research. RESULTS: Using serological testing alone in adults, immunoglobulin A (IgA) tissue transglutaminase (tTG) at a 1% pre-test probability (equivalent to population screening) was most cost-effective. If combining serological testing with genetic testing, human leukocyte antigen combined with IgA tTG at a 5% pre-test probability was most cost-effective. In children, the most cost-effective strategy was a 10% pre-test probability with human leukocyte antigen plus IgA tTG. Value of information analysis highlighted the probability of late diagnosis of CD and the accuracy of serological tests as important parameters. The analysis also suggested prioritizing research in adult women over adult men or children. CONCLUSIONS: For adults, these cost-effectiveness results suggest UK National Screening Committee Criteria for population-based screening for CD should be explored. Substantial uncertainty in the results indicate a high value in conducting further research.

Alcohol's contribution to climate change and other environmental degradation: a call for research.

Climate change is the single biggest health threat facing humanity. The production, distribution and consumption of many fast-moving consumer goods contribute substantially to climate change, principally through releasing greenhouse gas emissions. Here we consider just some of the ways that alcohol-already a key contributor to an array of health, social and economic burdens-exacerbates environmental harms and climate change. We explore current evidence on alcohol production as a resource- and energy-intensive process, contributing to significant environmental degradation through water usage and other carbon emission costs. We argue that the impacts of alcohol production on climate change have been minimally explored by researchers. Yet the extent of the unfolding catastrophe beholds us to consider all available ways to mitigate unnecessary emissions, including from products such as alcohol. We then turn to suggestions for a research agenda on this topic, including investigations of commercial determinants, inequalities and product advice to help consumers choose lower-carbon options. We conclude by arguing that public health researchers already have an array of methodological expertise and experience that is well placed to produce the evidence needed to inform regulation and efforts by alcohol producers and consumers to minimize their contributions to environmental harms.

Knowledge, Beliefs, and Behaviors Related to Secondhand Smoke and Smoking in the Home: A Qualitative Study With Men in Malaysia.

INTRODUCTION: Despite the health risks associated with secondhand smoke (SHS) exposure, smoking in the home is common in Malaysia, and almost exclusively a male behavior. AIMS AND METHODS: This study explored male smokers' knowledge, beliefs, and behaviors related to SHS exposure and smoking in the home, to guide future intervention development. Twenty-four men who smoked and lived in Klang Valley, Kuantan, or Kuala Terengganu took part in semi-structured interviews which explored knowledge and beliefs regarding SHS in the home, and associated home-smoking behaviors. Data were managed and analyzed using the framework approach. RESULTS: There was limited knowledge regarding the health risks associated with SHS: the smell of SHS in the home was a more prominent concern in most cases. Many had no rules in place restricting home smoking, and some suggested that smoking in specific rooms and/or near windows meant SHS was not "shared" with other household members. A few fathers had created but not maintained a smoke-free home prior to and/or after their children were born. Desire to smoke in the home conflicted with men's sense of responsibility as the head of the household to protect others and set a good example for their children. CONCLUSIONS: Men's home-smoking behaviors are shaped by a lack of understanding of the health risks associated with SHS exposure. Gaining a broader understanding of the factors that shape men's decisions to create a smoke-free home is important to facilitate the development of culturally appropriate interventions that address their responsibility to protect other household members from SHS exposure. IMPLICATIONS: Our findings highlight the need for public information campaigns in Malaysia to educate men who smoke regarding the health harms associated with SHS in the home and the ways in which SHS travels and lingers in household air. This is important given men's concerns about SHS often focus on the smell of cigarette smoke in the home. Our findings suggest a number of potential avenues for future intervention development, including household and community-level initiatives that could build on men's sense of responsibility as the head of the household and/or their general desire to protect their families.

Exposure to secondhand and thirdhand smoke in private vehicles: Measurements in air and dust samples.

