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Objective: To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival. Patients and Methods: We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong). Results: Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P

Objectives: Lymphadenectomy as part of surgical staging for endometrial cancer can define risk of recurrence and guide clinical decision-making for adjuvant therapy. While sentinel lymph node (SLN) mapping significantly reduces surgical complications and conserves an element of staging, its clinical significance remains controversial. The purpose of this study was to evaluate the incidence of SLN metastases and to identify risk factors and outcomes associated with positive SLNs. Methods: An international population-based retrospective review in three tertiary care academic centers was conducted on patients with endometrial cancer undergoing SLN biopsy as part of surgical staging for apparent early stage endometrial cancer. Multivariate logistic regression was performed to assess predictors of SLN positivity and to estimate the effect of SLN metastases on overall survival (OS) and progression-free survival (PFS). Results: One thousand and twelve patients were included with an average age of 60 years (24-90). The majority of women had Stage IA (68.9%) and low-grade histology (76.9%). Indocyanine green was used to identify SLNs in 535 (52.9%) women with an overall uptake at the whole-patient level of 94.0%. The overall incidence of SLN metastases was 5.7% (n=58). Cancer Antigen 125 > 35U/mL (OR=3.8 95% CI: 1.4-10.5; p=0.013) and presence of lymphovascular space invasion (OR=15.8, 95% CI: 5.6-44.7; p Conclusions: This is the largest international multicentered study evaluating SLN identification in endometrial cancer. Cancer Antigen 125 was identified as a preoperative independent risk factor associated with SLN positivity and can be used to optimize patient selection and surgical planning. Our data support the current literature suggesting that SLN biopsy for endometrial cancer should become standard of care. The procedure is associated with minimal morbidity and mortality, and has excellent performance.

Synchronous endometrial and ovarian tumors (SEOs) are diagnosed in 10% of ovarian cancer patients. We examined predictors of SEOs, evaluated associations of SEOs with survival and characterized ovarian tumor profiles using immunohistochemistry. We included patients with endometrioid (n = 180) and clear cell (n = 165) ovarian carcinoma identified from the Alberta Cancer Registry between 1979 and 2010 for whom we abstracted medical records and constructed tumor tissue microarrays (TMAs). A concurrent diagnosis of endometrial cancer was obtained from the medical chart. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs. Protein expression in ovarian tumors of patients with and without SEOs was evaluated using Fisher’s exact test. Comparing 52 patients with SEO tumors to 293 patients with endometrioid or clear cell ovarian carcinomas, endometriosis at the ovary (OR = 0.45, 95% CI = 0.23–0.87, p = 0.02) was the strongest predictor of decreased risk in multivariable models. Premenopausal status (OR = 2.17, 95% CI = 0.92–5.13, p = 0.08) and lower pre-treatment CA125 levels (OR = 0.17, 95% CI = 0.02–1.32, p = 0.09) showed weaker associations. There were no significant differences in survival between patients with or without SEO tumors. More patients with SEO tumors compared to endometrioid ovarian carcinoma were deficient in MLH1, PMS2 and PTEN (p ≤ 0.03). Endometriosis may not be the mechanism by which SEO cancers arise. Altered tumor oncoprotein expression between women with and without SEOs indicates important biological differences although this did not translate into prognostic differences.

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 with 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 and geographic location. The NVivo 12 software programme was used to manage the data and Colaizzi’s framework was utilised in thematic data analysis. Results Twenty-four participants (21 women 11CD/10UC and three partners) were recruited from out-patient clinics (22 participants) or through the Crohn’s and Colitis UK website (two participants). Women, average age 31 years old (range 27–38), were at different family planning stages: pre-conception six women (three actively planning family and three voluntarily childless); pregnant eight women and two partners; and postpartum seven 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 h of interviews data were collected. Six themes were identified: (1) being diagnosed and controlling IBD symptoms, (2) relationship and family planning, (3) sources of information, (4) worries and concerns about pregnancy, (5) post pregnancy care and problems and (6) ways of improving care. Women in pre-pregnancy stage and pregnant expressed a need for more information around these themes: (1) their medication and the impact of IBD on the baby, (2) 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.

Background The risk for epithelial ovarian cancer associated with the consumption of caffeinated beverages (tea, coffee, and soft drinks) and green tea is inconclusive. However, few studies have investigated the type of caffeinated beverage or the type of tea. Objective We assessed consumption of tea (black/caffeinated tea and green tea separately), coffee, and caffeinated soft drinks, as well as level of consumption, and the risk for epithelial ovarian cancer and its histotypes. Study design This study was conducted within a population-based case-control study in Alberta and British Columbia, Canada from 2001 to 2012. After restricting to cases of epithelial invasive cancers and controls aged 40–79 years who completed an interview that included coffee, soft drink, and tea consumption (ascertained starting in 2005 in British Columbia and 2008 in Alberta), there were a total of 524 cases and 1587 controls. Those that did not meet the threshold for beverage consumption (at least once per month for 6 months or more) were classified as non-drinkers. Adult lifetime cumulative consumption (cup-years = cups/day * years) was calculated. Unconditional logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) to describe the association between the relevant drink consumption and risk. Results No excess risk was seen for coffee or caffeinated soft drinks. Similarly, any tea consumption was not associated with risk, but when stratified by the type of tea, there was an increase in risk in black tea only drinkers (aOR = 1.56; 95% CI:1.07–2.28 for >40 cup-years), but no excess risk for the exclusive green tea drinkers. Similar findings were observed for post-menopausal women. The association for black tea only consumption was mainly seen in the endometrioid histotype (aOR = 3.19; 95% CI: 1.32–7.69). Conclusion Black tea consumption may be associated with an increased risk epithelial ovarian carcinoma. The excess risk is seen only in the endometrioid histotype but not in serous or clear cell. Further studies are required to confirm these findings and identify the constituents in black tea that may increase the risk.

Primary ovarian mucinous tumors can be difficult to distinguish from metastatic gastrointestinal neoplasms by histology alone. The expected immunoprofile of a suspected metastatic lower gastrointestinal tumor is CK7-/CK20+/CDX2+/PAX8-. This study assesses the addition of a novel marker SATB2, to improve the diagnostic algorithm. A test cohort included 155 ovarian mucinous tumors (105 carcinomas and 50 borderline tumors) and 230 primary lower gastrointestinal neoplasms (123 colorectal adenocarcinomas and 107 appendiceal neoplasms). All cases were assessed for SATB2, PAX8 CK7, CK20, and CDX2 expression on tissue microarrays. Expression was scored in a 3-tier system as absent, focal (1-50% of tumor cells) and diffuse ( >50% of tumor cells) and then categorized into either absent/present or nondiffuse/diffuse. SATB2 and PAX8 expression was further evaluated in ovarian tumors from an international cohort of 2876 patients (expansion cohort, including 159 mucinous carcinomas and 46 borderline mucinous tumors). The highest accuracy of an individual marker in distinguishing lower gastrointestinal from ovarian mucinous tumors was CK7 (91.7%, nondiffuse/diffuse cut-off) followed by SATB2 (88.8%, present/absent cut-off). The most effective combination was CK7 and SATB2 with accuracy of 95.3% using the 3-tier interpretation, absent/focal/diffuse. This combination outperformed the standard clinical set of CK7, CK20 and CDX2 (87.5%). Re-evaluation of outlier cases confirmed ovarian origin for all but one case. The accuracy of SATB2 was confirmed in the expansion cohort (91.5%). SATB2 expression was also detected in 15% of ovarian endometrioid carcinoma but less than 5% of other ovarian histotypes. A simple two marker combination of CK7 and SATB2 can distinguish lower gastrointestinal from ovarian primary mucinous tumors with greater than 95% accuracy. PAX8 and CDX2 have value as second-line markers. The utility of CK20 in this setting is low and this warrants replacement of this marker with SATB2 in clinical practice.

