Research protocol for a diagnostic study of non-invasive exhaled breath analysis for the prediction of oesophago-gastric cancer

INTRODUCTION: Despite improvements in a range of chemo, radio and surgical therapies, the overall survival at 5 years from oesophago-gastric cancer remains poor and ranges from 10% to 30%. Early diagnosis is a key strategy to improve survival but early disease stage has non-specific symptoms that are very common while the warning clinical picture often indicates advanced disease. The aim of this research is to validate a breath test to predict oesophago-gastric cancer therefore allowing earlier diagnosis and introduction of treatment. METHODS AND ANALYSIS: The study will include 325 patients and be conducted across four major oesophago-gastric cancer centres in London, UK. This research will utilise selected ion flow-tube mass spectrometry (SIFT-MS) exhaled breath analysis, for comparison of predicted cancer risk based on the previously developed volatile organic compound exhaled breath model, with endoscopic findings and histology biopsies. This will determine the overall diagnostic accuracy for non-invasive breath testing for the diagnosis of oesophago-gastric cancer. ETHICS AND DISSEMINATION: Approval was gained from NRES Committee London, on 16 July 2014 (REC reference 14/LO/1136) for the completion of this study. Different methods of dissemination will be employed including international clinical and patient group presentations, and publication of research outputs in a high-impact clinical journal. This is to ensure that the findings from this research will reach patients, primary care practitioners, scientists, hospital specialists in gastroenterology, oncology and surgery, health policymakers and commissioners as well as NHS regulatory bodies. TRIALS REGISTRATION NUMBER: UKCRN18063; Pre-results

Surgery during holiday periods and prognosis in oesophageal cancer: a population-based nationwide Swedish cohort study

OBJECTIVE: Previous studies indicate an increased short-term and long-term mortality from major cancer surgery performed towards the end of the working week or during the weekend. We hypothesised that the prognosis after major cancer surgery is also negatively influenced by surgery conducted during holiday periods. SETTING: Population-based nationwide Swedish cohort study. PARTICIPANTS: Patients undergoing oesophagectomy for oesophageal cancer between 1987 and 2010. Among 1820 included patients, 206 (11.3%) and 373 (20.5%) patients were operated on during narrow and wide holiday periods, respectively. INTERVENTIONS: Narrow (7 weeks) and wide (14 weeks) Swedish holiday periods. PRIMARY AND SECONDARY OUTCOME MEASURES: 90-day all-cause, 5-year all-cause and 5-year disease-specific mortality. RESULTS: Narrow holiday period did not increase all-cause 90-day (HR=0.84, 95% CI 0.53 to 1.33), all-cause 5-year (HR=1.01, 95% CI 0.85 to 1.21) or disease-specific 5-year mortality (HR=1.04, 95% CI 0.87 to 1.26). Similarly, wide holiday period did not increase the risk of 90-day (HR=0.79, 95% CI 0.55 to 1.13), all-cause 5-year (HR=0.96, 95% CI 0.84 to 1.1) or disease-specific 5-year mortality (HR=1.03, 95% CI 0.89 to 1.19). CONCLUSIONS: No measurable effects of holiday periods on short-term or longer term mortality following surgery for oesophageal cancer were observed in this population-based study, indicating that an adequate surgical experience was maintained during holiday periods

Biomarkers of acute appendicitis: systematic review and cost–benefit trade-off analysis

BACKGROUND: Acute appendicitis is the most common surgical emergency and can represent a challenging diagnosis, with a negative appendectomy rate as high as 20 %. This review aimed to evaluate the clinical utility of individual biomarkers in the diagnosis of appendicitis and appraise the quality of these studies. METHODS: A systematic review of the literature between January 2000 and September 2015 using of PubMed, OvidMedline, EMBASE and Google Scholar was conducted. Studies in which the diagnostic accuracy, statistical heterogeneity and predictive ability for severity of several biomarkers could be elicited were included. Information regarding costs and process times was retrieved from the regional laboratory. European surgeons blinded to these reviews were independently asked to rank which characteristics of biomarkers were most important in acute appendicitis to inform a cost-benefit trade-off. Sensitivity testing and the QUADAS-2 tool were used to assess the robustness of the analysis and study quality, respectively. RESULTS: Sixty-two studies met the inclusion criteria and were assessed. Traditional biomarkers (such as white cell count) were found to have a moderate diagnostic accuracy (0.75) but lower costs in the diagnosis of acute appendicitis. Conversely, novel markers (pro-calcitonin, IL 6 and urinary 5-HIAA) were found to have high process-related costs including analytical times, but improved diagnostic accuracy. QUADAS-2 analysis revealed significant potential biases in the literature. CONCLUSION: When assessing biomarkers, an appreciation of the trade-offs between the costs and benefits of individual biomarkers is needed. Further studies should seek to investigate new biomarkers and address concerns over bias, in order to improve the diagnosis of acute appendicitis

