Heart failure as a serious complication of iodinated contrast-induced hyperthyroidism: case-report.

BACKGROUND: exposure to iodinated contrast media (ICM) can cause hyperthyroidism, due to disruption of thyroid hormone regulation. Although rare, it can have severe consequences and can lead to fatal complications. Current guidelines do not recommend standard laboratory testing of the thyroid function prior to ICM exposure. Prophylactic treatment of patients at higher risk of hyperthyroidism is not advised. CASE PRESENTATION: we report the case of an 82-year-old woman who developed ICM induced hyperthyroidism after undergoing a chest computed tomography (CT). One month after ICM administration she presented with pneumonia at the emergency department. Hyperthyroidism was found with concomitant tachycardia, which was hard to control. As a result of hyperthyroidism and coincidental pneumonia the patient developed heart failure and died of myocardial ischemia. CONCLUSIONS: this case report underlines the importance of close monitoring of high-risk patients after ICM exposure. Clinicians should be aware of the risk of hyperthyroidism and potential severe complications. The use of ICM needs careful consideration, especially in the elderly who suffer more often from multinodular goitre.

Colonoscopy in the very elderly.

Introduction: Colonoscopy is the gold standard test for investigating lower gastrointestinal symptoms and is an important therapeutic tool for colonic polypectomy. This paper is aimed at the general physician and examines the role of colonoscopy in very elderly patients by exploring the particular risks in this population, the yield of colonoscopy and potential alternative investigations. Sources of data: Original research and review articles were identified through selective PubMed searches. Guidelines were identified through interrogation of national and international society websites in addition to PubMed searches. Areas of agreement: Advanced age alone is not a reason to avoid investigation. The decision to perform colonoscopy in this population must take into account indication and yield, risks of the procedure and bowel preparation, physical fitness of the patient, potential alternative and the ability to consent. As a general rule, the principle of 'first doing no harm' should be applied and requires balancing of the risks of the procedure and preparation with the benefits of doing the test. Areas of controversy: There is no defined upper age limit at which colonoscopy is contraindicated, however; the National Health Service Bowel Cancer Screening Programme stops inviting patients for screening and surveillance colonoscopy at age 75. Growing points and areas timely for developing research: The concepts of 'first do no harm' and shared decision-making are not new but are increasingly important, particularly in this patient group. It is crucial to provide patients with information about risks, benefits and alternative investigations to empower their decision-making.

Scottish Bowel Screening Programme colonoscopy quality - scope for improvement?

AIM: The delivery of the Scottish Bowel Screening Programme (SBoSP) is rooted in the provision of a high quality, effective and participant-centred service. Safe and effective colonoscopy forms an integral part of the process. Additional accreditation as part of a multi-faceted programme for participating colonoscopists, as in England, does not exist in Scotland. This study aimed to describe the quality of colonoscopy in the SBoSP and compare this to the English national screening standards. METHODS: Data were collected from the SBoSP between 2007 and 2014. End-points for analysis were caecal intubation, cancer, polyp and adenoma detection, and complications. Overall results were compared with 2012 published English national standards for screening and outcomes from 2006 to 2009. RESULTS: During the study period 53 332 participants attended for colonoscopy. The colonoscopy completion rate was 95.6% overall. The mean cancer detection rate was 7.1%, the polyp detection rate was 45.7% and the adenoma detection rate was 35.5%. The overall complication rate was 0.47%. CONCLUSION: Colonoscopy quality in the SBoSP has exceeded the standard set for screening colonoscopy in England, despite not adopting a multi-faceted programme for screening colonoscopy. However, the overall adenoma detection rate in Scotland was 9.1% lower than that in England which has implications for colonoscopy quality and may have an impact on cancer prevention rates, a key aim of the SBoSP.

Exploring the influence of context on feedback at medical school: a video-ethnography study.