Introduction Late complications related to enteral tube feeding are little documented in the literature. One 10 year study reports a longitudinal rate of displacement of up to 12%1. Here we investigate the hidden burden of community enteral tube feeding on the Emergency Department (ED). Method We undertook a retrospective review of attendances to the emergency department of the district general hospital in Wolverhampton with gastrostomy and jejunostomy tube complications. ED discharge coding was reviewed over an 18 month period to identify patients attending ED with a gastrostomy or jejunostomy tube. Electronic medical records were then reviewed to determine if the primary reason for attendance was related to the enteral feeding tube. Results In an 18 month period 139 attendances were recorded, 56% of cases were male patients. Fifty patients came from nursing homes, 8 from residential homes, 2 from another hospital and 79 (57%) from their own homes. One hundred and nine were completely dependent on the enteral tube for all nutrition and hydration, 8 required it for fluids only, 2 for nutrition only and 20 were not completely dependent on the enteral tube. The type of tube prompting attendance is shown in table 1 (PEG = percutaneous endoscopic gastrostomy, RIG= radiologically inserted gastrostomy, J= jejunostomy, BGT = balloon gastrostomy tube) The problems causing the ED attendance are shown in table 2. Where in hours was defined as 9–5 Monday to Friday and all other times were defined as out of hours 57 attending during standard working hours of the nutrition support team and 82 attended when the support team were not available, out of hours. Conclusion Using current tariffs the cost of the attendances to ED are £29,000 over the analysed period, with a significant proportion of patients coming from their own home and 60% out of hours. More work on education and supporting carers to resolve problems themselves could reduce the burden on busy EDs.

Introduction The rates of inflammatory bowel disease (IBD) amongst the British South Asian (SA) populations is growing, with some evidence indicating British SA are disproportionally more likely to suffer from IBD than White European. There is a limited understanding of the experience of SA women with IBD, where high rates of infertility, voluntary childlessness and fewer children are common compared to the general population. The objective of this study is to explore how South Asian women with IBD experience living with their chronic illness within dominant SA culture, where childbearing and parenthood are considered culturally mandatory. Methods A qualitative methodology was adopted using Critical Discursive Psychology (CDP). A total of eight SA women, aged between 19–50, were recruited through two IBD clinics in West Midlands hospitals. Unstructured one to one interviews were audio recorded and analysed using CDP methods. Results Data analysis revealed that SA culture and IBD is seen as a hindrance to female worth, marriage and parenthood prospects. Further, there is a limited awareness of IBD that leads to secrecy and stigmatisation. Many SA women find coping with IBD difficult due to the perceived stigma regarding IBD and ‘disease’, lack of understanding about IBD (by patients before diagnosis, family and wider community), pressures regarding cultural mandatory marriage and parenthood, and the role of food (particularly spicy food) in health and illness. Conclusion This study has shown how IBD in SA women create significant personal and social challenges, which deviates from normative expectations of women in this community. It has raised awareness of the emotional and social impact of IBD, which is critical for service provision that suitably meets the needs of this population. This study has highlighted the need for sensitive and culturally-appropriate intervention for SA patients with IBD.

BackgroundThe impact of COVID-19 on pregnant inflammatory bowel disease (IBD) patients is currently unknown. Reconfiguration of services during the pandemic may negatively affect medical and obstetric care. We aimed to examine the impacts on IBD antenatal care and pregnancy outcomes.MethodsRetrospective data were recorded in consecutive patients attending for IBD antenatal care including outpatient appointments, infusion unit visits and advice line encounters.ResultsWe included 244 pregnant women with IBD, of which 75 (30.7%) were on biologics in whom the treatment was stopped in 29.3% at a median 28 weeks gestation. In addition, 9% of patients were on corticosteroids and 21.5% continued on thiopurines. The care provided during 460 patient encounters was not affected by the pandemic in 94.1% but 68.2% were performed via telephone (compared with 3% prepandemic practice; pConclusionIBD antenatal care adjustments during the COVID-19 pandemic have not negatively affected patient care. Despite high levels of immunosuppression, only a single COVID-19 infection occurred. Adverse pregnancy outcomes were infrequent.

Objective We previously reported a pilot randomized controlled trial in gynecologic cancer survivors (GCS) suggesting that wall climbing is safe, feasible, and improves objective physical functioning. Here, we report the effects of wall climbing on posttraumatic growth, quality of life, and symptoms. Methods GCS (N = 35) were randomized to either an 8-week wall climbing intervention (WCI; n = 24) or usual care (UC; n = 11). The primary efficacy outcome was posttraumatic growth assessed by the Posttraumatic Growth Inventory. Secondary outcomes included health-related quality of life assessed by the Short Form-36 (SF-36). Results Analyses of covariance revealed a statistically significant or borderline significant effect favoring WCI over UC for the posttraumatic growth subscales of new possibilities (d = + 0.70; p = 0.065) and personal strength (d = + 0.76; p = 0.049) as well as the SF-36 mental health subscale (d = +0.61; p = 0.077) and the mental health component score (d = +0.80; p = 0.063). Conversely, a statistically significant or borderline significant effect favoring UC over WCI was found for the SF-36 bodily pain subscale (d = −0.50; p = 0.063) and the physical health component score (d = −0.58; p = 0.038). Conclusions This phase I/II study suggests that wall climbing may improve some aspects of posttraumatic growth and mental health in GCS but may also cause some bodily pain and reduced physical health. Larger phase II and III trials are needed to fully describe the potentially complex benefits and harms of wall climbing in GCS.