The Role of Heterogeneous Parameters for the Detection of Selection in Insurance Contracts

This study re-examines standard econometric approaches for detecting adverse and advantageous selection in insurance contracts based on variables that are not used for calculating the insurance premium. We formally demonstrate that existing strategies for detecting selection based on such ‘unused characteristics’ can lead to incorrect conclusions if the estimated coefficients of interest are driven by different parts of the population. We show that this issue can empirically be accounted for by allowing for heterogeneous parameters. We compare existing approaches by using simulated data with different selection regimes and test for parameter heterogeneity within the data. We further provide empirical evidence about selection into the market for private health insurance in England. Both our simulations, and the findings using real data, suggest that parameter heterogeneity is a relevant issue that can confound the interpretation of standard ‘unused characteristics’ approaches. Our findings are important for analysing the efficiency of insurance markets. They are of interest to both the insurance industry and policymakers, and should be accounted for when selection based on specific characteristics needs to be detected or the effects of structural changes of insurance policies/markets are to be predicted

Applied investigation of person-specific and context-specific factors on postoperative recovery and clinical outcomes of patients undergoing gastrointestinal cancer surgery: multicentre European study

INTRODUCTION: Cancer treatments have greatly advanced over the past two decades causing survival improvements and reduced complications from cancer surgery. However, the cancer diagnosis and the effects of treatment modalities pose a major risk to patients' psychological well-being. Given current interest and emerging evidence about the importance of psychological and social factors on cancer survival and coping with cancer treatments, this study will build and expand research in order to identify key modifiable psychosocial variables that contribute to better physical and mental health following gastrointestinal cancer (GIC) surgery. OBJECTIVES: To elucidate the incidence of postoperative psychiatric morbidity within 6 months following GIC surgery. To identify key measurable modifiable preoperative psychological factors that can significantly affect postoperative psychiatric morbidity in patients undergoing surgery for GIC. To clarify the changes seen in a patient's psychological well-being during their treatment pathway for GIC. METHODS AND ANALYSIS: This multicentre study has an observational longitudinal study design. In total, 1000 patients will be screened with a multicomponent psychological questionnaire at four different time points: at diagnosis, preoperatively, 1 and 6 months after surgery. Data from this questionnaire will be linked to postoperative complications including psychiatric morbidity, length of hospital stay and recovery to normal activity. ETHICS AND DISSEMINATION: NHS Health Research Authority approval was gained on (REC reference 15.LO/1847) for the completion of this study. Multiple platforms will be used for the dissemination of the research data, including international clinical and patient group presentations and publication of research outputs in a high impact clinical journal

Improving surgical therapy for oesophageal cancer

Despite advances in multimodality treatment, surgery remains the mainstay of curative treatment for oesophageal cancer. However short- and long-term mortality from oesophagectomy for oesophageal cancer still shows large variations nationally and internationally. This thesis addresses three themes concerning oesophageal cancer surgery. The first theme focuses on technical challenges, learning in surgery and the influence of surgeon age on outcomes from oesophagectomy. Study I utilised a large French multi-centre database (FREGAT), and showed in contrast to previous smaller single-centre studies, salvage oesophagectomy after definitive chemoradiotherapy can offer acceptable short- and long- term outcomes in selected patients at experienced oesophageal cancer centres. Study II used a national Swedish dataset (SESS) and demonstrated that the period during which surgeons gain proficiency in performing oesophagectomy for cancer is associated with substantial adverse effects upon short- and long-term mortality at a national level. The length of the proficiency gain period was longer for long-term mortality than for short-term mortality, implying a change in surgeon focus during the initial stages of their independent practice. Study III also used the SESS and was able to show the optimal surgeon age in performing oesophagectomy in Sweden is between 51 and 56 years. Outside of this age period, increases in short- and long-term mortality are noted, as surgeons are still gaining experience or maybe experiencing decline in their technical abilities. The second theme, sought to evaluate the effect of hospital factors, which may affect outcome from oesophagectomy for cancer. Study IV used SESS once more, and showed surgery performed in university hospitals has no improvements in long-term mortality from oesophagectomy after adjustment for surgeon volume and other confounders. The third theme of this thesis considered the effect of complications during treatment for oesophageal cancer upon long-term prognosis. Study V used FREGAT and demonstrated severe oesophageal anastomotic leak following oesophagectomy for cancer, adversely impacts cancer prognosis with a decrease in overall and disease-free survival and an increasing in overall, loco-regional and mixed cancer recurrence. In conclusion, the studies conducted within this thesis have shown the safety of new therapeutic surgical strategies for oesophageal cancer, the importance of surgeon proficiency gain and surgeon age in prognosis, the lack of significance of university hospital status, and the adverse long-term prognostic effects of severe oesophageal anastomotic leak

