De Novo Lipogenesis Alters the Phospholipidome of Esophageal Adenocarcinoma.

The incidence of esophageal adenocarcinoma is rising, survival remains poor, and new tools to improve early diagnosis and precise treatment are needed. Cancer phospholipidomes quantified with mass spectrometry imaging (MSI) can support objective diagnosis in minutes using a routine frozen tissue section. However, whether MSI can objectively identify primary esophageal adenocarcinoma is currently unknown and represents a significant challenge, as this microenvironment is complex with phenotypically similar tissue-types. Here, we used desorption electrospray ionization-MSI (DESI-MSI) and bespoke chemometrics to assess the phospholipidomes of esophageal adenocarcinoma and relevant control tissues. Multivariate models derived from phospholipid profiles of 117 patients were highly discriminant for esophageal adenocarcinoma both in discovery (AUC = 0.97) and validation cohorts (AUC = 1). Among many other changes, esophageal adenocarcinoma samples were markedly enriched for polyunsaturated phosphatidylglycerols with longer acyl chains, with stepwise enrichment in premalignant tissues. Expression of fatty acid and glycerophospholipid synthesis genes was significantly upregulated, and characteristics of fatty acid acyls matched glycerophospholipid acyls. Mechanistically, silencing the carbon switch ACLY in esophageal adenocarcinoma cells shortened glycerophospholipid chains, linking de novo lipogenesis to the phospholipidome. Thus, DESI-MSI can objectively identify invasive esophageal adenocarcinoma from a number of premalignant tissues and unveils mechanisms of phospholipidomic reprogramming. SIGNIFICANCE: These results call for accelerated diagnosis studies using DESI-MSI in the upper gastrointestinal endoscopy suite, as well as functional studies to determine how polyunsaturated phosphatidylglycerols contribute to esophageal carcinogenesis.

Prone or Left for Colonoscopy? A Randomized Controlled Trial of Prone Versus Left-sided Starting Position for Colonoscopy.

BACKGROUND AND AIMS: Data have emerged supporting the right-lateral starting position in reducing time to cecum and improving patient comfort for minimally sedated colonoscopy. We aimed to test whether prone starting position results in similar advantages in procedure time and patient tolerability in comparison to traditional left-sided starting position. MATERIALS AND METHODS: We conducted a randomized controlled trial in which patients were randomized to begin in either the prone or left-lateral (LL) position. A total of 181 adult patients undergoing scheduled colonoscopy were stratified by age, gender, body mass index, and experience of the endoscopist. Patients were then randomized 1:1 in permuted blocks. The primary outcome measure was time to cecal intubation and secondary outcome measures included patient comfort that was measured by visual analog scale. RESULTS: There was no benefit from prone starting positioning over conventional left-sided starting positioning. Further, prone starting position led to an increase in time to reach cecum (701 vs. 511 s; P=0.01). This could be in part explained by an increased time to reach transverse colon in patients positioned prone (332 vs. 258 s; P=0.06). Comfort levels were similar between patients positioned prone and LL (4 vs. 4 visual analog scale; P=0.6) although endoscopists found colonoscopies in which patients started prone more technically challenging than if started LL (5 vs. 4; P=0.002). CONCLUSIONS: Prone starting position did not improve time to reach cecum or patient comfort for minimally sedated patients undergoing colonoscopy. The ClinicalTrials.gov identifier is NCT02305706.

Specialist advice for primary care: an evaluation of a gastroenterology email advice service.

Communication between primary and secondary care -physicians is often unreliable and one sided in the form of clinic letters. Alternatively, general practitioners (GPs) may have difficulty contacting an on-call specialist via outdated hospital paging services. At Imperial College Healthcare NHS Trust, a gastroenterology email advice line was set up to promote dialogue and potentially help GPs deal with issues within their practices. The service has been evaluated both objectively through analysis of enquiries and subjectively through a -survey of GPs' views. Analysis showed a very high level of satisfaction among users of the service. There is also good evidence to suggest that the service has helped to streamline patient management and led to the avoidance of some outpatient appointments.