Aims Lynch syndrome screening in ovarian carcinoma is controversial. The aim of this study was to assess the frequency of deficient mismatch repair (dMMR) protein in a retrospective cohort enriched for non-high-grade serous carcinomas and its association with outcome within histological types. Methods and results Tissue microarrays representing 612 ovarian carcinomas were tested for mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemistry. dMMR was detected in 13.8% of endometrioid and 2.4% of clear cell carcinomas, but not in other histological types. Within endometrioid carcinomas, 11 of 25 dMMR cases showed abnormal MLH1/PMS2, 10 cases showed abnormal MSH2/MSH6, and four cases showed only abnormal MSH6, indicating that at least 7.7% of endometrioid carcinomas have dMMR probably related to Lynch syndrome. The four dMMR clear cell carcinomas showed abnormal MSH2/MSH6 in three cases and only abnormal MSH6 in one case, all probably related to Lynch syndrome. Within endometrioid carcinomas, dMMR was significantly associated with age

Objective Tobacco smoking by cancer patients is associated with increased mortality. Less is known of the impact of smoking on recurrence risk and interaction with chemotherapy treatment. We examined these associations in ovarian cancer. Methods Patients were identified from the Alberta Cancer Registry between 1978 and 2010 and were oversampled for less-common histologic ovarian tumor types. Medical records were abstracted for 678 eligible patients on lifestyle, medical and cancer treatment, and review of pathology slides was performed for 605 patients. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazard models adjusted for age at diagnosis, race, stage and residual disease. Results Among patients receiving adjuvant chemotherapy (N=432), current smoking was significantly associated with shorter duration of overall (OS; HR, 8.56; 95% CI, 1.50–48.7) and progression-free (PFS; HR, 5.74; 95% CI, 1.05–31.4) survival from mucinous ovarian cancer only. There was no significant association between neoadjuvant chemotherapy and survival. However, among patients receiving neoadjuvant chemotherapy (N=44), current smokers had shorter PFS (HR, 4.32; 95% CI, 1.36–13.8; N=32 progressed/9 censored events) compared to never smokers, but the HRs were not statistically different across smoking categories (P interaction=0.87). Conclusions Adverse associations were observed between smoking status and OS or PFS among patients with mucinous ovarian cancer receiving adjuvant chemotherapy. No significant effect was found from neoadjuvant chemotherapy on PFS overall; however, smoking may modify this association. Although needing replication, these findings suggest that patients may benefit from smoking cessation interventions prior to treatment with chemotherapy.

Background Faecal Microbiota Transplant (FMT) has improved outcomes for the treatment of Clostridioides difficile infection (CDI) compared to antibiotic therapy. FMT is classified as a medicinal product in the United Kingdom, similar to the USA and Canada, limiting supply via stool banks without appropriate licencing. In the largest UK cohort to date, we describe the clinical outcomes for 124 patients receiving FMT for recurrent or refractory CDI and present a framework to produce FMT as a licenced medicinal product. Methods Anonymous unrelated healthy donors, screened via health assessment and microbiological testing donated stool. In aerobic conditions FMT aliquots were prepared for immediate use or frozen storage, following a production framework developed to comply with Good Manufacturing Practice. Outcome measures were clinical response to FMT defined as resolution of diarrhoea within seven days and clinical cure defined as response without diarrhoea recurrence at 90 days. Findings Clinical response was 83·9% (95% CI 76·0%–90·0%) after one treatment. Clinical cure was 78·2% (95% CI 67·4%–89·0%) across the cohort. Refractory cases appeared to have a lower initial clinical response rate compared to recurrent cases, however at day 90 there were no differences observed between these groups. Interpretation The methodology developed here enabled successful licencing of FMT by The Medicines and Healthcare products Regulatory Agency as a medicinal product. This has widened the availability of FMT in the National Health Service via a stool bank and can be applied in other centres across the world to improve access to safe and quality assured treatments.

Enhanced recovery pathways have been shown to reduce length of stay without increasing readmission or complications in numerous areas of surgery. Uptake of gynecologic oncology ERAS guidelines has been limited. We describe the effect of ERAS guideline implementation in gynecologic oncology on length of stay, patient outcomes, and economic impact for a province-wide single-payer system.We compared pre- and post-guideline implementation outcomes in consecutive staging and debulking patients at two centers that provide the majority of surgical gynecologic oncology care in Alberta, Canada between March 2016 and April 2017. Clinical outcomes and compliance were obtained using the ERAS Interactive Audit System. Patients were followed until 30 days after discharge. Negative binomial regression was employed to adjust for patient characteristics.We assessed 152 pre-ERAS and 367 post-ERAS implementation patients. Mean compliance with ERAS care elements increased from 56% to 77.0% after implementation (p 0.0001). Median length of stay for all surgeries decreased from 4.0 days to 3.0 days post-ERAS (p 0.0001), which translated to an adjusted LOS decrease of 31.4% (95% CI = [21.7% - 39.9%], p 0.0001). In medium/high complexity surgery median LOS was reduced by 2.0 days (p = 0.0005). Complications prior to discharge decreased from 53.3% to 36.2% post-ERAS (p = 0.0003). There was no significant difference in readmission (p = 0.6159), complications up to 30 days (p = 0.6274), or mortality (p = 0.3618) between the cohorts. The net cost savings per patient was $956 (95%CI: $162 to $1636).Systematic implementation of ERAS gynecologic oncology guidelines across a healthcare system improves patient outcomes and saves resources.

Introduction Thiopurines, through an association with Epstein Barr Virus (EBV), confer an increased risk of GI lymphoma when used to treat Inflammatory Bowel Disease (IBD), with EBV naive individuals carrying a higher risk. Current European Crohn’s and Colitis Organisation (ECCO) guidelines recommend considering EBV screening in individuals prior to initiating immunomodulator therapy. This audit identifies the impact of EBV naive status on subsequent treatment decisions and the resulting cost expenditure at the Royal Wolverhampton NHS Trust (RWHT). Methods We conducted a retrospective analysis of IBD patients undergoing EBV screening between June 2015 and June 2017 and extracted relevant data from electronic records. Results Overall 359 patients underwent EBV screening in the specified period with 43 (12%) patients being identified as EBV naive. The EBV naive sample consisted of 27 (63%) males and 16 (37%) females, with a mean age of 40. Of these 43 patients, 5 were excluded from further analysis as their EBV status was tested for reasons unrelated to IBD management and 4 were excluded as their treatment was altered for reasons other than their EBV status. Table 1 shows the breakdown for the remaining 34. Table 1 Number of patients undergoing EBV screening for initial thiopurine or biologic therapy and the resulting number of patients in whom therapy was switched and the subsequent cost expenditure. *Calculated based on the cost of 12 months of treatment in a 70 kg individual **Patients underwent EBV screening as part of generic pre-screening bloods. Of the 13 individuals who had their therapy switched 8 (62%) were male and 10 (77%) were Caucasian. Conclusions Overall EBV naive status resulted in initiation of therapy different to the initial agent considered in 38% of patients, producing an overall cost expenditure of approximately £1 23 416 with treatment more likely to be switched in male and Caucasian patients. However, the absolute risk of lymphoma remains low and given the cost, the average age of patients being associated with poorer prognosis and increased likelihood of subsequent antibody development to biologic therapy in patients without initial thiopurine treatment, is the practise of EBV screening in IBD management clinically relevant?

