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Background Recently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC. Methods Two prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively). Six thousand four hundred and thirty-four (FOXJ1) and 5470 (GMNN) formalin-fixed, paraffin-embedded ovarian neoplasms (4634 and 4185 HGSC, respectively) represented on tissue microarrays from the Ovarian Tumor Tissue Analysis consortium underwent immunohistochemical staining and scoring, then univariate and multivariate survival analysis. Results Consistent with mRNA, FOXJ1 protein expression exhibited a linear, increasing association with improved overall survival in HGSC patients. Women with >50% expression had the most favourable outcomes (HR = 0.78, 95% CI 0.67–0.91, p 35% GMNN expression showed a trend for better outcomes, though this was not significant. Conclusion We provide foundational evidence for the prognostic value of FOXJ1 in HGSC, validating the prior mRNA-based prognostic association by immunohistochemistry.

Purpose: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. Experimental Design: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). Results: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). Conclusions: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.

Same-day discharge (SDD) in patients with endometrial cancer undergoing minimally invasive surgery (MIS) is safe and feasible, with multiple patient and healthcare system benefits. Despite this, our local rate of SDD was only 29.4%. Several studies have suggested methods to improve rates of SDD but few have evaluated the application of such methods. The objectives of our quality improvement (QI) initiative were 2-fold: (1) to increase the rate of SDD in eligible patients with endometrial cancer undergoing MIS to 70% and (2) to evaluate the implementation of methods to improve rates of SDD.At our center, QI diagnostics were conducted, and root causes were identified. Four interventions were introduced: (1) setting SDD as the default discharge plan, (2) ensuring that a physician order for discharge was on the chart, (3) removing the Foley catheter in the operating room, and (4) introducing pre- and postoperative patient education documents. A time-series design was used; rate of SDD was tracked using baseline data and continuous post-intervention monitoring. Process measures (for each intervention) and balancing measures were defined and tracked.At the conclusion of our QI initiative, the average rate of SDD was 78.3%-exceeding our aim of 70%. This was achieved without compromising patient satisfaction (98.2%) or significantly impacting rates of readmission or presentations to the emergency department.Our initiative demonstrated the application of simple interventions that resulted in a substantial increase in our rate of SDD in the population of interest, without causing negative impacts on the defined balancing measures. These interventions were nonspecific to gynecologic oncology and could easily be applied across other surgical disciplines.

Background: Women with Inflammatory Bowel Diseases (IBD) have fewer children and stay childless more often. The decision-making process around family planning choices remains incompletely understood. Methods: We examined family status in women who at recruitment to the UK IBD Bioresource had not had children yet via an electronic survey. The primary outcome was the proportion of women with voluntary childlessness. Secondary outcomes were factors associated with family planning status. Results: Of 326 responders, 10.7% had either given birth, were currently pregnant or were currently trying to conceive; 12.6% were planning to conceive within 12 months; 54.4% were contemplating conception in the distant future (vague plans); and 22.3% were voluntarily childless. Factors associated with family planning status fell into three areas: general background (age, household income, perceived support to raise a child), relationship status (sexual orientation, being single, not cohabiting, perception of being ‘in the right relationship to raise a child’, perception of a good sex life) and the expression of having a child as a goal in life. On binary logistics regression analysis with voluntary childlessness versus vague family plans as the outcomes of choice, having a household income of

Supplementary Methods

Supplementary Figures S1-S13

Purpose:Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features.Experimental Design:Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55).Results:Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%).Conclusions:An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.

Supplementary Tables S1-S11

Background: Comorbidities can affect survival of ovarian cancer patients by influencing treatment efficacy. However, little evidence exists on the association between individual concurrent comorbidities and prognosis in ovarian cancer patients.Methods: Among patients diagnosed with invasive ovarian carcinoma who participated in 23 studies included in the Ovarian Cancer Association Consortium, we explored associations between histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, and neurological diseases and overall and progression-free survival. Using Cox proportional hazards regression models adjusted for age at diagnosis, stage of disease, histology, and study site, we estimated pooled HRs and 95% confidence intervals to assess associations between each comorbidity and ovarian cancer outcomes.Results: None of the comorbidities were associated with ovarian cancer outcome in the overall sample nor in strata defined by histologic subtype, weight status, age at diagnosis, or stage of disease (local/regional vs. advanced).Conclusions: Histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, or neurologic diseases were not associated with ovarian cancer overall or progression-free survival.Impact: These previously diagnosed chronic diseases do not appear to affect ovarian cancer prognosis. Cancer Epidemiol Biomarkers Prev; 26(9); 1470–3. ©2017 AACR.