Feedback in medical education is complicated by the multiple contexts within which learning occurs. However, feedback research in medical education has typically focused on information provided by tutors to students with limited exploration of the influence of context. This research seeks to address this gap by exploring the influence of multiple contexts upon feedback processes. Employing video-ethnography methodology we explored feedback in two common contexts for medical student learning: the simulated clinical environment and the medical workplace. Learning and teaching sessions were filmed in each of these contexts, capturing diverse feedback processes. Data were analysed for key themes using a Framework Analysis approach and similarities and differences between the two contexts identified. In total 239 distinct feedback episodes across 28 different teaching and learning sessions were captured, with feedback processes relating to the patient, practice, educational and institutional contexts observed. In this paper, we concentrate on key similarities and differences in feedback processes between the two contexts with respect to six themes: feedback interlocutors, interlocutor positioning, feedback types, feedback foci, feedback styles and feedback milieu. We argue that feedback is inextricably linked to the multiple contexts in which feedback is enacted. It is only by exploring these contextual influences that feedback can be understood more fully. With such understanding we should be better placed to develop interventions capable of improving the long elusive experience of successful feedback.

Exploring trainer and trainee emotional talk in narratives about workplace-based feedback processes.

Emotion characterises learners' feedback experiences. While the failure-to-fail literature suggests that emotion may be important, little is known about the role of emotion for educators. Secondary analyses were therefore conducted on data exploring 110 trainers' and trainees' feedback experiences. Group and individual narrative interviews were conducted across three UK sites. We analysed 333 narratives for emotional talk using textual analysis: Linguistic Inquiry and Word Count. Furthermore, thematic framework analysis was conducted on the trainer narratives to explore aspects of feedback processes that are emotional. An additional in-depth little 'd' discourse analysis was conducted on selected trainer narratives to enable us to explore the complex relationship between the whats (reported events) and the hows (emotional talk). Trainer narratives did not differ significantly in positive or negative emotional talk from trainee narratives. By exploring the interplay of the whats and the hows, several aspects of feedback processes were identified as potentially emotional for trainers including trainers being concerned about upsetting learners and worried about patient safety. This was illustrated through numerous linguistic devices to establish emotional tone such as metaphoric talk and laughter. These findings suggest that feedback processes can be emotional for trainers. It highlights the need to better understand the 'filter' of emotion for trainers but also to better understand how emotion plays a role in feedback as a complex social process.

Detection rate of serrated polyps and serrated polyposis syndrome in colorectal cancer screening cohorts: a European overview.

OBJECTIVE: The role of serrated polyps (SPs) as colorectal cancer precursor is increasingly recognised. However, the true prevalence SPs is largely unknown. We aimed to evaluate the detection rate of SPs subtypes as well as serrated polyposis syndrome (SPS) among European screening cohorts. METHODS: Prospectively collected screening cohorts of ≥1000 individuals were eligible for inclusion. Colonoscopies performed before 2009 and/or in individuals aged below 50 were excluded. Rate of SPs was assessed, categorised for histology, location and size. Age-sex-standardised number needed to screen (NNS) to detect SPs were calculated. Rate of SPS was assessed in cohorts with known colonoscopy follow-up data. Clinically relevant SPs (regarded as a separate entity) were defined as SPs ≥10 mm and/or SPs >5 mm in the proximal colon. RESULTS: Three faecal occult blood test (FOBT) screening cohorts and two primary colonoscopy screening cohorts (range 1.426-205.949 individuals) were included. Rate of SPs ranged between 15.1% and 27.2% (median 19.5%), of sessile serrated polyps between 2.2% and 4.8% (median 3.3%) and of clinically relevant SPs between 2.1% and 7.8% (median 4.6%). Rate of SPs was similar in FOBT-based cohorts as in colonoscopy screening cohorts. No apparent association between the rate of SP and gender or age was shown. Rate of SPS ranged from 0% to 0.5%, which increased to 0.4% to 0.8% after follow-up colonoscopy. CONCLUSIONS: The detection rate of SPs is variable among screening cohorts, and standards for reporting, detection and histopathological assessment should be established. The median rate, as found in this study, may contribute to define uniform minimum standards for males and females between 50 and 75 years of age.