Introduction Inflammatory bowel disease (IBD) is a chronic condition that can affect patients during their reproductive years. Previous studies report that IBD patients have high levels of pregnancy-related fears and voluntary childlessness. The aim of this project is to perform a literature review on the psychosocial effects of IBD on patient‘s reproductive health and investigate factors affecting family planning decisions. Method Six electronic databases (CINAHL, PsycInfo, EMBASE, Pubmed, Web of Science, Sciencedirect) were searched using a broad search strategy. Studies using qualitative, quantitative and mixed methods designs were eligible. Results Using Prisma-P, a total of 3600 records were identified through electronic databases, hand searching and contacting authors. After removing duplicates, 1806 titles were screened and 241 abstracts were reviewed. Of these, 79 full text articles were screened and 41 articles have been included. The studies design included cross-sectional surveys, qualitative, mixed methods and non-randomised controlled intervention studies. Synthesis of the data revealed that sexual dysfunction after surgery, specifically ileal pouch–anal anastomosis, is common for female patients. A small minority of female IBD patients do not use contraception and are at ‘risk’ for pregnancy. Knowledge regarding the effects of IBD on pregnancy and fertility is consistently poor and poor knowledge is associated with voluntary childlessness. Many patients report pregnancy-related fears and anxieties including concerns that IBD or medications may harm the baby or lead to a complicated pregnancy. Patients feared transmission of IBD to their offspring, which may lead to voluntary childlessness. Strategies to improve pregnancy and fertility knowledge (e.g., pre-conception counselling) are successful in reducing pregnancy-related anxieties. However, provisions of pre-conception counselling tend to be limited. The literature in this field is associated with a number of limitations including (a) small sample sizes; (b) low response rate for surveys; (c) the use of unstandardised and non-validated questionnaires; (d) few studies have included male samples and ethnic minority groups; and (e) lack of qualitative enquiry and longitudinal follow-up of patients. Conclusion The literature indicates that some patients with IBD experience sexual dysfunction, poor fertility and pregnancy-related knowledge, high levels of pregnancy-related fears, concerns and voluntary childlessness. Intervention to improve knowledge tends to be successful. This review has identified several psychosocial effects of IBD on reproductive health which need further investigation.

Objective To evaluate patient-reported outcomes (PROs) between women treated by laparoscopic, robotic and open approaches for endometrial cancer. Methods Prospective cohort study comparing PRO at baseline, short- (1 and 3 weeks) and long-term (12 and 24 weeks) follow-up postoperatively. Quality of life (QOL) measures were the Functional Assessment of Cancer Therapy (FACT-G), EuroQol Five Dimensions (EQ-5D), and Brief Pain Inventory (BPI). Sexual health measures were the Female Sexual Function Index (FSFI) and the Sexual Adjustment and Body Image Scale for Gynecologic Cancer (SABIS-G). Results 468 eligible patients (laparotomy = 92, laparoscopy = 152, robotic = 224) were recruited. There were no significant differences between the laparoscopy and robotic groups for any PRO ( P > 0.05). At short-term follow-up, patients who underwent minimally invasive surgery (robotic or laparoscopy) had significantly higher FACT-G ( P P P = 0.02) and improved pain interference ( P = 0.0008), than patients undergoing laparotomy. At long-term follow-up, there were sustained improvements in the FACT-G ( P = 0.035) and the health state EQ-5D visual analogue scale ( P = 0.022). Surgical approach had no impact on sexual health ( P > 0.05); however the mean FSFI score for the entire cohort met clinical cut-offs for sexual dysfunction. Conclusion Minimally invasive approaches result in improved QOL beyond the short-term postoperative period, with benefits noted up to 12 weeks after surgery. This prolonged QOL advantage provides further evidence that MIS should be the standard surgical approach for women with early stage endometrial cancer.

Importance Cytotoxic CD8+tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+TILs by histotype and in relation to other clinical factors. Objective To define the prognostic role of CD8+TILs in epithelial ovarian cancer. Design, Setting, and Participants This was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium. More than 5500 patients, including 3196 with high-grade serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650 person-years. Exposures Following immunohistochemical analysis, CD8+TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+TILs per high-powered field: negative (none), low (1-2), moderate (3-19), and high (≥20). CD8+TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines. Main Outcomes and Measures Overall survival time. Results The final sample included 5577 women; mean age at diagnosis was 58.4 years (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the most infiltration. CD8+TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+TILs, respectively (Pvalue for trend = 4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not for those with the other histotypes. Among HGSOCs, CD8+TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germlineBRCA1pathogenic mutation, but were not prognostic forBRCA2mutation carriers. Evaluation of uncategorized CD8+TIL counts showed a near-log-linear functional form. Conclusions and Relevance This study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+TILs and HGSOC survival. That the extent of infiltration is prognostic, not merely its presence or absence, suggests that understanding factors that drive infiltration will be the key to unraveling outcome heterogeneity in this cancer.

This paper aims to validate whether hormone receptor expression is associated with longer survival among women diagnosed with ovarian endometrioid carcinoma (EC), and whether it identifies patients with stage IC/II tumors with excellent outcome that could be spared from toxic chemotherapy. Expression of estrogen receptor (ER) and progesterone receptor (PR) was assessed on 182 EC samples represented on tissue microarrays using the Alberta Ovarian Tumor Type (AOVT) cohort. Statistical analyses were performed to test for associations with ovarian cancer specific survival. ER or PR expression was present in 87.3% and 86.7% of cases, respectively, with co-expression present in 83.0%. Expression of each of the hormonal receptors was significantly higher in low-grade tumors and tumors with squamous differentiation. Expression of ER (Hazard Ratio (HR) = 0.18, 95% confidence interval 0.08–0.42, p = 0.0002) and of PR (HR = 0.22, 95% confidence interval 0.10–0.53, p = 0.0011) were significantly associated with longer ovarian cancer specific survival adjusted for age, grade, treatment center, stage, and residual disease. However, the five-year ovarian cancer specific survival among women with ER positive stage IC/II EC was 89.0% (standard error 3.3%) and for PR positive tumors 89.9% (standard error 3.2%), robustly below the 95% threshold where adjuvant therapy could be avoided. We validated the association of hormone receptor expression with ovarian cancer specific survival independent of standard predictors in an independent sample set of EC. The high ER/PR co-expression frequency and the survival difference support further testing of the efficacy of hormonal therapy in hormone receptor-positive ovarian EC. The clinical utility to identify a group of women diagnosed with EC at stage IC/II that could be spared from adjuvant therapy is limited.