Description of the studies included in the pooled analysis and methods of data collection

Summary Background There is a paucity of evidence to support safe and effective management of patients with acute severe ulcerative colitis during the COVID-19 pandemic. We sought to identify alterations to established conventional evidence-based management of acute severe ulcerative colitis during the early COVID-19 pandemic, the effect on outcomes, and any associations with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes. Methods The PROTECT-ASUC study was a multicentre, observational, case-control study in 60 acute secondary care hospitals throughout the UK. We included adults (≥18 years) with either ulcerative colitis or inflammatory bowel disease unclassified, who presented with acute severe ulcerative colitis and fulfilled the Truelove and Witts criteria. Cases and controls were identified as either admitted or managed in emergency ambulatory care settings between March 1, 2020, and June 30, 2020 (COVID-19 pandemic period cohort), or between Jan 1, 2019, and June 30, 2019 (historical control cohort), respectively. The primary outcome was the proportion of patients with acute severe ulcerative colitis receiving rescue therapy (including primary induction) or colectomy. The study is registered with ClinicalTrials.gov , NCT04411784 . Findings We included 782 patients (398 in the pandemic period cohort and 384 in the historical control cohort) who met the Truelove and Witts criteria for acute severe ulcerative colitis. The proportion of patients receiving rescue therapy (including primary induction) or surgery was higher during the pandemic period than in the historical period (217 [55%] of 393 patients vs 159 [42%] of 380 patients; p=0·00024) and the time to rescue therapy was shorter in the pandemic cohort than in the historical cohort (p=0·0026). This difference was driven by a greater use of rescue and primary induction therapies with biologicals, ciclosporin, or tofacitinib in the COVID-19 pandemic period cohort than in the historical control period cohort (177 [46%] of 387 patients in the COVID-19 cohort vs 134 [36%] of 373 patients in the historical cohort; p=0·0064). During the pandemic, more patients received ambulatory (outpatient) intravenous steroids (51 [13%] of 385 patients vs 19 [5%] of 360 patients; p=0·00023). Fewer patients received thiopurines (29 [7%] of 398 patients vs 46 [12%] of 384; p=0·029) and 5-aminosalicylic acids (67 [17%] of 398 patients vs 98 [26%] of 384; p=0·0037) during the pandemic than in the historical control period. Colectomy rates were similar between the pandemic and historical control groups (64 [16%] of 389 vs 50 [13%] of 375; p=0·26); however, laparoscopic surgery was less frequently performed during the pandemic period (34 [53%] of 64] vs 38 [76%] of 50; p=0·018). Five (2%) of 253 patients tested positive for SARS-CoV-2 during hospital treatment. Two (2%) of 103 patients re-tested for SARS-CoV-2 during the 3-month follow-up were positive 5 days and 12 days, respectively, after discharge from index admission. Both recovered without serious outcomes. Interpretation The COVID-19 pandemic altered practice patterns of gastroenterologists and colorectal surgeons in the management of acute severe ulcerative colitis but was associated with similar outcomes to a historical cohort. Despite continued use of high-dose corticosteroids and biologicals, the incidence of COVID-19 within 3 months was low and not associated with adverse COVID-19 outcomes. Funding None.

The COVID-19 pandemic disrupted healthcare services across the world with only essential care being continued.1 2 For paediatric and adult patients with inflammatory bowel disease (IBD), this resulted in significant changes to accessing health services. In some services, IBD advice lines were stopped, specialist nurses and medical staff were redeployed to support acute admissions, outpatient clinics were deferred, and home care services were under threat.3 4 In addition, there was a reluctance from patients to come to hospital or contact their services due to concerns over their personal safety.5 6 The Crohn's and Colitis United Kingdom (CCUK) ‘life in lockdown’ patient survey reported that patients felt their IBD teams kept them well informed of coronavirus and their condition. Importantly, one in five patients reported that they also received inaccurate information on other aspects such as shielding.7 The pandemic has also highlighted the disparities in accessing healthcare8 and addressing these alongside organisational transformation will support personalised care, which is one of the main recommendations of the Inflammatory Bowel Disease United Kingdom (IBD UK) standards.9 Healthcare services have restarted routine clinical practices responding swiftly to regional and national lockdowns in the second wave.10 Additionally, local data have allowed clinical teams to refine service delivery supporting those most vulnerable to poorer outcomes if they develop COVID-19.11 12 The British Society of Gastroenterology (BSG) has commissioned independent reviews on the redesign of outpatient services focusing on telemedicine and restarting endoscopy safely.13–20 The COVID-19 pandemic effect on clinical research and trial activity are being addressed separately by the BSG IBD research committee.1 21 We are currently in our second wave of the pandemic and a third national lockdown with increasing pressure to maintain specialist services as well as directly supporting care for patients with COVID-19. …