BACKGROUND: This study aimed to estimate airborne nicotine concentrations and nicotine, cotinine, and tobacco-specific nitrosamines (TSNAs) in settled dust from private cars in Spain and the UK. METHODS: We measured vapor-phase nicotine concentrations in a convenience sample of 45 private cars from Spain (N = 30) and the UK (N = 15) in 2017-2018. We recruited non-smoking drivers (n = 20), smoking drivers who do not smoke inside the car (n = 15), and smoking drivers who smoke inside (n = 10). Nicotine, cotinine, and three TSNAs (NNK, NNN, NNA) were also measured in settled dust in a random subsample (n = 20). We computed medians and interquartile ranges (IQR) of secondhand smoke (SHS) and thirdhand smoke (THS) compounds according to the drivers' profile. RESULTS: 24-h samples yielded median airborne nicotine concentrations below the limit of quantification (LOQ) (IQR:

Use of nicotine replacement therapy to reduce children's exposure to second-hand smoke in the home: a qualitative pilot study involving local community pharmacies.

BACKGROUND: In Scotland, and in several other countries, most second-hand smoke exposure now occurs in low-income households, where housing constraints and sole parenting often make it harder to create a smoke-free home. This pilot study provided people who smoke with a free 12-week supply of nicotine replacement therapy through local community pharmacies to reduce smoking indoors. METHODS: Twenty-five parents/caregivers who smoked in the home and cared for children at least weekly were recruited via Facebook during the COVID-19 pandemic. Air quality (PM2.5) was monitored in participant homes for seven days before their first pharmacy visit and 12 weeks later. Qualitative interviews (N = 14) were conducted with 13 participants who completed the study and one who withdrew part-way through. The interviews explored views/experiences of using nicotine replacement therapy to help create a smoke-free home. Another participant took part in a shorter telephone discussion at their request, with detailed notes taken by the interviewer, because of their speech disorder. RESULTS: Three participants reported smoking outdoors only, one of whom subsequently quit smoking. Six participants reported reduced cigarette consumption by 50% in the home, four reported no (sustained) reduction and one reported increased smoking indoors. Self-reported outcomes were not always consistent with PM2.5 readings. Participants' experiences of accessing nicotine replacement therapy through community pharmacies varied. Some suggested ongoing support to use nicotine replacement products could better assist behavioural change, and that access could be streamlined by posting products to the home. Several suggested that focusing on changing home smoking behaviours using nicotine replacement therapy might facilitate a future quit attempt. CONCLUSION: Access to free nicotine replacement therapy for temporary use indoors may support some people who smoke to reduce children's exposure to second-hand smoke. Our findings confirm the need to modify the intervention before undertaking a definitive trial to assess the effectiveness of this approach. This work is now underway.

Reasons for Using Roll-Your-Own Tobacco and Perceptions of Health-Promoting Pack Inserts: A Focus Group Study with Roll-Your-Own Tobacco Smokers in Scotland.

INTRODUCTION: Use of roll-your-own (RYO) tobacco is increasing in most regions, but few qualitative studies have explored why RYO smokers use this product, and no study has considered their views of health-promoting pack inserts. METHODS: Eight focus groups were conducted with 18-35-year-old RYO smokers (n = 50) in Greater Glasgow (Scotland) in February-March 2020 to explore reasons for using RYO and perceptions of health-promoting inserts. Participants were shown four inserts adapted from those required in cigarette packs in Canada, with all encouraging quitting, and two RYO-specific inserts explaining that RYO is not less harmful than cigarettes. RESULTS: Lower price, better taste, the pleasure of rolling and ability to customize roll-ups, and the belief that RYO was less harmful than cigarettes were drivers for use. There were mixed perceptions of the extent to which inserts would capture attention if included in RYO packs. The positive messaging used on the Canadian inserts was considered motivational and inspirational, and contrasted with the on-pack warnings. The messaging on the RYO inserts, in comparison, was viewed unfavorably and generally dismissed. Participants, most of whom were not interested in quitting, did not feel that inserts would lead them to change their smoking behavior. However, some felt that the Canadian inserts could be helpful for those thinking about quitting and young people contemplating smoking. CONCLUSIONS: Inserts with positive messaging about quitting, rather than messaging explicating the harms of RYO, were preferred by RYO smokers. What, if any, RYO-specific messaging resonates with RYO smokers merits further attention. IMPLICATIONS: Aside from price, taste, and the pleasure associated with rolling and ability to individualize roll-ups, the erroneous belief that RYO is less harmful than cigarettes was a key reason for use. While inserts with positive messaging about quitting, as used on the Canadian inserts, were viewed as potentially helpful, inserts that challenged the idea that RYO was not less harmful than cigarettes were generally dismissed. Research is needed to understand what types of RYO-specific messaging could most effectively be used on inserts, or indeed in other media, to challenge the misperceptions that many RYO smokers hold.