AimsTo prospectively evaluate whether between-assay variability of different faecal calprotectin (f-Cp) assays influences diagnostic accuracy for inflammatory bowel disease (IBD) in a cohort of patients with confirmed IBD and irritable bowel syndrome (IBS). To also evaluate the diagnostic accuracy of faecal S100A12 (f-S100A12) against f-Cp in the same patient cohort and assess whether f-S100A12 offers additional diagnostic value.MethodsF-Cp using four commercially available f-Cp assays, f-S100A12 and blood biomarkers were measured in patients, recruited from the local IBD clinic, who had established IBS or active ulcerative colitis (UC) and Crohn’s disease (CD). Diagnostic sensitivities and specificities for each assay and biomarker were calculated and compared.ResultsMedian f-Cp levels in all assays were significantly higher in UC (347–884 µg/g; n=28) and CD (377–838 µg/g; n=15) compared with IBS (6–27 µg/g; n=17). Sensitivities and specificities at 50 µg/g were 94%–100% and 82%–100%, respectively. Median f-S100A12 levels were significantly higher in UC (81.0 µg/g; IQR 38.3–159.8) and CD (47.2 µg/g; IQR 5.3–108.9) compared with IBS (0.7 µg/g; IQR 0.5–0.8). At 2.8 µg/g, f-S100A12 had a sensitivity of 97% and specificity of 94%. The blood biomarkers demonstrated sensitivities and specificities of 44%–63% and 80%–92%, respectively.ConclusionsThe diagnostic sensitivity of the calprotectin assays was similar despite inter-kit variability in absolute values. There is a need for f-Cp assay standardisation, but in its absence assay-specific cut-off values may optimise their diagnostic performance. F-S100A12 demonstrated comparable sensitivity and specificity to f-Cp and although a research tool at present, may have a future role to play in the diagnosis and management of these patients.

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.

Background: Folate receptor 1 (FOLR1) is expressed in the majority of ovarian carcinomas (OvCa), making it an attractive target for therapy. However, clinical trials testing anti-FOLR1 therapies in OvCa show mixed results and require better understanding of the prognostic relevance of FOLR1 expression. We conducted a large study evaluating FOLR1 expression with survival in different histological types of OvCa. Methods: Tissue microarrays composed of tumour samples from 2801 patients in the Ovarian Tumour Tissue Analysis (OTTA) consortium were assessed for FOLR1 expression by centralised immunohistochemistry. We estimated associations for overall (OS) and progression-free (PFS) survival using adjusted Cox regression models. High-grade serous ovarian carcinomas (HGSC) from The Cancer Genome Atlas (TCGA) were evaluated independently for association between FOLR1 mRNA upregulation and survival. Results: FOLR1 expression ranged from 76% in HGSC to 11% in mucinous carcinomas in OTTA. For HGSC, the association between FOLR1 expression and OS changed significantly during the years following diagnosis in OTTA (Pinteraction=0.01, N=1422) and TCGA (Pinteraction=0.01, N=485). In OTTA, particularly for FIGO stage I/II tumours, patients with FOLR1-positive HGSC showed increased OS during the first 2 years only (hazard ratio=0.44, 95% confidence interval=0.20–0.96) and patients with FOLR1-positive clear cell carcinomas (CCC) showed decreased PFS independent of follow-up time (HR=1.89, 95% CI=1.10–3.25, N=259). In TCGA, FOLR1 mRNA upregulation in HGSC was also associated with increased OS during the first 2 years following diagnosis irrespective of tumour stage (HR: 0.48, 95% CI: 0.25–0.94). Conclusions: FOLR1-positive HGSC tumours were associated with an increased OS in the first 2 years following diagnosis. Patients with FOLR1-negative, poor prognosis HGSC would be unlikely to benefit from anti-FOLR1 therapies. In contrast, a decreased PFS interval was observed for FOLR1-positive CCC. The clinical efficacy of FOLR1-targeted interventions should therefore be evaluated according to histology, stage and time following diagnosis.

Purpose/objectives To examine the feasibility and preliminary efficacy of an eight-week supervised climbing intervention for gynecologic cancer survivors (GCSs). . Design A pilot randomized, controlled trial. . Setting The Wilson Climbing Center in Edmonton, Alberta, Canada. . Sample 35 GCSs who had completed cancer therapy. . Methods GCSs were randomized to an eight-week (16 session) supervised wall climbing intervention (WCI) (n = 24) or usual care (UC) (n = 11). . Main research variables Feasibility outcomes included recruitment rate, adherence rate, skill performance, and safety. Preliminary efficacy outcomes were objective health-related and functional fitness assessed before and after the eight-week intervention using the Senior Fitness Test. . Findings Median adherence to the WCI was 13.5 of 16 sessions. Most GCSs were proficient on 16 of 24 skill assessment items. No serious adverse events were reported. Based on intention-to-treat analyses, the WCI group was superior to the UC group for the 6-minute walk, 30-second chair stand, 30-second arm curls, sit and reach, 8-foot up-and-go, grip strength-right, and grip strength-left assessments. . Conclusions The Gynecologic Cancer Survivors Wall Climbing for Total Health (GROWTH) Trial demonstrated that an eight-week supervised WCI was safe, feasible, and improved functional fitness in GCSs. Phase II and III trials are warranted to further establish the safety, feasibility, and efficacy of WCIs in cancer survivors. . Implications for nursing Oncology nurses may consider a climbing wall as an alternative type of physical activity for improving functional fitness in GCSs.

Nitric oxide (NO) is generated by tumor, stromal and endothelial cells and plays a multifaceted role in tumor biology. Many physiological functions of NO are mediated by soluble guanylyl cyclase (sGC) and NO/sGC signaling has been shown to promote proliferation and survival of ovarian cancer cells. However, how NO/sGC signaling is modulated in ovarian cancer cells has not been studied. The evolutionarily conserved Notch signaling pathway plays an oncogenic role in ovarian cancer. Here, we report that all three ovarian cancer cell lines we examined express a higher level of GUCY1B3 (the β subunit of sGC) compared to non-cancerous immortalized ovarian surface epithelial (IOSE) cell lines. Interestingly, the highest expression of GUCY1B3 in ovarian cancer OVCAR3 cells is concurrent with the expression of Notch3. In IOSE cells, forced activation of Notch3 increases the expression of GUCY1B3, NO-induced cGMP production, and the expression of cGMP-dependent protein kinase (PKG), thereby enhancing NO- and cGMP-induced phosphorylation of vasodilator-stimulated phosphoprotein (VASP, a direct PKG substrate protein). In contrast, inhibition of Notch by DAPT reduces GUCY1B3 expression and NO-induced cGMP production and VASP phosphorylation in OVCAR3 cells. Finally, we confirmed that inhibition of sGC by ODQ decreases growth of ovarian cancer cells. Together, our work demonstrates that Notch is a positive regulator of NO/sGC signaling in IOSE and ovarian cancer cells, providing the first evidence that Notch and NO signaling pathways interact in IOSE and ovarian cancer cells.