IntroductionDuring COVID-19, the management of outpatient inflammatory bowel disease (IBD) changed from face-to-face (F2F) to telephone and video consultations across the UK. We surveyed patients with IBD and IBD healthcare professionals (HCPs) to evaluate the impact of this abrupt transition on patient and HCP satisfaction outcomes, including the barriers and enablers of this service.MethodsPatient satisfaction surveys were sent to patients who had a telephone consultation from May to July 2020. A second survey was sent to IBD HCPs across the UK. Questions from both surveys consisted of a mixture of multiple-choice options, ranking answers as well as short-answer questions.Results210 patients and 114 HCPs completed the survey. During COVID-19, there was a significantly greater use of telephone, video or a mixture of consultation. F2F consultations were consistently preferred by patients, with 50% of patients indicating they did not want the option of for video consultations. Patients were more likely to prefer a telephone consultation if they were stable and needed routine review. Significantly fewer HCPs (5.3%) intend to use F2F consultations alone, preferring the use of telephone (20.2%) or combinations of telephone/F2F (22.8%), telephone/video (4.4%) or combination of all three consultation types (34.2%). 63% indicated they intend to incorporate video consultations in the future.ConclusionTelephone and video consultations need to be balanced proportionately with F2F clinics to achieve both patient and HCP satisfaction. Further research needs to be done to explore the use of video medicine in patients with IBD.

Introduction: There are numerous confounding variables in the pre-analytical steps in the analysis of gut microbial composition that affect data consistency and reproducibility. This study compared two DNA extraction methods from the same faecal samples to analyse differences in microbial composition. Methods: DNA was extracted from 20 faecal samples using either (A) chemical/enzymatic heat lysis (lysis buffer, proteinase K, 95 °C + 70 °C) or (B) mechanical and chemical/enzymatic heat lysis (bead-beating, lysis buffer, proteinase K, 65 °C). Gut microbiota was mapped through the 16S rRNA gene (V3–V9) using a set of pre-selected DNA probes targeting >300 bacteria on different taxonomic levels. Apart from the pre-analytical DNA extraction technique, all other parameters including microbial analysis remained the same. Bacterial abundance and deviations in the microbiome were compared between the two methods. Results: Significant variation in bacterial abundance was seen between the different DNA extraction techniques, with a higher yield of species noted in the combined mechanical and heat lysis technique (B). The five predominant bacteria seen in both (A) and (B) were Bacteroidota spp. and Prevotella spp. (p = NS), followed by Bacillota (p = 0.005), Lachhnospiraceae (p = 0.0001), Veillonella spp. (p < 0.0001) and Clostridioides (p < 0.0001). Conclusion: As microbial testing becomes more easily and commercially accessible, a unified international consensus for optimal sampling and DNA isolation procedures must be implemented for robustness and reproducibility of the results.

Funder: Funding details are provided in the Supplementary Material, Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally-efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, ���select and shrink for summary statistics��� (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestry; 7,669 women of East Asian ancestry; 1,072 women of African ancestry, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestry. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38(95%CI:1.28���1.48,AUC:0.588) per unit standard deviation, in women of European ancestry; 1.14(95%CI:1.08���1.19,AUC:0.538) in women of East Asian ancestry; 1.38(95%CI:1.21-1.58,AUC:0.593) in women of African ancestry; hazard ratios of 1.37(95%CI:1.30���1.44,AUC:0.592) in BRCA1 pathogenic variant carriers and 1.51(95%CI:1.36-1.67,AUC:0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.