Expanding the Klebsiella pneumoniae volatile metabolome using advanced analytical instrumentation for the detection of novel metabolites.

AIMS: The purpose of this study was to identify the volatile molecules produced by the pathogenic Gram-negative bacterium Klebsiella pneumoniae (ATCC 13883) during in vitro growth using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS). METHODS AND RESULTS: Klebsiella pneumoniae ATCC 13883 was incubated in lysogeny broth to mid-exponential and stationary growth phases. Headspace volatile molecules from culture supernatants were concentrated using solid-phase microextraction (SPME) and analysed via GC×GC-TOFMS. Ninety-two K. pneumoniae-associated volatile molecules were detected, of which 78 (85%) were detected at both phases of growth and 14 (15%) were detected at either mid-exponential or stationary growth phases. CONCLUSIONS: This study has increased the total number of reported K. pneumoniae-associated volatile molecules from 77 to 150, demonstrating the sensitivity and resolution achieved by employing GC×GC-TOFMS for the analysis of bacterial headspace volatiles. SIGNIFICANCE AND IMPACT OF THE STUDY: This study represents an early-stage comprehensive volatile metabolomic analysis of an opportunistic bacterial pathogen. Characterizing the volatile molecules produced by K. pneumoniae during in vitro growth could provide us with a better understanding of this organisms' metabolism, an area that has not been extensively studied to date.

Alcohol purchasing by ill heavy drinkers; cheap alcohol is no single commodity.

OBJECTIVES: Potential strategies to address alcohol misuse remain contentious. We aim to characterise the drink purchases of one population group: heavy drinkers in contact with Scottish health services. We contrast our findings with national sales data and explore the impact of socio-economic status on purchasing behaviour. STUDY DESIGN: Cross-sectional study comparing alcohol purchasing and consumption by heavy drinkers in Edinburgh and Glasgow during 2012. METHODS: 639 patients with serious health problems linked to alcohol (recruited within NHS hospital clinics (in- and out-patient settings) 345 in Glasgow, 294 in Edinburgh) responded to a questionnaire documenting demographic data and last week's or a 'typical' weekly consumption (type, brand, volume, price, place of purchase). Scottish Index of Multiple Deprivation quintile was derived as proxy of sociodemographic status. RESULTS: Median consumption was 184.8 (IQR = 162.2) UK units/week paying a mean of 39.7 pence per alcohol unit (£0.397). Off-sales accounted for 95% of purchases with 85% of those <50 pence (£0.5 UK) per alcohol unit. Corresponding figures for the Scottish population are 69% and 60%. The most popular low-priced drinks were white cider, beer and vodka with the most common off-sales outlet being the corner shop, despite supermarkets offering cheaper options. Consumption levels of the cheapest drink (white cider) were similar across all quintiles apart from the least deprived. CONCLUSIONS: Heavy drinkers from all quintiles purchase the majority of their drinks from off-sale settings seeking the cheapest drinks, often favouring local suppliers. While beer was popular, recent legislation impacting on the sale of multibuys may prevent the heaviest drinkers benefiting from the lower beer prices available in supermarkets. Non-etheless, drinkers were able to offset higher unit prices with cheaper drink types and maintain high levels of consumption. Whilst price is key, heavy drinkers are influenced by other factors and adapt their purchasing as necessary.

Workplace abuse narratives from dentistry, nursing, pharmacy and physiotherapy students: a multi-school qualitative study.