What Helps and What Hinders the Creation of a Smoke-free Home: A Qualitative Study of Fathers in Scotland.

INTRODUCTION: Few studies have explored fathers' views and experiences of creating a smoke-free home, with interventions largely targeting mothers. This study aimed to identify barriers and facilitators to fathers creating a smoke-free home, to inform future intervention development. METHODS: Eighteen fathers who were smokers and lived in Scotland were recruited from Dads' community groups, Early Years Centres and through social media advertising. Semi-structured interviews explored their views and experiences of creating a smoke-free home. A theory-informed thematic analysis using the COM-B model highlighted ways in which capability, opportunity, and motivations shaped fathers' home smoking behaviors. RESULTS: Several fathers understood the health risks of second-hand smoke exposure through public health messaging associated with recent smoke-free legislation prohibiting smoking in cars carrying children. Limited understanding of effective exposure reduction strategies and personal mental health challenges reduced some fathers' ability to create a smoke-free home. Fathers were keen to maintain their smoke-free home rules, and their motivations for this largely centered on their perceived role as protector of their children, and their desire to be a good role model. CONCLUSIONS: Fathers' abilities to create a smoke-free home are shaped by a range of capabilities, opportunities, and motivations, some of which relate to their role as a father. Establishing a fuller understanding of the contextual and gender-specific factors that shape fathers' views on smoking in the home will facilitate the development of interventions and initiatives that fathers can identify and engage with, for the broader benefit of families and to improve gender equity and health. IMPLICATIONS: Our findings can inform future development of father-centered and household-level smoke-free home interventions. They identify fathers' views and experiences and help reframe smoking in the home as a gendered family-wide issue, which is important in building consensus on how best to support parents to create a smoke-free home. Our findings highlight the need for additional research to develop understanding of the ways in which gender-related aspects of family structures, heterosexual relationships, and child living arrangements influence home smoking rules and how to tailor interventions accordingly.

FARGO-360: a multi-disciplinary survey of practice and perspectives on provision of care for patients with frailty presenting with gynecological cancers in the UK and Ireland.

OBJECTIVES: Frailty has been associated with worse cancer-related outcomes for people with gynecological cancers. However, the lack of clear guidance on how to assess and modify frailty prior to instigating active treatments has the potential to lead to large variations in practice and outcomes. This study aimed to evaluate current practice and perspectives of healthcare practitioners on the provision of care for patients with frailty and a gynecological cancer. METHODS: Data were collected via a questionnaire-based survey distributed by the Audit and Research in Gynecological Oncology (ARGO) collaborative to healthcare professionals who identified as working with patients with gynecological malignancies in the United Kingdom (UK) or Ireland. Study data were collected using REDCap software hosted at the University of Manchester. Responses were collected over a 16 week period between January and April 2021. RESULTS: A total of 206 healthcare professionals (30 anesthetists (14.6%), 30 pre-operative nurses (14.6%), 51 surgeons (24.8%), 34 cancer specialist nurses (16.5%), 21 medical/clinical oncologists (10.2%), 25 physiotherapists/occupational therapists (12.1%) and 15 dieticians (7.3%)) completed the survey. The respondents worked at 19 hospital trusts across the UK and Ireland. Frailty scoring was not routinely performed in 63% of care settings, yet the majority of practitioners reported modifying their practice when providing and deciding on care for patients with frailty. Only 16% of organizations surveyed had a dedicated pathway for assessment and management of patients with frailty. A total of 37% of respondents reported access to prehabilitation services, 79% to enhanced recovery, and 27% to community rehabilitation teams. CONCLUSION: Practitioners from all groups surveyed considered that appropriate training, dedicated pathways for optimization, frailty specific performance indicators and evidence that frailty scoring had an impact on clinical outcomes and patient experience could all help to improve care for frail patients.