Purpose: Gene expression–based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features. Experimental Design: Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting. Results: Gene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor-infiltrating lymphocytes, and outcome. The locked-down clinical grade PrOTYPE test includes a model with 55 genes that predicted gene expression subtype with >95% accuracy that was maintained in all analytic and biological validations. Conclusions: We validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications. See related commentary by McMullen et al., p. 5271

ObjectiveThiopurines are widely used as maintenance therapy in inflammatory bowel disease (IBD) but the evidence base for their use is sparse and their role increasingly questioned. Using the largest series reported to date, we assessed the long-term effectiveness of thiopurines in ulcerative colitis (UC) and Crohn’s disease (CD), including their impact on need for surgery.DesignOutcomes were assessed in 11 928 patients (4968 UC, 6960 CD) in the UK IBD BioResource initiated on thiopurine monotherapy with the intention of maintaining medically induced remission. Effectiveness was assessed retrospectively using patient-level data and a definition that required avoidance of escalation to biological therapy or surgery while on thiopurines. Analyses included overall effectiveness, time-to-event analysis for treatment escalation and comparison of surgery rates in patients tolerant or intolerant of thiopurines.ResultsUsing 68 132 patient-years of exposure, thiopurine monotherapy appeared effective for the duration of treatment in 2617/4968 (52.7%) patients with UC compared with 2378/6960 (34.2%) patients with CD (pConclusionThiopurine monotherapy is an effective long-term treatment for UC but significantly less effective in CD.

Objective This study sought to evaluate the use of the Edmonton Obesity Staging System (EOSS) in predicting cesarean delivery among term, nulliparous, singleton pregnancies in women with overweight or obesity who are undergoing an induction of labour. Methods A prospective cohort study was performed in Edmonton, Alberta. Women undergoing an induction of labour at term were recruited to either a sample cohort, including women with a body mass index of ≥25 kg/m2 at first antenatal visit, or a control cohort with a body mass index of 18.5 to 24.9 kg/m2. Participating women provided a self-reported health history and consented to review of their medical records allowing allocation into EOSS categories. The primary outcome was the rate of cesarean delivery based on EOSS category. Secondary outcomes consisted of a summary score of adverse maternal, delivery, and neonatal events (Canadian Task Force Classification II-2). Results Overall, 345 women were recruited, with a participation rate of 93.7%. The sample cohort consisted of 276 women with overweight or obesity, whereas the control cohort included 69 normal-weight women. The overall rate of cesarean delivery was 30.4% for the control cohort and 35.8%, 29.9%, 43.2%, and 90.5% for women assigned an EOSS category 0, 1, 2, and 3, respectively (P Conclusion The EOSS may help predict the chance of cesarean delivery in a high-risk group of nulliparous women with overweight or obesity who are undergoing an induction of labour at term.

IntroductionCompared with other medical specialties, there are lower numbers of female trainees and lower rates of flexible working in gastroenterology. This study aims to examine the experience of male and female trainees to understand specialty demographics and the experience of training.MethodsGastroenterology training data were obtained from the British Society of Gastroenterology (BSG) trainee surveys from 2014, 2018 and 2020, and from the Royal College of Physicians Medical Workforce unit between 2011 and 2019. Data on endoscopy measures from 2011 to 2021 were obtained from the Joint Advisory Group (JAG) on gastrointestinal endoscopy, including the JAG Endoscopy training system and the National Endoscopy Database. Data were segregated and compared by gender.ResultsThe percentage of female gastroenterology trainees remains at around 40%, largely unchanged over the previous decade. From the BSG trainee survey, 29.5% of women have flexible working patterns compared with 2.6% of men (pConclusionChanges must be addressed from a national and institutional level to address equitable access to national training programmes and equality of outcome for male and female trainees.