INTRODUCTION: Previous healthcare student abuse research typically employs quantitative surveys that fail to explore contributory factors for abuse and students' action in the face of abuse. Following a recent qualitative study of medical students' abuse narratives, the current study explores dental, nursing, pharmacy and physiotherapy students' abuse narratives to better understand healthcare workplace abuse. METHODS: We conducted three individual and 11 group interviews with 69 healthcare students in three Universities to elicit professionalism dilemma narratives. Of 226 professionalism dilemmas elicited, 79 were coded as student abuse. Secondary-level thematic analysis of the abuse narratives addressed the following questions: What types of abuse experiences do healthcare students narrate? What factors do they cite as contributing to abuse and their responses to abuse? RESULTS: Healthcare students reported mostly covert abuse in their narratives. Although narrators described individual, relational, work and organisational factors contributing to abuse, they mostly cited factors relating to perpetrators. Most participants stated that they acted in the face of their abuse, and they mostly cited factors relating to themselves for acting. Students who did nothing in the face of abuse typically cited the perpetrator-recipient relationship as the main contributory factor. DISCUSSION: There are many similarities across the narratives of the five healthcare student groups, suggesting that complex interactional/organisational factors are all-important when considering how abuse is perpetuated within the healthcare workplace. Although some organisational factors may be difficult to change, we recommend that educational initiatives are a key starting point to tackle healthcare workplace abuse.

Optimising faecal occult blood screening:retrospective analysis of NHS Bowel Cancer Screening data to improve the screening algorithm.

BACKGROUND: Colorectal neoplasia causes bleeding, enabling detection using Faecal Occult Blood tests (FOBt). The National Health Service (NHS) Bowel Cancer Screening Programme (BCSP) guaiac-based FOBt (gFOBt) kits contain six sample windows (or 'spots') and each kit returns either a positive, unclear or negative result. Test kits with five or six positive windows are termed 'abnormal' and the subject is referred for further investigation, usually colonoscopy. If 1-4 windows are positive, the result is initially 'unclear' and up to two further kits are submitted, further positivity leads to colonoscopy ('weak positive'). If no further blood is detected, the test is deemed 'normal' and subjects are tested again in 2 years' time. We studied the association between spot positivity % (SP%) and neoplasia. METHODS: Subjects in the Southern Hub completing the first of two consecutive episodes between April 2009 and March 2011 were studied. Each episode included up to three kits and a maximum of 18 windows (spots). For each positivity combination, the percentage of positive spots out of the total number of spots completed by an individual in a single-screening episode was derived and named 'SP%'. Fifty-five combinations of SP can occur if the position of positive/negative spots on the same test card is ignored.The proportion of individuals for whom neoplasia was identified in Episode 2 was derived for each of the 55 spot combinations. In addition, the Episode 1 spot pattern was analysed for subjects with cancer detected in Episode 2. RESULTS: During Episode 2, 284,261 subjects completed gFOBT screening and colonoscopies were performed on 3891 (1.4%) subjects. At colonoscopy, cancer was detected in 7.4% (n=286) and a further 39.8% (n=1550) had adenomas. Cancer was detected in 21.3% of subjects with an abnormal first kit (five or six positive spots) and in 5.9% of those with a weak positive test result.The proportion of cancers detected was positively correlated with SP%, with an R(2) correlation (linear) of 0.89. As the SP% increased from 11 to 100%, so the colorectal cancer (CRC) detection rate increased from 4 to 25%. At the lower SP%s, from 11to 25%, the CRC risk was relatively static at ~4%. Above an SP% of 25%, every 10-percentage points increase in the SP%, was associated with an increase in cancer detection of 2.5%. CONCLUSIONS: This study demonstrated a strong correlation between SP% and cancer detection within the NHS BCSP. At the population level, subjects' cancer risk ranged from 4 to 25% and correlated with the gFOBt spot pattern.Some subjects with an SP% of 11% proceed to colonoscopy, whereas others with an SP% of 22% do not. Colonoscopy on patients with four positive spots in kit 1 (SP% 22%) would, we estimate, detect cancer in ~4% of cases and increase overall colonoscopy volume by 6%. This study also demonstrated how screening programme data could be used to guide its ongoing implementation and inform other programmes.