'I'm killing myself, but I'm saving the planet': rolling tobacco smokers' perceptions of rolling papers.

INTRODUCTION: Despite the global growth of rolling tobacco, we are unaware of any research that has explored smokers' perceptions of the types of rolling papers available, or plain rolling papers, which are now required in Canada and Israel. METHODS: Eight focus groups were conducted with rolling tobacco smokers (n=50) in Greater Glasgow (Scotland) between February and March 2020. Participants were shown a number of packs of promotional rolling papers (natural, transparent, prerolled cones, flavoured) and plain rolling papers. RESULTS: Rolling papers were often viewed as functional, a necessity for making roll-ups. The appeal of papers was based on the packaging, with a booklet-style pack of natural papers viewed very positively, as well as novelty, usability and taste/smell. Participants often associated papers with particular users, with prerolled cones and some flavoured papers thought to be used by cannabis smokers or younger people and those just starting to smoke. In terms of harm perceptions, natural papers were viewed as a healthier choice than standard papers and more environmentally friendly, whereas transparent papers raised concerns about safety to both the user and the environment. Participants were generally ambivalent towards plain papers, which they did not feel would alter their purchasing or smoking behaviour, although some felt they may be less appealing to youth as the branding would be diminished. CONCLUSIONS: The panoply of rolling papers available offers consumers considerable choice. As some promotional papers can increase appeal or create misperceptions of harm then standardising papers would help to counter this.

Smoke-free spaces: a decade of progress, a need for more?

Adoption of smoke-free measures has been one of the central elements of tobacco control activity over the past 30 years. The past decade has seen an increasing number of countries and proportion of the global population covered by smoke-free policies to some extent. Despite reductions in global smoking prevalence, population growth means that the number of non-smokers exposed to the harms caused by secondhand smoke remains high. Smoke-free policy measures have been shown to be useful in protecting non-smokers from secondhand smoke, and can additionally increase cessation and reduce smoking initiation. Policies tend to be aimed primarily at enclosed public or workplace settings with very few countries attempting to control exposure in private or semiprivate spaces such as homes and cars, and, as a result, children may be benefiting less from smoke-free measures than adults. Compliance with legislation also varies by country and there is a need for education and empowerment together with guidance and changing social norms to help deliver the full benefits that smoke-free spaces can bring. Restrictions and policies on use of electronic cigarettes (e-cigarettes) in smoke-free settings require more research to determine the benefits and implications of bystanders' exposure to secondhand e-cigarette aerosol, dual use and smoking cessation.

Enteric Type Bartholin Gland Adenocarcinoma: An Unusual Variant of a Rare Neoplasm.

Vulval cancer is rare. With Bartholin gland carcinomas representing <5% of all vulval carcinomas they present both diagnostic and management challenges. There are a small number of cases in the literature describing Bartholin gland carcinomas with unusual histology which necessitates the need to explore the possibility of metastases from elsewhere. We present a case of a 55-yr-old woman presenting with a vulval lesion within the Bartholin gland. Morphology demonstrated enteric type adenocarcinoma and the immunohistochemistry profile was positive for CK7, CK20, CDX2, CEA, and CA19-9. There was no evidence of an alternative primary cancer and the tumor was excised with negative regional sentinel node assessment. Genotyping showed no detectable mutations in KRAS, BRAF or NRAS suggesting a possible future role for anti-EGFR therapy.

Initial Views and Experiences of Vaping in Prisons: A Qualitative Study With People in Custody Preparing for the Imminent Implementation of Scotland's Prison Smokefree Policy.