PEG has been associated with poor case selection and high mortality. We examined indications, 30-day mortality, and 7-day adverse events in a national cohort undergoing PEG tube insertion.Adult patients undergoing their first PEG tube insertion from 2007 to 2019 were identified in the Hospital Episode Statistics database. Indications and adverse events were identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes. Multivariable logistic regression modeling examined factors associated with mortality.Of 87,682 patients identified, 58% were men and median age was 69 years (interquartile range, 57-79). The number of patients with dementia or stroke as the indication for PEG fell from 2007 to 2019 (dementia, from 147 to 28 [P .001]; stroke, from 2851 to 1781 [P .001]). The median interval from stroke admission to PEG tube insertion increased from 21 (interquartile range, 12-36) to 28 (interquartile range, 13-45) days (P .001). Aspiration pneumonia within 7 days of PEG fell from 10.2% to 8.6% (P = .04). Thirty-day mortality fell from 13.2% to 5.3% (P .001), with associated factors of increasing age (≥82 years quintile odds ratio [OR], 4.44; 95% confidence interval [CI], 4.01-4.92), PEG tube insertion during emergency admission (OR, 2.10; 95% CI, 1.97-2.25), Charlson comorbidity score ≥5 (OR, 1.67; 95% CI, 1.53-1.82), and dementia (OR, 1.46; 95% CI, 1.26-1.71). Female sex (OR, .81; 95% CI, .77-.85), least-deprived quintile (OR, .88; 95% CI, .81-.95), and more recent years of PEG tube insertion (2019; OR, .44; 95% CI, .39-.51) were negatively associated with mortality.Thirty-day mortality after PEG tube insertion has fallen 60% over 13 years. Dementia or stroke as an indication for PEG fell, and the time interval from stroke to PEG tube insertion increased. These findings may be attributable to improved patient selection and timing for PEG tube insertion.

This is an accepted manuscript of an abstract presented at BSG Annual Meeting 2021, published by BMJ/British Society of Gastroenterology in Gut (in press). The accepted version of the publication may differ from the final published version.

To compare the immediate operating room (OR), inpatient, and overall costs between three surgical modalities among women with endometrial cancer (EC) and Class III obesity or higher.A multicentre prospective observational study examined outcomes of women, with early stage EC, treated surgically. Resource use was collected for OR costs including OR time, equipment, and inpatient costs. Median OR, inpatient, and overall costs across surgical modalities were analyzed using an Independent-Samples Kruskal-Wallis Test among patients with BMI ≥ 40.Out of 520 women, 103 had a BMI ≥ 40. Among women with BMI ≥ 40: median OR costs were $4197.02 for laparotomy, $5524.63 for non-robotic assisted laparoscopy, and $7225.16 for robotic-assisted laparoscopy (p 0.001) and median inpatient costs were $5584.28 for laparotomy, $3042.07 for non-robotic assisted laparoscopy, and $1794.51 for robotic-assisted laparoscopy (p 0.001). There were no statistically significant differences in the median overall costs: $10 291.50 for laparotomy, $8412.63 for non-robotic assisted laparoscopy, and $9002.48 for robotic-assisted laparoscopy (p = 0.185).There was no difference in overall costs between the three surgical modalities in patient with BMI ≥ 40. Given the similar costs, any form of minimally invasive surgery should be promoted in this population.

Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan–Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naïve HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81–0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naïve tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naïve HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36–0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.

Simple Summary Anemia is commonly associated with colorectal cancer and often requires intervention with therapeutic iron. However, iron is required for growth by the majority of colonic bacteria, leading to competition for free luminal iron. Hence, this leaves the potential for the route of iron administration to lead to differential gut bacterial populations. This study aimed to investigate the differences in on- and off-tumor bacterial populations following oral and intravenous therapy in anemic colorectal cancer patients. The following iron therapies were shown to be differential to bacterial diversity, microbial populations, and predictive metagenomics, inferring that oral iron-treated patients may have a potentially more procarcinogenic microbiota compared to intravenous iron-treated patients. Overall, this suggests that intravenous iron may be a more beneficial treatment for anemia in colorectal cancer, in order to limit microbial perturbations associated with oral iron. Abstract Iron deficiency anemia is a common complication of colorectal cancer and may require iron therapy. Oral iron can increase the iron available to gut bacteria and may alter the colonic microbiota. We performed an intervention study to compare oral and intravenous iron therapy on the colonic tumor-associated (on-tumor) and paired non-tumor-associated adjacent (off-tumor) microbiota. Anemic patients with colorectal adenocarcinoma received either oral ferrous sulphate (n = 16) or intravenous ferric carboxymaltose (n = 24). On- and off-tumor biopsies were obtained post-surgery and microbial profiling was performed using 16S ribosomal RNA analysis. Off-tumor α- and β-diversity were significantly different between iron treatment groups. No differences in on-tumor diversity were observed. Off-tumor microbiota of oral iron-treated patients showed higher abundances of the orders Clostridiales, Cytophagales, and Anaeroplasmatales compared to intravenous iron-treated patients. The on-tumor microbiota was enriched with the orders Lactobacillales and Alteromonadales in the oral and intravenous iron groups, respectively. The on- and off-tumor microbiota associated with intravenous iron-treated patients infers increased abundances of enzymes involved in iron sequestration and anti-inflammatory/oncogenic metabolite production, compared to oral iron-treated patients. Collectively, this suggests that intravenous iron may be a more appropriate therapy to limit adverse microbial outcomes compared to oral iron.