Screen-detected colorectal cancers are associated with an improved outcome compared with stage-matched interval cancers.

BACKGROUND: Colorectal cancers (CRCs) detected through the NHS Bowel Cancer Screening Programme (BCSP) have been shown to have a more favourable outcome compared to non-screen-detected cancers. The aim was to identify whether this was solely due to the earlier stage shift of these cancers, or whether other factors were involved. METHODS: A combination of a regional CRC registry (Northern Colorectal Cancer Audit Group) and the BCSP database were used to identify screen-detected and interval cancers (diagnosed after a negative faecal occult blood test, before the next screening round), diagnosed between April 2007 and March 2010, within the North East of England. For each Dukes' stage, patient demographics, tumour characteristics, and survival rates were compared between these two groups. RESULTS: Overall, 322 screen-detected cancers were compared against 192 interval cancers. Screen-detected Dukes' C and D CRCs had a superior survival rate compared with interval cancers (P=0.014 and P=0.04, respectively). Cox proportional hazards regression showed that Dukes' stage, tumour location, and diagnostic group (HR 0.45, 95% CI 0.29-0.69, P<0.001 for screen-detected CRCs) were all found to have a significant impact on the survival of patients. CONCLUSIONS: The improved survival of screen-detected over interval cancers for stages C and D suggest that there may be a biological difference in the cancers in each group. Although lead-time bias may have a role, this may be related to a tumour's propensity to bleed and therefore may reflect detection through current screening tests.

The relationship between magical thinking, inferential confusion and obsessive-compulsive symptoms.

Inferential confusion is an under-researched faulty reasoning process in obsessive-compulsive disorder (OCD). Based on an overreliance on imagined possibilities, it shares similarities with the extensively researched construct of thought-action fusion (TAF). While TAF has been proposed as a specific subset of the broader construct of magical thinking, the relationship between inferential confusion and magical thinking is unexplored. The present study investigated this relationship, and hypothesised that magical thinking would partially mediate the relationship between inferential confusion and obsessive-compulsive symptoms. A non-clinical sample of 201 participants (M = 34.94, SD = 15.88) were recruited via convenience sampling. Regression analyses found the hypothesised mediating relationship was supported, as magical thinking did partially mediate the relationship between inferential confusion and OC symptoms. Interestingly, inferential confusion had the stronger relationship with OC symptoms in comparison to the other predictor variables. Results suggest that inferential confusion can both directly and indirectly (via magical thinking) impact on OC symptoms. Future studies with clinical samples should further investigate these constructs to determine whether similar patterns emerge, as this may eventually inform which cognitive errors to target in treatment of OCD.

From pelvic radiation to social isolation: a qualitative study of survivors' experiences of chronic bowel symptoms after pelvic radiotherapy.

PURPOSE: We explored survivors' experiences of chronic bowel symptoms following pelvic radiotherapy, strategies employed in living with these symptoms, effects on daily activities, and roles at home and in the workplace. METHODS: Semi-structured interviews were conducted with 28 individuals (10 gynaecological, 14 prostate, four anal/rectal cancer survivors) who had completed pelvic radiotherapy at least six months prior to data collection and who had experience of bowel symptoms during this post-treatment period. Reflexive thematic analysis was undertaken. RESULTS: We propose four themes describing a process leading from experience of symptoms to withdrawal from activities and roles. These are (1) losing control (the experience of unintended anal leakage or discharge); (2) experiencing embarrassment and fear (the experience of embarrassment or fear of embarrassment as a result of discharge becoming public); (3) managing and reacting (acting to reduce the likelihood of discharge or to prevent this becoming public); and (4) restriction and withdrawal (avoiding specific activities or situations so as to reduce or remove the risk of embarrassment). Returning to the workplace presented additional challenges across these themes. CONCLUSIONS: Impacts of chronic bowel symptoms can be severe. Survivors employ a variety of methods and strategies in living with their symptoms. Some of these support continued role fulfilment but some constitute a withdrawal from pre-treatment roles. Current healthcare provision and statutory protections fail to fully meet needs following pelvic radiotherapy. IMPLICATIONS FOR CANCER SURVIVORS: There is a need to develop and implement evidence-based services and supported self-management programmes for survivors experiencing chronic bowel problems post-radiotherapy.