Spot urinary 5-hydroxyindoleacetic acid is not an ideal diagnostic test for acute appendicitis

Background and purpose of the studyThere is growing evidence to suggest the use of urinary 5-hydroxyindoleacetic acid (5-HIAA) test to help with the diagnosis of appendicitis. The aim of our study was to establish whether urinary 5-HIAA could be used as an effective diagnostic test for acute appendicitis.Design and methodsA prospective double-blinded study was carried out from December 2014 to October 2015. Patients admitted to the emergency surgical ward of a teaching hospital with suspected appendicitis were included in the study. The diagnostic accuracy of the test was measured by receiver operating characteristic curve.ResultsNinety-seven patients were divided into 2 groups: acute appendicitis (n = 38) and other diagnosis (n = 59). The median value of urinary 5-HIAA was 24.19 μmol/L (range, 5.39-138.27) for acute appendicitis vs 18.87 μmol/L (range, 2.27-120.59) for other diagnosis group (P = .038). The sensitivity and specificity of urinary 5-HIAA at a cutoff value of 19 μmol/L were 71% and 50%, respectively. Receiver operating characteristic analysis showed that the area under curve was 0.64 (confidence interval [CI], 0.513-0.737) for urinary 5-HIAA, which was lower than white blood cell count (0.69; CI, 0.574-0.797), neutrophil count (0.68; CI, 0.565-0.792), and C-reactive protein (0.76; CI, 0.657-0.857). There was no significant difference in the median values of 5-HIAA between different grades of severity of appendicitis (P = .704).ConclusionUrinary 5-HIAA is not an ideal test for the diagnosis of acute appendicitis

Sisters to Scheherazade: Revisioned Histories of Gender and Nation in Postcolonial African and Asian Women's Literature

PhDTraversing geographical boundaries and cultural locations, and using a comparative, crosscultural framework, this thesis examines and critiques a selected range of women's writings from postcolonial Africa and Asia. It foregrounds the works of Assia Djebar, Mariama Ba, Ama Ata Aidoo, Nayantara Sahgal and Attia Hosain and outlines the processes through which women writers decentre imperialist, patriarchal underpinnings of the grand recit, defy conventions of autobiographical practice, make sense of a feminized past and revision a different collective personal history that has emancipatory potential for women and other oppressed groups. Referring to Eurocentric "male-stream" histories that have systematically thrust women to the margins, the study illustrates through a variety of literary texts and genres the complex ways in which past histories have obliterated women's presence and voiceconsciousness. While appraising diverse textual strategies of narratives, it discusses the "fictional" nature of historical work and the underlying ideologies framing supposedly "truthful" archival records; the ambivalent role of the historian; the gaps and fissures in historical memory; and the significance of history as a palimpsest. By excavating subsumed histories and "spectres" of the past, the study assesses the way specific texts reconstruct totalizing masculinist chronicles and counterpoise them with alternative feminine inscriptions that are multi-layered and polyphonic, and sometimes also fragmented, "silent" and inconclusive. Additionally, the thesis demonstrates how the process of overwriting the palimpsest has situated women in pivotal positions to articulate issues relevant to a dialogue between gender and nation/atism. The strategic role women have undertaken in decolonization processes worldwide, the ambivalent attitude of male nationalists to women's concerns after independence, and the multiple dilemmas confronting women in a globalized neoimperial world scenario are central to this discussion. Here, the thesis also probes the implications of veiling for Muslim women of contemporary times, sex-segregation based on an antiquated ideology of purdah, women's (limited) access to public space, and the question of agency and women's voice-consciousness. The study highlights current global conditions (such as modern migrations and economic transnationalism) and multiple categories of race, class, gender and ethnicity that intersect in complex ways to represent the Otherized identities of women