Objective Notch3 is implicated in chemoresistance of ovarian cancer, yet the molecular mechanism underlying Notch3-mediated drug resistance remains to be elucidated. Here, we investigated the role of Notch3 in carboplatin-induced apoptosis in ovarian cancer cells. Methods Ovarian cancer cell line OVCA429 cells were stably transduced with an empty vector or a retroviral vector expressing the Notch3 intracellular domain (NICD3, the constitutively active form of Notch3) to generate OVCA429/vector and OVCA429/NICD3 cells. Epithelial–mesenchymal transition (EMT) was determined by morphological change and expression of the EMT markers. Carboplatin-induced cytotoxicity was determined by the neutral red uptake assay. Apoptosis was determined by Annexin V staining and Western blotting. Carboplatin-induced phosphorylation of extracellular signal-regulated kinase (ERK) was identified by a phospho-kinase array and confirmed by Western blotting. Results Activation of Notch3 in OVCA429 cells causes a spindle and fibroblast-like morphology, induces the expression of smooth muscle α-actin, Slug and Snail, but decreases the expression of E-cadherin, indicating that Notch3 activation induces EMT in OVCA429 cells. Furthermore, Notch3 activation renders OVCA429 cells more resistant to carboplatin-induced cytotoxicity and attenuates carboplatin-induced apoptosis in these cells. Our results indicate that phosphorylation of ERK is a positive regulator of carboplatin-induced apoptosis in OVCA429 cells. Interestingly, carboplatin-induced ERK phosphorylation is inhibited by Notch3 activation. Conclusions Notch3 activation induces EMT and attenuates carboplatin-induced apoptosis in OVCA429 cells. ERK phosphorylation plays a pro-apoptotic role in carboplatin-induced apoptosis in OVCA429 cells. Interestingly, Notch3 activation attenuates carboplatin-induced ERK phosphorylation in these cells.

Summary Summary Barrett's oesophagus (BO) and gastro-oesophageal reflux disease (GERD) are precursors of oesophageal adenocarcinoma (OAC). There is an oesophageal biofilm, which changes in disease, but its role in aetiopathogenesis remains unclear. Aim To define the oesophageal microbiota of patients with GERD, BO and OAC compared with controls and to investigate mucosal responses related to the microbiota. Methods Cultural analysis identified the dominant bacterial species from a subset of each disease group. Based on this, molecular techniques were used to define the cohort. Host responses were analysed in tissues and co-culture experiments. Results A total of 111 species belonging to 26 genera were isolated. There was a significant decrease in bacterial counts in the GERD and BO groups for all genera except Campylobacter, which colonised GERD and Barrett's patients in increasing numbers. Campylobacter concisus was the dominant species. This relationship was not seen in the cancer group. Significant increases in IL-18 were seen in GERD and BO colonised by Campylobacter. Conclusions This study defines differences in the oesophageal biofilm in disease states, revealing the emergence of C. concisus as the dominant new colonist in the refluxed oesophagus. We also associate the presence of these bacteria with increased expression of cytokines related to carcinogenesis.

Mucinous ovarian carcinomas (MCs) typically do not respond to current conventional therapy. We have previously demonstrated amplification of HER2 in 6 of 33 (18.2%) mucinous ovarian carcinomas (MCs) and presented anecdotal evidence of response with HER2-targeted treatment in a small series of women with recurrent HER2-amplified (HER2+) MC. Here, we explore HER2 amplification and KRAS mutation status in an independent cohort of 189 MCs and 199 mucinous borderline ovarian tumours (MBOTs) and their association to clinicopathological features. HER2 status was assessed by immunohistochemistry (IHC), FISH, and CISH, and interpreted per ASCO/CAP guidelines, with intratumoural heterogeneity assessment on full sections, where available. KRAS mutation testing was performed with Sanger sequencing. Stage and grade were associated with recurrence on both univariate and multivariate analysis (p < 0.001). Assessment of HER2 status revealed overexpression/amplification of HER2 in 29/154 (18.8%) MCs and 11/176 (6.2%) MBOTs. There was excellent agreement between IHC, FISH, and CISH assessment of HER2 status (perfect concordance of HER2 0 or 1+ IHC with non-amplified status, and 3+ IHC with amplified status). KRAS mutations were seen in 31/71 (43.6%) MCs and 26/33 (78.8%) MBOTs, and were near mutually exclusive of HER2 amplification. In the 189 MC cases, a total of 54 recurrences and 59 deaths (53 of progressive disease) were observed. Within MCs, either HER2 amplification/overexpression or KRAS mutation was associated with decreased likelihood of disease recurrence (p = 0.019) or death (p = 0.0041) when compared to cases with neither feature. Intratumoural heterogeneity was noted in 26% of HER2-overexpressing cases. These data support the stratification of MCs for the testing of new treatments, with HER2-targeted therapy as a viable option for HER2+ advanced or recurrent disease. Further research is required to delineate the molecular and clinical features of the ∼34% of MC cases with neither HER2 amplification nor KRAS mutations.

Background and aims Complication rates of Roux-en-Y gastric bypass (RYGB) vary from centre to centre, but anastomotic stricture is the commonest, and is managed in the majority by endoscopic pneumatic dilatation. The aim of this study was to assess the endoscopic burden of RYGB surgery. Patients and methods All patients undergoing RYGB surgery over a 29-month period were included and were followed-up retrospectively and prospectively for a minimum of 180 days to monitor for endoscopic procedures performed in relation to the RYGB at Walsall Manor Hospital, UK. Five hundred and fifty-three patients underwent RYGB surgery during the study period. Results One hundred and thirteen patients had 147 endoscopic procedures, including 65 pneumatic dilatations, at a cost to the NHS of £58 077 over a 29-month study period, with an average cost of £2003 a month. or £105 per RYGB operation performed. The anastomotic stricture rate for the group was 11.39%. The complication rate for dilatation of anastomotic strictures was 0%. Conclusions RYGB anastomotic strictures can be safely managed by dilatation. If bariatric surgery is performed locally, then endoscopy departments must expect to factor in, not only the burden of dealing with actual complications, but also the burden of investigating for potential complications.

Contains fulltext : 174140.pdf (Publisher’s version ) (Closed access) PURPOSE: Survival following ovarian cancer diagnosis is generally low; understanding factors related to prognosis could be important to optimize treatment. The role of previously diagnosed comorbidities and use of medications for those conditions in relation to prognosis for ovarian cancer patients has not been studied extensively, particularly according to histological subtype. METHODS: Using pooled data from fifteen studies participating in the Ovarian Cancer Association Consortium, we examined the associations between history of hypertension, heart disease, diabetes, and medications taken for these conditions and overall survival (OS) and progression-free survival (PFS) among patients diagnosed with invasive epithelial ovarian carcinoma. We used Cox proportional hazards regression models adjusted for age and stage to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) overall and within strata of histological subtypes. RESULTS: History of diabetes was associated with increased risk of mortality (n = 7,674; HR = 1.12; 95% CI = 1.01-1.25). No significant mortality associations were observed for hypertension (n = 6,482; HR = 0.95; 95% CI = 0.88-1.02) or heart disease (n = 4,252; HR = 1.05; 95% CI = 0.87-1.27). No association of these comorbidities was found with PFS in the overall study population. However, among patients with endometrioid tumors, hypertension was associated with lower risk of progression (n = 339, HR = 0.54; 95% CI = 0.35-0.84). Comorbidity was not associated with OS or PFS for any of the other histological subtypes. Ever use of beta blockers, oral antidiabetic medications, and insulin was associated with increased mortality, HR = 1.20; 95% CI = 1.03-1.40, HR = 1.28; 95% CI = 1.05-1.55, and HR = 1.63; 95% CI = 1.20-2.20, respectively. Ever use of diuretics was inversely associated with mortality, HR = 0.71; 95% CI = 0.53-0.94. CONCLUSIONS: Histories of hypertension, diabetes, and use of diuretics, beta blockers, insulin, and oral antidiabetic medications may influence the survival of ovarian cancer patients. Understanding mechanisms for these observations could provide insight regarding treatment.

