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

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

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

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

A national survey assessing public readiness for digital health strategies against COVID-19 within the United Kingdom

There is concern that digital public health initiatives used in the management of COVID-19 may marginalise certain population groups. There is an overlap between the demographics of groups at risk of digital exclusion (older, lower social grade, low educational attainment and ethnic minorities) and those who are vulnerable to poorer health outcomes from SARS-CoV-2. In this national survey study (n=2040), we assessed how the UK population; particularly these overlapping groups, reported their preparedness for digital health strategies. We report, with respect to using digital information to make health decisions, that those over 60 are less comfortable (net comfort: 57%) than those between 18-39 (net comfort: 78%) and lower social grades are less comfortable (net comfort: 63%) than higher social grades (net comfort: 75%). With respect to a preference for digital over non-digital sources in seeking COVID-19 health information, those over 60 (net preference: 21%) are less inclined than those between 18-39 (net preference: 60%) and those of low educational attainment (net preference: 30%) are less inclined than those of high educational attainment (net preference: 52%). Lastly, with respect to distinguishing reliable digital COVID-19 information, lower social grades (net confidence: 55%) are less confident than higher social grades (net confidence: 68%) and those of low educational attainment (net confidence: 51%) are less confident than those of high educational attainment (net confidence: 71%). All reported differences are statistically significant (p<0.01) following multivariate regression modelling. This study suggests that digital public health approaches to COVID-19 have the potential to marginalise groups who are concurrently at risk of digital exclusion and poor health outcomes from SARS-CoV-2

Prognostic significance of peritoneal lavage cytology in staging gastric cancer: systematic review and meta-analysis

Background Peritoneal cytology has been used as a part of the cancer staging of gastric cancer patients. The primary aim of this systematic review was to evaluate the value of peritoneal cytology as part of the staging of gastric cancer and survival prediction. The second aim was to establish if positive cytology may be modified by neoadjuvant therapy, to improve prognosis. Methods An electronic literature search was performed using Embase, Medline, Web of Science, and Cochrane library databases up to January 2016. The logarithm of the hazard ratio (HR) with 95% confidence intervals (CI) was used as the primary summary statistic. Comparative studies were used, and the outcome measure was survival in three groups: (1) positive versus negative cytology at staging laparoscopy immediately preceding surgery; (2) effect of neoadjuvant therapy on cytology and survival; and (3) positive cytology in the absence of macroscopic peritoneal disease was compared with obvious macroscopic peritoneal disease. Results Pooled analysis demonstrated that positive cytology was associated with significantly reduced overall survival (HR, 3.46; 95% CI, 2.77–4.31; P < 0.0001). Interestingly, negative cytology following neoadjuvant chemotherapy was associated with significantly improved overall survival (HR, 0.42; 95% CI, 0.31–0.57; P < 0.0001). The absence of macroscopic peritoneal disease with positive cytology was associated with significantly improved overall survival (HR, 0.64; 95% CI, 0.56–0.73; P < 0.0001). Conclusion This study suggests that patients with initial positive cytology may have a good prognosis following neoadjuvant treatment if the cytology results change to negative after treatment

The psychological impact of symptoms related to esophagogastric cancer resection presenting in primary care: A national linked database study

Background The objective was to evaluate incidence, risk factors and impact of postoperative symptoms following esophagogastric cancer resection in primary care. Methods Patients undergoing esophagogastrectomy for cancer from 1998 to 2010 with linked records in Clinical Practice Research Datalink, Hospital Episodes Statistics and Office of National Statistics databases were studied. The recording of codes for reflux, dysphagia, dyspepsia, nausea, vomiting, dumping, diarrhea, steatorrhea, appetite loss, weight loss, pain and fatigue were identified up to 12 months postoperatively. Psychiatric morbidity was also examined and its risk evaluated by logistic regression analysis. Results Overall, 58.6% (1029/1755) of patients were alive 2 years after surgery. Of these, 41.1% had recorded postoperative symptoms. Reflux, dysphagia, dyspepsia and pain were more frequent following esophagectomy compared with gastrectomy (p < 0.05). Complications (OR = 1.40 95%CI 1.00–1.95) and surgical procedure predicted postoperative symptoms (p < 0.05). When compared with partial gastrectomy, esophagectomy (OR = 2.03 95%CI 1.26–3.27), total gastrectomy (OR = 2.44 95%CI 1.57–3.79) and esophagogastrectomy (OR = 2.66 95%CI 1.85–2.86) were associated with postoperative symptoms (p < 0.05). The majority of patients with postoperative psychiatric morbidity had depression or anxiety (98%). Predictors of postoperative depression/anxiety included younger age (OR = 0.97 95%CI 0.96–0.99), complications (OR = 2.40 95%CI 1.51–3.83), psychiatric history (OR = 6.73 95%CI 4.25–10.64) and postoperative symptoms (OR = 1.78 95%CI 1.17–2.71). Conclusions Over 40% of patients had symptoms related to esophagogastric cancer resection recorded in primary care, and were associated with an increase in postoperative depression and anxiety

Cardiorespiratory comorbidity and postoperative complications following esophagectomy: a European multicenter cohort study

BACKGROUND: The impact of cardiorespiratory comorbidity on operative outcomes after esophagectomy remains controversial. This study investigated the effect of cardiorespiratory comorbidity on postoperative complications for patients treated for esophageal or gastroesophageal junction cancer. PATIENTS AND METHODS: A European multicenter cohort study from five high-volume esophageal cancer centers including patients treated between 2010 and 2017 was conducted. The effect of cardiorespiratory comorbidity and respiratory function upon postoperative outcomes was assessed. RESULTS: In total 1590 patients from five centers were included; 274 (17.2%) had respiratory comorbidity, and 468 (29.4%) had cardiac comorbidity. Respiratory comorbidity was associated with increased risk of overall postoperative complications, anastomotic leak, pulmonary complications, pneumonia, increased Clavien-Dindo score, and critical care and hospital length of stay. After neoadjuvant chemoradiotherapy, respiratory comorbidity was associated with increased risk of anastomotic leak [odds ratio (OR) 1.83, 95% confidence interval (CI) 1.11-3.04], pneumonia (OR 1.65, 95% CI 1.10-2.47), and any pulmonary complication (OR 1.52, 95% CI 1.04-2.22), an effect which was not observed following neoadjuvant chemotherapy or surgery alone. Cardiac comorbidity was associated with increased risk of cardiovascular and pulmonary complications, respiratory failure, and Clavien-Dindo score ≥ IIIa. Among all patients, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio > 70% was associated with reduced risk of overall postoperative complications, cardiovascular complications, atrial fibrillation, pulmonary complications, and pneumonia. CONCLUSIONS: The results of this study suggest that cardiorespiratory comorbidity and impaired pulmonary function are associated with increased risk of postoperative complications after esophagectomy performed in high-volume European centers. Given the observed interaction with neoadjuvant approach, these data indicate a potentially modifiable index of perioperative risk