INTRODUCTION: Scotland is one of the few countries in which e-cigarettes were available in prisons before the introduction of a comprehensive national smokefree policy, to assist in its implementation. This qualitative study explores the initial views and experiences of vaping in this specific context, from the perspective of people in custody (prisoners). AIMS AND METHODS: Twenty-eight people in custody were interviewed approximately 1-2 months after rechargeable e-cigarettes were made available in prisons and 2-5 weeks before implementation of a smokefree policy. Data were thematically analyzed to identify the range and diversity of views and experiences. RESULTS: Participants expressed support for e-cigarettes in preparation for the smokefree policy, describing their symbolic and practical value in this context. Uptake of vaping was strongly influenced by the need for participants to manage without tobacco in the near future. Participants evaluated their initial vaping experiences, either positively or negatively, in relation to the utility of e-cigarettes for mandated smoking abstinence and in providing satisfaction, pleasure, and novelty. Participant views on several issues related to e-cigarette use, both specific to the prison population (product choice and cost) and more generally (safety and long-term use), are explored. CONCLUSIONS: Our findings suggest possible benefits of e-cigarettes as one means of supporting smokefree policy in a population with many smokers. They also point to potential challenges posed by vaping in prisons and smokefree settings caring for similar populations. There is a need for ongoing measures to maximize the health benefits of smokefree settings and for further research on vaping in situations of enforced abstinence. IMPLICATIONS: To our knowledge, no published studies have explored views and experiences of vaping in prison, when rechargeable vapes were new and the removal of tobacco was imminent. The results can inform tobacco control policy choices, planning and implementation in prisons and similar settings. In prison systems that permitting vaping, it is important that other measures (eg, information campaigns and nicotine dependence services) are implemented concurrently to minimize potential risks to the health or personal finances of people in custody.

E-cigarette Use in Prisons With Recently Established Smokefree Policies: A Qualitative Interview Study With People in Custody in Scotland.

INTRODUCTION: E-cigarettes were one measure introduced to help people in custody (PiC) to prepare for and cope with implementation of comprehensive smokefree policies in Scottish prisons. Our earlier study explored experiences of vaping when e-cigarettes were first introduced and most participants were dual tobacco and e-cigarette users. Here we present findings of a subsequent study of vaping among a different sample of PiC when use of tobacco was prohibited in prison, and smokefree policy had become the norm. METHODS: Twenty-eight qualitative interviews were conducted with PiC who were current or former users of e-cigarettes in prison, 6-10 months after implementation of a smokefree policy. Data were managed and analyzed using the framework approach. RESULTS: PiC reported that vaping helped with mandated smoking abstinence. However, findings suggest that some PiC may be susceptible to heavy e-cigarette use potentially as a consequence of high nicotine dependence and situational factors such as e-cigarette product choice and availability in prisons; issues with nicotine delivery; prison regimes; and use of e-cigarettes for managing negative emotions. These factors may act as barriers to cutting down or stopping use of e-cigarettes by PiC who want to make changes due to dissatisfaction with vaping or lack of interest in continued use of nicotine, cost, and/or health concerns. CONCLUSIONS: E-cigarettes helped PiC to cope with smokefree rules, although concerns about e-cigarette efficacy, cost, and safety were raised. PiC may desire or benefit both from conventional smoking cessation programs and from interventions to support reduction, or cessation, of vaping. IMPLICATIONS: Findings highlight successes, challenges, and potential solutions in respect of use of e-cigarettes to cope with mandated smoking abstinence in populations with high smoking prevalence and heavy nicotine dependence. Experiences from prisons in Scotland may be of particular interest to health and/or justice services in other jurisdictions, with similar legislation on e-cigarettes to the United Kingdom, who are planning for institutional smokefree policies in their prisons or inpatient mental health settings in the future.

BRAF Wild-type, PTEN Mutant Malignant Uveal Melanoma Arising Within a Mature Ovarian Teratoma: A Case Report and Review of the Literature.