Experience on postmortem minimally invasive tissue sampling to ascertain the cause of death determination in South African children: A case for implementing as standard of care.

Determining the death burden for prioritising public health interventions necessitates detailed data on the causal pathways to death. Postmortem minimally invasive tissue sampling (MITS), incorporating histology, molecular and microbial culture diagnostics, enhances cause-of-death attribution, particularly for infectious deaths. MITS proves a valid alternative to full diagnostic autopsies, especially in low- and middle-income countries. In Soweto, South Africa (SA), the Child Health and Mortality Prevention Surveillance (CHAMPS) programme has delineated over 1 000 child and stillbirth deaths since 2017. This SA CHAMPS site supports advocating for the use of postmortem MITS as routine practice, for more granular insights into under-5 mortality causes. This knowledge is crucial for SA's pursuit of Sustainable Development Goal 3.2, targeting reduced neonatal and under-5 mortality rates. This commentary explores the public health advantages and ethicolegal considerations surrounding implementing MITS as standard of care for stillbirths, neonatal and paediatric deaths in SA. Furthermore, based on the data from CHAMPS, we present three pragmatic algorithmic approaches to the wide array of testing options for cost-effectiveness and scalability of postmortem MITS in South African state facilities.

Maintenance durvalumab after first-line chemotherapy in patients with HER2-negative advanced oesophago-gastric adenocarcinoma: results from the randomised PLATFORM study.

BACKGROUND: PLAnning Treatment For Oesophago-gastric Cancer: a Randomised Maintenance Therapy Trial (PLATFORM) is an adaptive phase II study assessing the role of maintenance therapies in advanced oesophago-gastric (OG) adenocarcinoma. We evaluated the role of the anti-programmed death-ligand 1 (PD-L1) inhibitor durvalumab in these patients. PATIENTS AND METHODS: Patients with human epidermal growth factor receptor 2-negative locally advanced or metastatic OG adenocarcinoma with disease control or response to 18 weeks of platinum-based first-line chemotherapy were randomised to active surveillance or maintenance durvalumab. The primary endpoint was progression-free survival (PFS). Safety was assessed in all patients who had commenced surveillance visits or received at least one dose of durvalumab. Exploratory survival analyses according to PD-L1 Combined Positive Score (CPS) and immune (biomarker-positive) or angiogenesis dominant (biomarker-negative) tumour microenvironment (TME) phenotypes were conducted. RESULTS: Between March 2015 and April 2020, 205 patients were randomised to surveillance (n = 100) and durvalumab (n = 105). No significant differences were seen in PFS [hazard ratio (HR) 0.84, P = 0.13] and overall survival (OS; HR 0.98, P = 0.45) between surveillance and durvalumab. Five patients randomised to durvalumab demonstrated incremental radiological responses compared with none with surveillance. Treatment-related adverse events occurred in 77 (76.2%) durvalumab-assigned patients. A favourable effect in OS with durvalumab over surveillance in CPS ≥5 and immune biomarker-positive patients was observed compared with CPS <5 and biomarker-negative subgroups, respectively: CPS ≥5 versus <5: HR 0.63, 95% confidence interval (CI) 0.32-1.22 versus HR 0.93, 95% CI 0.44-1.96; biomarker-positive versus negative: HR 0.60, 95% CI 0.29-1.23 versus HR 0.84, 95% CI 0.42-1.65. CONCLUSION: Maintenance durvalumab does not improve PFS in patients with OG adenocarcinoma who respond to first-line chemotherapy but induced incremental radiological responses in a subset of patients. TME characterisation could refine patient selection for anti-PD-L1 therapy above PD-L1 CPS alone.