To retrospectively review the efficacy of short term supervised medical weight loss for women with obesity, body mass index (BMI ≥40 kg/m2 ) in gynaecologic oncology, and the associated perioperative and pathologic outcomes. A retrospective study of a dedicated preoperative weight loss clinic for gynaecologic oncology patients from March to December 2019. Statistical analysis was performed with McNemar's test for correlated proportions, Pearson's correlation tests for continuous variables, and paired t-tests to compare means. Generalized estimating equations (GEE) were used to determine the factors associated with weight loss over time. A P-value of

SARS-CoV-2 has caused a global health crisis and mass vaccination programmes provide the best opportunity for controlling transmission and protecting populations. Despite the impressive clinical trial results of the BNT162b2 (Pfizer/BioNTech), ChAdOx1 nCoV-19 (Oxford/AstraZeneca), and mRNA-1273 (Moderna) vaccines, important unanswered questions remain, especially in patients with pre-existing conditions. In this position statement endorsed by the British Society of Gastroenterology Inflammatory Bowel Disease (IBD) section and IBD Clinical Research Group, we consider SARS-CoV-2 vaccination strategy in patients with IBD. The risks of SARS-CoV-2 vaccination are anticipated to be very low, and we strongly support SARS-CoV-2 vaccination in patients with IBD. Based on data from previous studies with other vaccines, there are conceptual concerns that protective immune responses to SARS-CoV-2 vaccination may be diminished in some patients with IBD, such as those taking anti-TNF drugs. However, the benefits of vaccination, even in patients treated with anti-TNF drugs, are likely to outweigh these theoretical concerns. Key areas for further research are discussed, including vaccine hesitancy and its effect in the IBD community, the effect of immunosuppression on vaccine efficacy, and the search for predictive biomarkers of vaccine success.

Background Iron deficiency anaemia is a common complication of colorectal cancer and may require iron therapy. Oral iron can increase iron available to gut bacteria and may alter the colonic microbiota. We performed an intervention study to compare oral and intravenous iron therapy on the colonic tumour-associated (on-tumour) and paired non-tumour-associated adjacent (off-tumour) microbiota. Anaemic patients with colorectal adenocarcinoma received either oral ferrous sulphate (n=16) or intravenous ferric carboxymaltose (n=24). On- and off-tumour biopsies were obtained post-surgery and microbial profiling was performed using 16S ribosomal RNA analysis.Results Off-tumour α- and β-diversity were significantly different between iron treatment groups. No differences in on-tumour diversity were observed. Off-tumour microbiota of oral iron-treated patients shows higher abundances of the orders Clostridiales, Cytophagales and Anaeroplasmatales compared to intravenous iron-treated patients. The on-tumour microbiota was enriched with the orders Lactobacillales and Alteromonadales in the oral and intravenous iron groups, respectively. The on- and off-tumour microbiota associated with intravenous iron-treated patients infers increased abundances of enzymes involved in iron sequestration and anti-inflammatory/oncogenic metabolite production, compared to oral iron-treated patients. Paired on- and off-tumour microbiota show large taxonomic differences in intravenous iron-treated patients and limited differences in oral iron-treated patients.Conclusion Oral iron shows a large shift in the off-tumour microbiota, but a more limited change in on-tumour microbiota. The on- and off-tumour microbiota in intravenous iron-treated patients infers a microbiota associated with anti-inflammatory and tumour protective pathways. Suggesting intravenous iron may be a more appropriate therapy to limit adverse microbial outcomes, compared to oral iron.Trial registration: NCT01701310. Registered 21 March 2012, https://clinicaltrials.gov/ct2/show/NCT01701310