Mature cystic teratomas are common in women of all ages; however, malignant transformation within them is rare and difficult to diagnosis preoperatively. Primary melanoma of the ovary is exceptionally rare and only occurs in relation to a teratoma where it can originate from sporadic somatic mutagenesis within epidermal junctional melanocytes, through malignant transformation of a benign nevus formed within the mature cystic teratoma or from other well differentiated pigment-containing structures such as the uvea. We present a case of primary malignant melanoma arising within a mature cystic teratoma in a young patient, who ultimately developed widespread metastasis necessitating systemic therapy. Our case highlights the role of molecular medicine not only in forming an understanding the origin of the melanoma, but also guiding targeted systemic therapies. Alongside the case we present a review of the literature describing the incidence of molecular aberrations within melanoma as well as the established and emerging techniques and cytotoxic agents for malignant melanoma.

Post-operative pancreatic fistula following splenectomy with or without distal pancreatectomy at cytoreductive surgery in advanced ovarian cancer.

OBJECTIVE: Splenectomy with or without distal pancreatectomy may be necessary at time of cytoreductive surgery to achieve complete cytoreduction in advanced ovarian cancer. However, these procedures have been associated with peri-operative morbidity. The aims of this study were to determine the incidence of distal pancreatectomy among patients undergoing splenectomy during cytoreductive surgery for advanced ovarian cancer and to determine the incidence, management, treatment, and prognosis of patients with post-operative pancreatic fistula. METHODS: Retrospective cohort study of all consecutive patients with FIGO stage IIIC-IVB ovarian, fallopian tube, or primary peritoneal cancer who underwent splenectomy with or without distal pancreatectomy, during primary, interval, or secondary cytoreductive surgery between January 2007 and December 2017. All histologic subtypes were included; patients with borderline ovarian tumor and those undergoing emergency surgery were excluded from analysis. Univariate analyses for survival were generated by Kaplan-Meier survival curves and log-rank (Mantel-Cox) tests for statistical significance. Patients who underwent surgery for recurrence were excluded from survival analysis. Inter-group statistics were performed using Student's t-test for continuous variables, and chi-square test and Fisher's exact test for categorical variables. RESULTS: A total of 156/804 (19.4%) women underwent splenectomy, and of these 22 (14.1%) patients had distal pancreatectomy. Of patients who underwent splenectomy only, 2/134 (1.5%) developed grade B post-operative pancreatic fistula and 6/22 (27.3%) patients who underwent distal pancreatectomy developed grade B and C post-operative pancreatic fistula. Five (83.3%) of six of these patients were symptomatic. Distal pancreatectomy patients had a higher risk of developing post-operative pancreatic fistula when compared with patients who underwent splenectomy only (63.7% vs 9.7%, p=0.0001). Median length of hospital stay was longer in patients with post-operative pancreatic fistula: 16.5 (range 7-38) days compared with 10 (range 7-15) days (p=0.019). There was no progression-free survival (p=0.42) and disease-specific survival (p=0.33) difference between patients undergoing splenectomy with or without distal pancreatectomy. CONCLUSION: Clinically relevant post-operative pancreatic fistula is a relatively frequent complication (27.3%) following distal pancreatectomy and it is a possible complication after splenectomy only (1.5%).

Extending health messaging to the consumption experience: a focus group study exploring smokers' perceptions of health warnings on cigarettes.

Introduction: While most countries require health warnings on cigarette packs, the Scottish and Canadian Governments are considering requiring health warnings on cigarette sticks. Methods: Twenty focus groups were conducted in Glasgow and Edinburgh (Scotland) with smokers (n = 120) segmented by age (16-17, 18-24, 25-35, 36-50, >50), gender and social grade, to explore perceptions of cigarettes displaying the warning 'Smoking kills' on the cigarette paper and any demographic differences in how smokers responded to these. Results: A warning on each cigarette was thought to prolong the health message, as it would be visible when a cigarette was taken from a pack, lit, left in an ashtray, and with each draw, and make avoidant behavior more difficult. That it would be visible to others was perceived as off-putting for some. It was felt that a warning on each cigarette would create a negative image and be embarrassing. Within several female groups they were viewed as depressing, worrying and frightening, with it suggested that people would not feel good smoking cigarettes displaying a warning. Within every group there was mention of warnings on cigarettes potentially having an impact on themselves, others or both. Some, mostly younger groups, mentioned stubbing cigarettes out early, reducing consumption or quitting. The consensus was that they would be off-putting for young people, nonsmokers and those starting to smoke. Conclusions: Including a warning on each cigarette stick is a viable policy option and one which would, for the first time, extend health messaging to the consumption experience.