Background: Combined oral contraceptive (COC) use reduces epithelial ovarian cancer (EOC) risk. However, little is known about risk with COC use before the first full-term pregnancy (FFTP). Methods: This Canadian population-based case–control study (2001–2012) included 854 invasive cases/2139 controls aged ⩾40 years who were parous and had information on COC use. We estimated odds ratios (aORs) and 95% confidence intervals (CI) adjusted for study site, age, parity, breastfeeding, age at FFTP, familial breast/ovarian cancer, tubal ligation, and body mass. Results: Among parous women, per year of COC use exclusively before the FFTP was associated with a 9% risk reduction (95% CI=0.86–0.96). Results were similar for high-grade serous and endometrioid/clear cell EOC. In contrast, per year of use exclusively after the FFTP was not associated with risk (aOR=0.98, 95% CI=0.95–1.02). Conclusions: Combined oral contraceptive use before the FFTP may provide a risk reduction that remains for many years, informing possible prevention strategies.

Background This study aimed to assess the endoscopic burden of bariatric surgical procedures at our trust. This is an enhanced parallel study to “The Hidden Endoscopic burden of Roux-en-Y Gastric Bypass” published in Frontline Gastroenterology in 2013 incorporating the data for sleeve gastrectomy and comparison with Roux-en-Y gastric bypass (RYGB). Methods This is a retrospective study that included 211 patients undergoing sleeve gastrectomy over a 34-month period. We utilized previously collected data for the RYGB patient cohort which included 553 patients over a 29-month period. We searched our hospital endoscopic database for patients who underwent post-operative endoscopy for indications related to their surgery. Results 16.6% of the sleeve gastrectomy patients required post-operative endoscopy, of whom 11.4% underwent therapeutic procedures. This compares to 20.4% of the RYGB cohort of whom 50.4% needed therapeutic procedures (P

Objective The objective of this study is to examine the outcomes of combined chemotherapy using methotrexate and dactinomycin in the management of women with low-risk gestational trophoblastic neoplasia (GTN). The primary outcome is the total number of cycles of chemotherapy required to achieve a normal level of human chorionic gonadotropin (hCG). The secondary outcome is treatment-related toxicity. Methods A retrospective chart review of all patients with GTN treated between 1996–2007 and 1991–2007 was performed at the Alberta Cross Cancer Institute and the British Columbia Cancer Agency, respectively. Patients with low-risk GTN, treated with 0.6mg/m 2 dactinomycin (days 1 and 2) and methotrexate 100mg/m 2 were included. Toxicities were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events. The number of cycles to achieve normalization of hCG was determined, and multivariate analyses were performed to identify factors associated with treatment duration. Results One hundred women were eligible. The average age was 29years (range 15–46). The median number of cycles to achieve a normal hCG was 3 (range 1–11). Two patients required second-line treatment and one patient chose to proceed with hysterectomy. Ninety-eight percent of patients were primarily cured with this regimen, and 2 were cured with second line treatment. Grade 3 and 4 hematologic toxicities were experienced by 12% and 8% of patients, respectively. Grade 2 and 3 stomatitis or mucositis were noted in 44% and 3% of patients, respectively. Conclusions Low-risk GTN is reliably and rapidly cured with combined methotrexate–dactinomycin. Toxicity is modest.

Sepsis is common in liver cirrhosis, and animal studies have shown the gut to be the principal source of infection, through bacterial overgrowth and translocation in the small bowel. A total of 33 patients were recruited into this study, 10 without cirrhosis and 23 with cirrhotic liver disease. Six distal duodenal biopsies were obtained and snap frozen for RNA and DNA extraction, or frozen for FISH. Peripheral venous bloods were obtained from 30 patients, including 17 chronic liver disease patients. Samples were analysed by real-time PCR, to assess total bacteria, bifidobacteria, bacteroides, enterobacteria, staphylococci, streptococci, lactobacilli, enterococci, Helicobacter pylori and moraxella, as well as TNF-α, IL-8 and IL-18. There was no evidence of bacterial overgrowth with respect to any of the individual bacterial groups, with the exception of enterococci, which were present in higher numbers in cirrhotic patients (P = 0.04). There were no significant differences in any of the cytokines compared to the controls. The small intestinal mucosal microbiota in cirrhotic patients was qualitatively and quantitatively normal, and this shifts the focus of disease aetiology to factors that reduce gut integrity, failure of mechanisms to remove translocating bacteria, or the large bowel as the source of sepsis.

Endometrial cancer generally presents as early and resectable disease, but about 20% of patients present with either incurable or recurrent/metastatic disease. Patients with good performance status will be treated with hormonal agents, including progestins and tamoxifen, followed by cytotoxic chemotherapy. The options are restricted to hormonal agents for those with multiple comorbidities and older age. Therefore, there is a need to identify novel hormonal agents and other targeted therapeutics with improved therapeutic window in this setting.Clinical trials of letrozole in localized and metastatic settings are reviewed. In the localized setting, limited by the small sample size, preliminary and conflicting clinical activities were observed. Despite the selection of Type I endometrial cancer, which is more estrogen-dependent for its growth, modest clinical activity was observed in the metastatic setting. Thus far, no biomarkers for efficacy have been identified.Further understanding of the relevance of aromatase and estrogen receptor and their interplay with other growth pathways will be necessary to guide further development of letrozole. It is premature to declare letrozole a therapeutic option in recurrent/metastatic endometrial cancer.

Aliment Pharmacol Ther 2010; 32: 872–883 Summary Background Crohn’s disease is an inflammatory illness in which the immune response against gut microorganisms is believed to drive an abnormal immune response. Consequently, modification of mucosal bacterial communities, and the immune effects they elicit, might be used to modify the disease state. Aim To investigate the effects of synbiotic consumption on disease processes in patients with Crohn's disease. Methods A randomized, double-blind placebo-controlled trial was conducted involving 35 patients with active Crohn's disease, using a synbiotic comprising Bifidobacterium longum and Synergy 1. Clinical status was scored and rectal biopsies were collected at the start, and at 3- and 6-month intervals. Transcription levels of immune markers and mucosal bacterial 16S rRNA gene copy numbers were quantified using real-time PCR. Results Significant improvements in clinical outcomes occurred with synbiotic consumption, with reductions in both Crohn's disease activity indices (P = 0.020) and histological scores (P = 0.018). The synbiotic had little effect on mucosal IL-18, INF-γ and IL-1β; however, significant reductions occurred in TNF-α expression in synbiotic patients at 3 months (P = 0.041), although not at 6 months. Mucosal bifidobacteria proliferated in synbiotic patients. Conclusion Synbiotic consumption was effective in improving clinical symptoms in patients with active Crohn's disease.

