157 results on '"Lovat LB"'
Search Results
2. PWE-183 Survivin expression increases in the progression to oesophageal adenocarcinoma
- Author
-
Puccio, I, Butt, MA, Rodriguez-Justo, M, Khan, S-U-R, Sehgal, V, Novelli, M, Lovat, LB, and Hamoudi, R
- Published
- 2015
- Full Text
- View/download PDF
3. PWE-182 The effect of nfΚb pathway deregulation on the progression to oesophageal adenocarcinoma through aberrant BCL3 expression
- Author
-
Puccio, I, Rodriguez-Justo, M, Butt, MA, Khan, S-U-R, Novelli, M, Lovat, LB, and Hamoudi, R
- Published
- 2015
- Full Text
- View/download PDF
4. OC-042 The development of a novel endoscopic orthotopic tumour model for oesophageal cancer
- Author
-
Sehgal, V, Butt, MA, Funnell, L, Pye, H, Khan, S, Puccio, I, Sultan, A, Woodhams, J, Mosse, S, Draper, B, Patrick, SP, Kalber, T, Hamoudi, R, Rodriguez-Justo, M, Pule, M, Lythgoe, M, Novelli, M, and Lovat, LB
- Published
- 2015
- Full Text
- View/download PDF
5. OC-037 6 year disease durability outcomes on patients treated with endoscopic therapy for barrett’s related neoplasia from the uk registry
- Author
-
Haidry, R, Lipman, G, Gupta, A, Dunn, J, Smart, H, Bhandari, P, Willert, R, Fullarton, G, di Pietro, M, Gordon, C, Penman, I, Boger, P, Ravi, N, Ang, Y, Novelli, M, and Lovat, LB
- Published
- 2015
- Full Text
- View/download PDF
6. Semi-Automated Annotation tool Outperforms Trained Medical Students and is Comparable to Clinical Expert Performance for Frame-Level Detection of Colorectal Polyps
- Author
-
Eelbode, T, additional, Ahmad, OF, additional, Sinonquel, P, additional, Blakemore Kocadag, T, additional, Narayan, N, additional, Rana, N, additional, Maes, F, additional, Lovat, LB, additional, and Bisschops, R, additional
- Published
- 2021
- Full Text
- View/download PDF
7. Artificial intelligence and computer-aided diagnosis in colonoscopy: current evidence and future directions
- Author
-
Ahmad, OF, Soares, AS, Mazomenos, E, Brandao, P, Vega, R, Seward, E, Stoyanov, D, Chand, M, and Lovat, LB
- Abstract
Computer-aided diagnosis offers a promising solution to reduce variation in colonoscopy performance. Pooled miss rates for polyps are as high as 22%, and associated interval colorectal cancers after colonoscopy are of concern. Optical biopsy, whereby in-vivo classification of polyps based on enhanced imaging replaces histopathology, has not been incorporated into routine practice because it is limited by interobserver variability and generally only meets accepted standards in expert settings. Real-time decision-support software has been developed to detect and characterise polyps, and also to offer feedback on the technical quality of inspection. Some of the current algorithms, particularly with recent advances in artificial intelligence techniques, match human expert performance for optical biopsy. In this Review, we summarise the evidence for clinical applications of computer-aided diagnosis and artificial intelligence in colonoscopy.
- Published
- 2019
8. Improvement over time in outcomes for patients undergoing endoscopic therapy for Barrett's oesophagus-related neoplasia: 6-year experience from the first 500 patients treated in the UK patient registry
- Author
-
Haidry, RJ, Butt, MA, Dunn, JM, Gupta, A, Lipman, G, Smart, HL, Bhandari, P, Smith, L, Willert, R, Fullarton, G, Di Pietro, M, Gordon, C, Penman, I, Barr, H, Patel, P, Kapoor, N, Hoare, J, Narayanasamy, R, Ang, Y, Veitch, A, Ragunath, K, Novelli, M, Lovat, LB, UK RFA Registry, Di Pietro, Massimiliano [0000-0003-4866-7026], and Apollo - University of Cambridge Repository
- Subjects
Adult ,Aged, 80 and over ,Male ,Time Factors ,Esophageal Neoplasms ,Adenocarcinoma ,Middle Aged ,United Kingdom ,Barrett Esophagus ,surgical procedures, operative ,Treatment Outcome ,ENDOSCOPIC PROCEDURES ,Catheter Ablation ,Disease Progression ,Humans ,Female ,Esophagoscopy ,Prospective Studies ,Registries ,BARRETT'S OESOPHAGUS ,OESOPHAGEAL CANCER ,Precancerous Conditions ,Aged ,Follow-Up Studies - Abstract
BACKGROUND: Barrett's oesophagus (BE) is a pre-malignant condition leading to oesophageal adenocarcinoma (OAC). Treatment of neoplasia at an early stage is desirable. Combined endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA) is an alternative to surgery for patients with BE-related neoplasia. METHODS: We examined prospective data from the UK registry of patients undergoing RFA/EMR for BE-related neoplasia from 2008 to 2013. Before RFA, visible lesions were removed by EMR. Thereafter, patients had RFA 3-monthly until all BE was ablated or cancer developed (endpoints). End of treatment biopsies were recommended at around 12 months from first RFA treatment or when endpoints were reached. Outcomes for clearance of dysplasia (CR-D) and BE (CR-IM) at end of treatment were assessed over two time periods (2008-2010 and 2011-2013). Durability of successful treatment and progression to OAC were also evaluated. RESULTS: 508 patients have completed treatment. CR-D and CR-IM improved significantly between the former and later time periods, from 77% and 56% to 92% and 83%, respectively (p