Borderline Ovarian Tumors: Fifteen Years' Experience at a Scottish Tertiary Cancer Center.

OBJECTIVES: Since the recognition of borderline ovarian tumors (BOTs) in the 1970s, the management of this subset of epithelial ovarian tumors has presented a challenge to clinicians. The majority present at an early stage, but their diagnosis is often only made following surgery, hence the heterogeneity of surgical management. Borderline ovarian tumors are morphologically diverse, and their behavior is subsequently also heterogeneous. We aimed to assess recurrence rates and the rate of malignant transformation in patients diagnosed with BOT. Secondary objectives included a review of current management and assessment of tumor markers, stage, cyst dimensions, and the presence of micropapillary features as prognostic indicators of recurrence. METHODS: This retrospective cohort study included all patients treated with BOT between 2000 and 2015 in the southeast region of Scotland. Clinical, surgicopathological, and follow-up data were collated. Data were analyzed with reference to recurrence and malignant transformation. RESULTS: Two hundred seventy-five patients underwent treatment for BOT in the study period. Surgical management was highly variable. A diagnosis of recurrent/persistent BOT or ovarian malignancy following initial treatment of BOT was rare, with only 12 (4%) of 275 cases. There were 7 cases (3%) of ovarian malignancy. Advanced International Federation of Gynecology and Obstetrics stage was the most prominent prognostic factor. Elevated preoperative serum CA-125 and the presence of micropapillary features correlated with advanced stage at presentation. With a lack of clear guidance, follow-up was highly variable with a median of 43 months (0-136 months). CONCLUSIONS: To our knowledge, this study is the largest BOT cohort in the United Kingdom. Recurrent disease is rare in optimally staged, completely resected, early-stage BOT, without high-risk features. Caution is needed in women electing not to undergo completion staging after diagnosis and in those opting for a fertility-preserving approach. Thorough informed consent and clear plans for surveillance and follow-up are needed with consideration of delayed completion surgery as appropriate.

Locally advanced vulva cancer: A single centre review of anovulvectomy and a systematic review of surgical, chemotherapy and radiotherapy alternatives. Is an international collaborative RCT destined for the "too difficult to do" box?

INTRODUCTION: Treatment of locally advanced vulva cancer (LAVC) remains challenging. Due to the lack of randomised trials many questions regarding the indications for different treatment options and their efficacy remain unanswered. METHODS: In this retrospective study we provide the largest published series of LAVC patients treated with anovulvectomy, reporting oncological outcomes and morbidity. Additionally, a systematic literature review was performed for all treatment options 1946-2015. RESULTS: In our case series, 57/70 (81%) patients were treated in the primary setting with anovulvectomy and 13 patients underwent anovulvectomy for recurrent disease. The median overall survival (OS) was 69months (1-336) with disease specific survival of 159months (1-336). Following anovulvectomy for primary disease, time to progression and OS were significantly higher in node negative disease (10 vs. 96months; 19 vs. 121months, p<0.0001). Post-surgical complications were observed in 36 (51.4%), the majority of which were Grade I/II infections. There was one peri-operative death. Review of the literature showed that chemotherapy, radiotherapy or combination treatments are alternatives to surgery. Evidence relating to all of these consisted mostly of small retrospective series, which varied considerably in terms of patient characteristics and treatment schedules. Significant patient and treatment heterogeneity prevented meta-analysis with significant biases in these studies. It was unclear if survival or morbidity was better in any one group with a lack of data reporting complications, quality of life, and long term follow-up. However, results for chemoradiation are encouraging enough to warrant further investigation. CONCLUSIONS: There remains inadequate evidence to identify an optimal treatment for LAVC. However, there is sufficient evidence to support a trial of anovulvectomy versus chemoradiation. Discussions and consensus would be needed to determine trial criteria including the primary outcome measure. Neoadjuvant chemotherapy or radiotherapy alone may be best reserved for the palliative setting or metastatic disease.