Chemoresistance renders current chemotherapy regimens ineffective against advanced epithelial ovarian cancer (EOC). Carboplatin (the first-line chemotherapeutic agent to treat EOC) induces cell death by regulating multiple signaling pathways. The objective of this study is to identify the signaling pathways that contribute to carboplatin resistance in EOC. To this end, we performed a proteome profiler human phospho-kinase array experiment and compared the phosphorylation profiles between the cisplatin-sensitive A2780s versus its derivative cisplatin-resistant A2780cp cells. The phospho-kinase array revealed that A2780s and A2780cp cells displayed different profiles in basal and carboplatin-induced phosphorylation. Phosphorylation of p38 MAPK was increased by carboplatin more markedly in A2780s cells compared to A2780cp cells. Inhibition of p38 MAPK activity by its specific inhibitor SB203580 increased resistance to carboplatin in A2780cp cells, but not in A2780s cells or in ascites-derived high-grade serous EOC cells. Interestingly, SB203580 increased the number of viable cells in the primary EOC cells, which was concomitant with an increase in survivin expression. In conclusion, inhibition of p38 MAPK by SB203580 increases resistance to carboplatin in A2780cp cells and the number of viable cells in the primary EOC cells, suggesting that pharmacological inhibition of p38 MAPK might not be an effective therapeutic strategy for EOC.

Background & Aims The incidence of Crohn's disease (CD) in northeastern Scotland was last reported as rising in the 1980's, while in the rest of Europe it had reached steady state. This study reviewed the incidence of CD in NHS Tayside. Methods Data was collected retrospectively and analysed using age and sex standardization, socioeconomic factors and urban and rural postcodes. Results A point prevalence of 157 per 100,000 population in the Tayside region was found. The average incidence of CD was 9.56 per 100,000 per year between 2003 and 2007 and 7.16 per 100,000 per year between 1998 and 2001. There was no link to urbanization and no difference in incidence between the sexes. Incidence was not related to affluence in this population and peak age of onset occurred in the third decade of life only. 12.7% of patients had a family history of inflammatory bowel disease and 25% of patients were current smokers. Conclusions The incidence of CD appears to have arrived at a steady state in Tayside, while recent evidence suggests that it is on the rise in Scandinavia again. The results of the genetic studies to come from the east of Scotland are eagerly awaited to help shed light on the aetiology of this complex disorder.

Crohn's disease and ulcerative colitis are the two principal forms of inflammatory bowel disease (IBD). The root causes of these chronic and acute immunological disorders are unclear, but intestinal microorganisms are known to play a key role in the initiation and maintenance of disease. However, at present, there is no clear evidence for a single transmissible agent being involved in IBD aetiology. Although marked alterations occur in faecal and mucosal bacterial communities in IBD, it is unclear whether they are responsible for causing disease, or are due to changes in the gut environment that result from inflammatory reactions and extensive tissue destruction. Despite the involvement of microorganisms in inflammatory processes, antibiotic therapy has generally been unsuccessful in IBD. However, recent studies involving the use of probiotics, prebiotics and synbiotics suggest that there is potential for controlling these diseases through manipulation of the composition of the gut microbiota, and direct interactions with the gut immune system.

Objective: Regular physical activity is positively associated with quality of life in ovarian cancer survivors, but no data exist on how best to promote activity in this population. This study investigated the interests and preferences of ovarian cancer survivors with regard to physical activity participation. Methods: A provincial, population-based postal survey of ovarian cancer survivors in Alberta, Canada, was performed including measures of self-reported physical activity, medical and demographic variables, and physical activity preferences. Results: A total of 359 women participated (51.4% response rate). Over half expressed interest in participating in a physical activity program (53.8%), with a further 32.9% maybe interested. The most common preferences were for programs to be home-based (48.9%), start post-treatment (69.5%), and involve walking (62.7%). There were differences in preferences based on demographic, but not medical, factors. Conclusion: The majority of ovarian cancer survivors expressed interest in participating in physical activity programs; however, some preferences varied by demographic factors. Designing physical activity interventions according to these preferences may optimize adherence and outcomes in ovarian cancer survivors. Copyright © 2009 John Wiley & Sons, Ltd.

Crohn's disease (CD) and ulcerative colitis (UC) are the two principal forms of inflammatory bowel disease (IBD). Animal studies show that bacteria are involved in the etiology of IBD, and much is now known about the inflammatory processes associated with CD and UC, as well as the underlying genetic, environmental, and lifestyle issues that can affect an individual's predisposition to these diseases. However, while a number of candidate microorganisms have been put forward as causative factors in IBD, the primary etiologic agents are unknown. This review discusses the potential role of luminal and mucosal microbial communities in the etiology of IBD, and outlines studies that have been made using a variety of biotherapeutic therapies, involving the use of antibiotics, probiotics, prebiotics, and synbiotics.

Lower urinary tract dysfunction is a common morbidity related to radical hysterectomy (RAH). Although transurethral catheterization (TUC) has traditionally been used for postoperative bladder drainage following RAH, suprapubic catheterization (SPC) is an alternative method that may be advantageous.To determine, by means of a retrospective cohort study, the incidence of urinary tract infection (UTI), duration of postoperative hospital stay, and time to trial of voiding in women catheterized suprapubically or transurethrally after RAH for early stage cervical cancer.Two hundred twelve patients who underwent RAH and staging for stage IA1 + LVS, 1A2, and 1B1 cancer of the cervix in Edmonton between 1996 and 2006 were included in the study. Three gynaecologic oncologists performed the surgeries. Operative, postoperative, and demographic data were extracted from patient records. Patients were catheterized either suprapubically (SPC group) or transurethrally (TUC group) according to the surgeon's discretion. Comparative tests and multivariate regression analysis were used to compare outcome measures between the groups and to adjust for confounding variables.The TUC group had a higher proportion of patients with UTI (27%) than the SPC group (6%) (P0.001). The SPC group had a shorter postoperative hospital stay (4.8 vs. 5.7 days; P0.001) and an earlier trial of voiding (2.7 vs. 4.4 days; P0. 001). Following regression analysis, statistically significant differences remained for UTI and time to initiation of a trial of voiding.After RAH for early stage cervical cancer, suprapubic catheterization is associated with a lower rate of UTI and an earlier trial of voiding than transurethral catheterization.

The normal colonic microflora is intimately involved in the aetiology of inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). These conditions are often refractile to conventional treatments involving the employment of anti-inflammatory and immunosuppressant drugs, and this has led to a search for alternative therapies based on the use of probiotics, prebiotics and synbiotics. The majority of investigations in this area have been done with probiotics, and while there is increasing interest in the abilities of prebiotics and synbiotics to control the symptoms of IBD, very few randomised controlled trials have been reported. Although the results have been variable, human and animal studies have demonstrated that in many circumstances, these functional foods can alter the composition of the colonic microbiota, reduce inflammatory processes in the gut mucosa, and have the potential to induce disease remission. More work is needed to understand the effects of prebiotics and synbiotics on microbial communities in the gut, and their interactions with the host's immune system.