Right Or Left in COLonoscopy (ROLCOL)? A Randomized Controlled Trial of Right- versus Left-Sided Starting Position in Colonoscopy.

OBJECTIVES: Colonoscopy is technically challenging and can cause discomfort for patients. We aimed to test whether right-sided starting position for colonoscopy would result in shorter procedure time and greater patient comfort when compared with conventional left-sided starting position. METHODS: We conducted a randomized controlled trial in which patients were randomized to begin in either the right- (RL) or conventional left-lateral (LL) position. One hundred and sixty-three adult patients undergoing scheduled colonoscopy were stratified by age, gender, body mass index, and experience of the endoscopist. Patients were then randomized 1:1 in permuted blocks. The primary outcome measure was time to cecal intubation and secondary outcome measures included patient comfort that was evaluated by visual analog comfort scale. RESULTS: Median time to reach the cecum was quicker when colonoscopy began with patients positioned RL rather than LL (P=0.0078). Moreover, patients found RL more comfortable than LL (P=0.02). Multiple linear regression confirmed starting position in colonoscopy as an independent determinant of time to reach the cecum (P=0.007). Women and those who had previously undergone abdominal surgery gained the greatest benefit from right-sided positioning (RL vs. LL: 498 vs. 824 s; P=0.03 and 498 vs. 797 s; P=0.006, respectively). CONCLUSIONS: Our study reveals that right-sided positioning at the start of colonoscopy results in more comfortable and quicker procedures. Of the factors identified by multiple linear regression to independently have an impact on time to reach the cecum, only starting position is modifiable. Right-sided starting position may therefore be of benefit in colonoscopy, in particular for women and patients who have previously undergone abdominal surgery.

Mass Spectrometric Analysis of Exhaled Breath for the Identification of Volatile Organic Compound Biomarkers in Esophageal and Gastric Adenocarcinoma.

OBJECTIVE: The present study assessed whether exhaled breath analysis using Selected Ion Flow Tube Mass Spectrometry could distinguish esophageal and gastric adenocarcinoma from noncancer controls. BACKGROUND: The majority of patients with upper gastrointestinal cancer present with advanced disease, resulting in poor long-term survival rates. Novel methods are needed to diagnose potentially curable upper gastrointestinal malignancies. METHODS: A Profile-3 Selected Ion Flow Tube Mass Spectrometry instrument was used for analysis of volatile organic compounds (VOCs) within exhaled breath samples. All study participants had undergone upper gastrointestinal endoscopy on the day of breath sampling. Receiver operating characteristic analysis and a diagnostic risk prediction model were used to assess the discriminatory accuracy of the identified VOCs. RESULTS: Exhaled breath samples were analyzed from 81 patients with esophageal (N = 48) or gastric adenocarcinoma (N = 33) and 129 controls including Barrett's metaplasia (N = 16), benign upper gastrointestinal diseases (N = 62), or a normal upper gastrointestinal tract (N = 51). Twelve VOCs-pentanoic acid, hexanoic acid, phenol, methyl phenol, ethyl phenol, butanal, pentanal, hexanal, heptanal, octanal, nonanal, and decanal-were present at significantly higher concentrations (P < 0.05) in the cancer groups than in the noncancer controls. The area under the ROC curve using these significant VOCs to discriminate esophageal and gastric adenocarcinoma from those with normal upper gastrointestinal tracts was 0.97 and 0.98, respectively. The area under the ROC curve for the model and validation subsets of the diagnostic prediction model was 0.92 ±â€Š0.01 and 0.87 ±â€Š0.03, respectively. CONCLUSIONS: Distinct exhaled breath VOC profiles can distinguish patients with esophageal and gastric adenocarcinoma from noncancer controls.