High-resolution imaging for the detection and characterisation of circulating tumour cells from patients with oesophageal, hepatocellular, thyroid and ovarian cancers.

Interest has increased in the potential role of circulating tumour cells in cancer management. Most cell-based studies have been designed to determine the number of circulating tumour cells in a given volume of blood. Ability to understand the biology of the cancer cells would increase the clinical potential. The purpose of this study was to develop and validate a novel, widely applicable method for detection and characterisation of circulating tumour cells. Cells were imaged with an ImageStream(X) imaging flow cytometer which allows detection of expression of multiple biomarkers on each cell and produces high-resolution images. Depletion of haematopoietic cells was by red cell lysis, leukocyte common antigen CD45 depletion and differential centrifugation. Expression of epithelial cell adhesion molecule, cytokeratins, tumour-type-specific biomarkers and CD45 was detected by immunofluorescence. Nuclei were identified with DAPI or DRAQ5 and brightfield images of cells were collected. The method is notable for the dearth of cell damage, recoveries greater than 50%, speed and absence of reliance on the expression of a single biomarker by the tumour cells. The high-quality images obtained ensure confidence in the specificity of the method. Validation of the methodology on samples from patients with oesophageal, hepatocellular, thyroid and ovarian cancers confirms its utility and specificity. Importantly, this adaptable method is applicable to all tumour types including those of nonepithelial origin. The ability to measure simultaneously the expression of multiple biomarkers will facilitate analysis of the cancer cell biology of individual circulating tumour cells.

Phosphatase and Tensin Homolog Is a Potential Target for Ovarian Cancer Sensitization to Cytotoxic Agents.

OBJECTIVES: The phosphatase and tensin homolog (PTEN) tumor suppressor protein has been found to be inactivated or mutated in various human malignancies and to play a role in cisplatin and poly(ADP-ribose) polymerase inhibitor sensitivity. In this study, we assessed the association of PTEN loss with homologous recombination (HR) deficiency and increased chemosensitivity. MATERIALS AND METHODS: The PTEN knockdown models were created using MISSION shRNA lentiviral transduction particles in cell lines derived from normal ovarian surface epithelium and a mixed endometrioid/clear-cell carcinoma. Sensitivity to common therapeutics was assessed using sulforhodamine B assay. Twenty-eight unselected primary epithelial ovarian cancer cultures derived from ascitic fluid collected at the time of surgery and matched genomic DNA were assessed for PTEN mutations using polymerase chain reaction amplification and Sanger sequencing and for mRNA expression using quantitative reverse transcription-polymerase chain reaction; HR was determined using γH2AX/RAD51 assay. The Cancer Genome Atlas data were analyzed using cBioPortal. RESULTS: In the carcinoma cell line, the PTEN knockdown enhanced sensitivity to cisplatin, rucaparib, doxorubicin, camptothecin, paclitaxel, and irradiation. In the primary ovarian cancer cultures, 2 point mutations were found (1105T>TG, 25L>L in 6 cultures and 1508G>GA, 159R>R in 4 cultures). The PTEN mRNA expression varied over 40-fold between the cultures, but did not correlate with HR status or in vitro sensitivity to cisplatin or rucaparib. The Cancer Genome Atlas data showed a rate of 8% alteration in PTEN and a trend toward improved survival in PTEN-mutated cases. CONCLUSIONS: These data indicate that although PTEN mutations in ovarian cancer are rare, PTEN inhibition results in therapeutic sensitization. Therefore, PTEN may be an important therapeutic target, in at least some cancers.