Background Inflammatory bowel disease (IBD) is a chronic illness affecting patients in their childbearing years. The physical effects of IBD on fertility and pregnancy in IBD in remission (e.g. disease is well controlled during conception and throughout pregnancy) are similar to the normal population. However, many women with IBD have high pregnancy-related anxieties and are more likely not to have children compared to women without IBD. The reasons cited for not having children include high levels of pregnancy-related anxieties have been insufficiently explored. The study aimed to explore the lived experience of family planning of women with inflammatory bowel disease (IBD) and their partners with or without IBD, during the reproductive stages of pre-conception, pregnancy and the postnatal period. Methods Descriptive phenomenology was used to conduct face-to-face in-depth individual interviews. Purposive sampling was used to select participants with a maximum variation of different demographic and clinical factors, e.g. age, sex, UC/CD diagnosis, disease duration, surgery, geographic location. The NVivo 12 software programme was used to manage the data and Colaizzi’s framework was utilised in thematic data analysis. Results 24 participants (21 women 11CD/10UC and 3 partners) were recruited from out-patient clinics (22 participants) or through the Crohn’s and Colitis UK website (2 participants). Women, average age 31 years of age (range 27–38), were at different family planning stages: pre-conception 6 women (3 actively planning family and 3 voluntarily childless); pregnant 8 women and 2 partners; and postpartum 7 women and one partner. Three women’s partners, age 32–39, were recruited allowing for additional perspective of the experience being captured. In total 19 hours of interviews data were collected. Six themes were identified: i) being diagnosed and controlling IBD symptoms; ii) relationship and family planning; iii) sources of information; iv) worries and concerns about pregnancy; v) post pregnancy care and problems; vi) ways of improving care. Women in pre-pregnancy stage and pregnant expressed a need for more information around these themes: (i) their medication and the impact of IBD on the baby; (ii) the genetic risk of passing the disease on. While pregnant and during post-partum stage, women identified a greater need for practical advice and support in relation to breastfeeding and looking after the baby. Conclusion Information specific to family planning stages need to be provided, to help women and their partners make the informed decision about family planning. Those who decided not to go down the family route, also expressed a need for counselling and support.

Introduction To evaluate the clinical and biochemical outcomes of patients with inflammatory bowel disease to Vedolizumab- at a District General Hospital Methodology Retrospective cohort study assessing 55 patients administered Vedolizumab between 2015 and 2019. Demographics and clinical information were recorded. Response was determined using Harvey Bradshaw (HB) and partial Mayo score (pMS). Baseline indices and serum CRP were recorded at (i) prior to commencement, (ii) 6 months, and (iii) 12 months. A clinical response was determined by a decrease in pMS and HB of at least 3 points for UC and CD respectively or to a score below 5. Results A total of 55 patients (33 CD, 22 UC) were found on our electronic records. A total of 44(18 UC, 26 CD) were included with 11 patients excluded as they had started within 6 months of study commencement. Mean age for UC was 45.2 years and CD was 42.8 years, 15/18(83.3%) UC patients and 20/26 (76.9%) CD patients had prior anti TNF exposure. 56% (5/9) of all those TNF naive were found to have a response at 6 months. UC group Mean CRP reduction at 6 and 12 months was -7.1 and -6.3 respectively. Mean pMS prior to treatment 5.8 and at 6 months was 4.8. At 6 months, 6% (n=1/18) were responders, 61% (11/18) were partial responders and 33% (n=6/18) were non responders. 67% (n=12/18) completed 12 months treatment when 8%(n=1/12) were responders, 58% (n=7/12) partial responders and 33% (n=4/12) were non responders. CD group Mean CRP reduction at 6 and 12 months were -7.7 and -7.2 respectively. Mean HB prior to treatment 7.7 and at 6 months was 5.7. At 6 months, 19%( n=5/26) were in clinical remission, 15% (n=4/26) were responders, 46% (n=12/26) were partial responders and 19% (n=5/26) non responders. 65% (n=17/26) completed 12 months treatment, of those 23.5% (n=4/17) were in clinical remission, 17.6%( n=3/17) were responders, 41% (n=7/17) were partial responders and 17.6% (n= 3/17) were non responders. Reasons for stopping treatment in all patients: treatment was stopped prior to completion of 12 months in 15/44(34%) patients. This included need for surgery 4.5% (2/44), abnormal liver function tests 9%(n=4/44), intolerance 18% (8/44), and pregnancy 2.2% (1/44). Conclusion Our results reflect similar safety and efficacy of Vedolizumab to published data. Vedolizumab was generally well tolerated with no serious adverse effects.