A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma.

BACKGROUND: PEP02 is a novel highly stable liposomal nanocarrier formulation of irinotecan. This randomized phase II study evaluated the efficacy and safety of single agent PEP02 compared with irinotecan or docetaxel in the second-line treatment of advanced oesophago-gastric (OG) cancer. PATIENTS AND METHODS: Patients with locally advanced/metastatic disease who had failed one prior chemotherapy regimen were randomly assigned to PEP02 120 mg/m(2), irinotecan 300 mg/m(2) or docetaxel (Taxotere) 75 mg/m(2) every 3 weeks. The primary end point was objective response rate (ORR). Simon's two-stage design was used and the ORR of interest was 20% (α = 0.05, type II error ß = 0.10, null hypothesis of ORR was 5%). RESULTS: Forty-four patients per arm received treatment, and 124 were assessable for response. The ORR statistical threshold for the first stage was reached in all arms. In the intent-to-treat (ITT) population, ORRs were 13.6% (6/44), 6.8% (3/44) and 15.9% (7/44) in the PEP02, irinotecan and docetaxel arms, respectively. The median progression-free survival (PFS) and overall survival were similar between the trial arms. Commonest grade 3-4 adverse event reported was diarrhoea in the PEP02 and irinotecan groups (27.3% versus 18.2%). CONCLUSION: The ORR associated with PEP02 was comparable with docetaxel and numerically greater than that of irinotecan. PEP02 warrants further evaluation in the advanced gastric cancer setting.

Management of complex colonic polyps in the English Bowel Cancer Screening Programme.

BACKGROUND: Large sessile or flat colonic polyps, defined as polyps at least 20 mm in size, are difficult to treat endoscopically and may harbour malignancy. The aim of this study was to describe their current management to provide insight into optimal management. METHODS: This retrospective observational study identified patients with large sessile or flat polyps detected in the English Bowel Cancer Screening Programme between 2006 and 2009. Initial therapeutic modality (surgical or endoscopic), subsequent management and outcomes were recorded. The main outcome measures analysed were: presence of malignancy, need for surgical treatment, complications, and residual or recurrent polyp at 12 months. RESULTS: In total, 557 large sessile or flat polyps with benign appearance or initial histology were identified in 557 patients. Some 436 (78.3 per cent) were initially managed endoscopically and 121 (21.7 per cent) were managed surgically from the outset. Seventy of those initially treated endoscopically subsequently required surgery owing to the presence of malignancy (19) or not being suitable for further endoscopic management (51). Residual or recurrent polyp was present at 12 months in 26 (6.0 per cent) of 436 patients managed endoscopically. There was wide variation between centres in the use of surgery as a primary therapy, ranging from 7 to 36 per cent. Endoscopic complications included bleeding in 13 patients (3.0 per cent) and perforation in two (0.5 per cent). CONCLUSION: Management of large sessile or flat colonic polyps is safe and effective in the English Bowel Cancer Screening Programme. Wide variation in the use of surgery suggests a need for standardized management algorithms. Presented to a meeting of the British Society of Gastroenterology, Birmingham, U.K., March 2011.

Longer mean colonoscopy withdrawal time is associated with increased adenoma detection: evidence from the Bowel Cancer Screening Programme in England.