- Published
- 2015
9. PWE-078 Magnification Endoscopy with I-Scan Imaging and Acetic Acid Chromoendoscopy in Barrett’s Oesophagus Improves Neoplasia Detection
- Author
-
Lipman, G, primary, Bisschops, R, additional, Ortiz-Fernández-Sordo, J, additional, Sweis, R, additional, Esteban, JM, additional, Lovat, LB, additional, Ragunath, K, additional, and Haidry, R, additional
- Published
- 2016
- Full Text
- View/download PDF
10. OC-008 Results of a Feasibility Study Comparing APC with RFA After Endoscopic Resection of Early Neoplasia in Barrett’s Oesophagus: The Bride Study (NCT01733719)
- Author
-
Peerally, MF, primary, Barr, H, additional, Lovat, LB, additional, Bhandari, P, additional, Ragunath, K, additional, Smart, H, additional, Harrison, R, additional, Stokes, C, additional, and Decaestecker, J, additional
- Published
- 2016
- Full Text
- View/download PDF
11. PWE-076 Specialist Centre Patient Volume Does Not Impact on Endoscopic Outcomes for Treatment of Barrett’s Dysplasia. Results from The UK Registry
- Author
-
Lipman, G, primary, Gupta, A, additional, Banks, M, additional, Sweis, R, additional, Dunn, JM, additional, Morris, D, additional, Smart, H, additional, Bhandari, P, additional, Willert, RP, additional, Fullarton, G, additional, Morris, AJ, additional, Di Pietro, M, additional, Mundre, P, additional, Gordon, C, additional, Penman, I, additional, Barr, H, additional, Patel, P, additional, Boger, P, additional, Kapoor, N, additional, Mahon, BS, additional, Hoare, J, additional, Narayanasamy, R, additional, O’Toole, D, additional, Ang, Y, additional, Veitch, A, additional, Nylander, D, additional, Dhar, A, additional, Ragunath, K, additional, Leahy, A, additional, Fullard, M, additional, Haidry, R, additional, and Lovat, LB, additional
- Published
- 2016
- Full Text
- View/download PDF
12. PTU-058 Machine Learning Creates A Simple Endoscopic Classification System For Detecting Dysplasia In Barrett’s Oesophagus With I-scan Imaging And Opens The Way To Standardised Training And Assessment Of Competence
- Author
-
Sehgal, V, primary, Rosenfeld, A, additional, Graham, DG, additional, Banks, MR, additional, Haidry, RJ, additional, and Lovat, LB, additional
- Published
- 2014
- Full Text
- View/download PDF
13. Molecular mechanisms of fibrillogenesis and the protective role of amyloid P component: Two possible avenues for therapy
- Author
-
Pepys, MB, Tennent, GA, Booth, DR, Bellotti, V, Lovat, LB, Tan, SY, Persey, MR, Hutchinson, WL, Booth, SE, Madhoo, S, Soutar, AK, Hawkins, PN, VanZylSmit, R, Campistol, JM, Fraser, PE, Radford, SE, Robinson, CV, Sunde, M, Serpell, LC, Blake, CCF, Buxbaum, JN, and FDN, C
- Subjects
mental disorders - Abstract
Amyloid deposits regress when the supply of fibril precursor proteins is sufficiently reduced, indicating that amyloid fibrils are degradable in vim. Serum amyloid P component (SAP), a universal constituent of amyloid deposits, efficiently protects amyloid fibrils from proteolysis in vitro, and may contribute to persistence of amyloid in vivo. Drugs that prevent binding of SAP to amyloid fibrils in vivo should therefore promote regression of amyloid and we are actively seeking such agents. A complementary strategy is identification of critical molecular processes in fibrillogenesis as targets for pharmacological intervention. All amyloidogenic variants of apolipoprotein AI contain an additional positive charge in the N-terminal fibrillogenic region of the protein. This is unlikely to be a coincidence and should be informative about amyloidogenesis by this protein. The two amyloidogenic variants of human lysozyme, caused by the first natural mutations found in its gene, provide a particularly powerful model system because both the crystal structure and folding pathways of wild-type lysozyme are so well characterized. The amyloidogenic variant lysozymes have similar 3D crystal structures to the wild type, but are notably less thermostable. They unfold on heating, lose enzymic activity, and aggregate to form amyloid fibrils in vitro.