Determining energy requirements is vital for optimizing nutrition interventions in pro-catabolic conditions such as cancer. Gynecological cancer encompasses the most common malignancies in women, yet there is a paucity of research on its metabolic implications. The aim of this review was to explore the literature related to energy metabolism in gynecological cancers. We were particularly interested in exploring the prevalence of energy metabolism abnormalities, methodological approaches used to assess energy metabolism, and clinical implications of inaccurately estimating energy needs. A search strategy was conducted from inception to 27 July 2021. Studies investigating energy metabolism using accurate techniques in adults with any stage of gynecological cancer and the type of treatment were considered. Of the 874 articles screened for eligibility, five studies were included. The definition of energy metabolism abnormalities varied among studies. Considering this limitation, four of the five studies reported hypermetabolism. One of these studies found that hypermetabolism was more prevalent in ovarian compared to cervical cancer. Of the included studies, one reported normometabolism at the group level; individual-level values were not reported. One of the studies reported hypermetabolism pre- and post-treatment, but normometabolism when re-assessed two years post-treatment. No studies explored clinical implications of inaccurately estimating energy needs. Overall, commonly used equations may not accurately predict energy expenditure in gynecological cancers, which can profoundly impact nutritional assessment and intervention.

Background Enteral feeding tubes are associated with their most serious complications in the days and weeks after insertion, but there is limited published data in the literature on late complications and the implications for the healthcare service. Methods Retrospective observational study of attendances to a UK hospital emergency department with enteral tube complications as the primary reason for attendance. Results Over 24 months 139 attendances were recorded. Dislodged tubes and blocked tubes accounted for the majority of complications and subsequent admissions, with a mixture of enteral tube types being associated with both. Thirty-five percent were admitted and the average healthcare cost per attendance was $1071. Conclusions Enteral tube complications can place a hidden burden on the patient, on ED and on healthcare costs. More work on education and supporting carers to resolve problems themselves could reduce the burden on busy emergency departments. This article is protected by copyright. All rights reserved.

Background PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study. Methods Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran–Mantel–Haenszel tests. Results Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65–0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value p value = 0.019) and associated with higher CD8 counts (p value = 0.0016). Conclusions PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.

AIM AND OBJECTIVES To identify the practice variation of the individual practitioners in medications' formulation modification for patients using enteral feeding tubing and to support health practitioners involved in this process. BACKGROUND Blockage of enteral tubes is a common problem that can sometimes be resolved but may require replacement of the tube. Medications are a common culprit. DESIGN A survey of 73 registered nurses' practices around medication administration via enteral feeding tubes. METHODS A questionnaire study was undertaken within a district general hospital across a broad variety of wards to explore nurses' experiences of medication administration via enteral tubes. The study is reported in accordance with the squire 2.0 guidelines from the EQUATOR network. RESULTS Seventy-three nurses responded. Twenty-six per cent reported never checking about drug modification for administration via a tube, 12% check every time and 61% when unsure about a new drug. The volume of fluid flushes administered after medication ranged from 7.5-150 ml. Seventy-one per cent of participants reported stopping feed when medications are required, varying from 1-60 min. Sixty per cent had experienced a blocked tube and 52% the tube being removed for these reasons. The clinical nurse specialist was the commonest first point of call to help. Staff named 15 medications as the most problematic to administer, lactulose and omeprazole were the top two. CONCLUSIONS Practice varies significantly amongst nurses around medication administration. Theoretically, this may contribute to blocked tubes and excessive fluid administration to some patients. Barriers to medication administration were thematically grouped into: time, difficulty modifying medication, medication interactions and knowledge. Areas identified to support staff include training, devices to crush medications, medication suitability, multidisciplinary approach to streamline care and quick reference guides. RELEVANCE TO CLINICAL PRACTICE Health professionals may use these results to reduce and ultimately avoid problems with administering medications through feeding tubes. Organisations may use these results to develop their local practice pathways for prescribing, dispensing and training around administration of medications through enteral tubes. In a community setting, this paper may improve the awareness of patients, caregivers and prescribers of the possible implications of tubing blockages.