BACKGROUND AND STUDY AIMS: Increasing colonoscopy withdrawal time (CWT) is thought to be associated with increasing adenoma detection rate (ADR). Current English guidelines recommend a minimum CWT of 6 minutes. It is known that in the Bowel Cancer Screening Programme (BCSP) in England there is wide variation in CWT. The aim of this observational study was to examine the relationship between CWT and ADR. PATIENTS AND METHODS: The study examined data from 31 088 colonoscopies by 147 screening program colonoscopists. Colonoscopists were grouped in four levels of mean CWT ( < 7, 7 - 8.9, 9 - 10.9, and ≥ 11 minutes). Univariable and multivariable analysis (binary logistic and negative binomial regression) were used to explore the relationship between CWT, ADR, mean number of adenomas and number of right-sided and advanced adenomas. RESULTS: In colonoscopists with a mean CWT < 7 minutes, the mean ADR was 42.5 % compared with 47.1 % in the ≥ 11-minute group (P < 0.001). The mean number of adenomas detected per procedure increased from 0.77 to 0.94, respectively (P < 0.001). The increase in adenoma detection was mainly of subcentimeter or proximal adenomas; there was no increase in the detection of advanced adenomas. Regression models showed an increase in ADR from 43 % to 46.5 % for mean CWT times ranging from 6 to 10 minutes. CONCLUSIONS: This study demonstrates that longer mean withdrawal times are associated with increasing adenoma detection, mainly of small or right-sided adenomas. However, beyond 10 minutes the increase in ADR is minimal. Mean withdrawal times longer than 6 minutes are not associated with increased detection of advanced adenomas. Withdrawal time remains an important quality metric of colonoscopy.

Outcome of 12-month surveillance colonoscopy in high-risk patients in the National Health Service Bowel Cancer Screening Programme.

AIM: Current British guidelines recommend surveillance colonoscopy at 12 months for individuals found to have five or more adenomas, or three or more adenomas of which at least one is ≥ 1 cm in size. This study describes the yield of surveillance colonoscopy in this group and explores patient and clinical factors that may be associated with the presence of advanced adenomas or cancer at surveillance. METHOD: Data were retrieved from the national database of the National Health Service Bowel Cancer Screening Programme. The detection of advanced colonic neoplasia (ACN, cancer or advanced adenoma) was used as the main outcome variable. Multivariable analysis was used to analyse relationships between patient factors (age, gender, body mass index, smoking and alcohol use) and clinical findings (number, size and nature of adenomas detected during index colonoscopy) with the outcome variable. RESULTS: One-thousand, seven-hundred and sixty individuals were included in the study. The yield of ACN at 12-month surveillance was 6.6% (116/1760), of which 14/1760 (0.8%) had colorectal cancer. Nine (64.3%) of these 14 cancers were Dukes A at diagnosis. The presence of a villous adenoma or a right-sided adenoma at screening colonoscopy was associated with ORs of 1.98 (95% CI: 1.11-3.53, P = 0.012) and 1.76 (95% CI: 1.13-2.74, P = 0.020), respectively, for detection of ACN at surveillance. CONCLUSION: Twelve-month surveillance colonoscopy is necessary in this group of patients. The presence of villous or proximal lesions at baseline is associated with increased risk of ACN at surveillance. Site and histological type of baseline lesions may be relevant for determining the surveillance interval.

Systematic variation in gene expression patterns in human cancer cell lines.

We used cDNA microarrays to explore the variation in expression of approximately 8,000 unique genes among the 60 cell lines used in the National Cancer Institute's screen for anti-cancer drugs. Classification of the cell lines based solely on the observed patterns of gene expression revealed a correspondence to the ostensible origins of the tumours from which the cell lines were derived. The consistent relationship between the gene expression patterns and the tissue of origin allowed us to recognize outliers whose previous classification appeared incorrect. Specific features of the gene expression patterns appeared to be related to physiological properties of the cell lines, such as their doubling time in culture, drug metabolism or the interferon response. Comparison of gene expression patterns in the cell lines to those observed in normal breast tissue or in breast tumour specimens revealed features of the expression patterns in the tumours that had recognizable counterparts in specific cell lines, reflecting the tumour, stromal and inflammatory components of the tumour tissue. These results provided a novel molecular characterization of this important group of human cell lines and their relationships to tumours in vivo.