- Published
- 1996
14. Nature and specificity of amyloid fibril binding by serum amyloid P component
- Author
-
Lovat, LB, Hohenester, E, Westermark, P, Wood, SP, Pepys, MB, Lovat, LB, Hohenester, E, Westermark, P, Wood, SP, and Pepys, MB
- Published
- 1999
15. Long-term survival in systemic amyloid A amyloidosis complicating Crohn's disease
- Author
-
Lovat, LB, primary, Madhoo, S, additional, Pepys, MB, additional, and Hawkins, PN, additional
- Published
- 1997
- Full Text
- View/download PDF
16. Radiofrequency ablation is effective for the treatment of high-grade dysplasia in Barrett's esophagus after failed photodynamic therapy.
- Author
-
Dunn JM, Banks MR, Oukrif D, Mackenzie GD, Thorpe S, Rodriguez-Justo M, Winstanley A, Bown SG, Novelli MR, and Lovat LB
- Published
- 2011
17. Nutritional Supplements in the Elderly.
- Author
-
Hogarth, MB, Lovat, LB, Marshall, P, Palmer, A, Frost, G, Fletcher, AE, Nicholl, CG, and Bulpitt, CJ
- Published
- 1995
- Full Text
- View/download PDF
18. UK experience of liver transplantation in FAP
- Author
-
Hawkins, PN, Persey, MR, Lovat, LB, Madhoo, S, Stangou, A, McCarthy, M, Heaton, N, Williams, R, and Pepys, MB
- Abstract
Orthotopic liver transplantation (OLT) is the only potentially curative therapy available for patients with TTR-associated FAP but important questions remain about the timing of the procedure and patient selection. FAP is extremely rare in the UK and the supply of donor livers has so far been adequate to meet demand. We report here the UK experience. Nine patients with TTR associated FAP, aged 33-63 yr, have undergone OLT in the UK, 7 of which were performed at King's College Hospital. Evaluation included serial serum amyloid P component (SAP) scintigraphy, neurophysiological tests, non-invasive cardiac investigations and studies of gastrointestinal function. TTR variants were confirmed in each patient, Met30 in 6 cases, Pro52 in 2 cases and Tyr77 in one. Symptomatic FAP had been present for 3-9 years including severe diarrhoea, urinary retention, hypotension, impotence, dysrhythmias, and peripheral neuropathy. One patient with advanced cardiac amyloid (Tyr77) required a combined liver and heart transplant. Surgery at King's College Hospital was uneventful in all 7 cases, including the liver-heart procedure, but the 2 other patients died during and 3 months after surgery (Met30 and Pro52 respectively). The 4 Met30 patients who were grafted more than 16 months ago have experienced substantial improvements in gut, bladder and erectile function, general well-being, and sensori-motor symptoms. Similar progress occurred in the Tyr77 case including the first objective improvement of peripheral neuropathy. SAP scans showed visceral amyloid deposits in 8 patients, all of whom had unsuspected renal involvement. Follow-up scans showed regression of amyloid in some cases, whereas autonomic function improved in all but one case. A patient with TTR Pro52 did not improve at all and died 15 months after surgery. Renal failure occurred post-operatively in one patient and during follow-up in 2 others. Presently 5 OLT recipients are alive 1-20 months after surgery. The heart-liver patient died suddenly at 34 months whilst receiving dialysis. Our results confirm that OLT is effective in TTR-associated FAP but that advanced disease may confer unacceptably high morbidity and mortality. The survival of patients with different TTR variants may not be uniform and the incidence of renal failure is a major concern. Most clinical features of the disease improved but the best results occurred in patients who were transplanted early in the course of the disease. Objective improvement in peripheral nerve function appears to be very slow, a finding that further encourages early transplantation.
- Published
- 1996
- Full Text
- View/download PDF
19. TTR Mutations in 2 patients with a clinical diagnosis of senile cardiac amyloidosis
- Author
-
Persey, MR, Lovat, LB, Booth, DR, Booth, SE, Madhoo, S, Pepys, MB, and Hawkins, PN
- Abstract
Senile cardiac amyloidosis of TTR type is not uncommon in the elderly but is often unrecognised. The diagnosis was made in two elderly patients by specific immunohistochemical studies of amyloid deposits in endomyocardial biopsies that confirmed the presence of TTR. The first patient was a 75 year old woman who was found to have a restrictive cardiomyopathy following presentation with cardiac arrest and the other a West Indian man aged 66 who, unusually, presented with dilated cardiomyopathy. Neither patient had a positive family history of cardiac or other disease. Whole body scintigraphy with I labelled SAP showed no extra-cardiac amyloid deposits in the female patient but surprisingly identified clinically silent amyloid in the kidneys and carpal tunnel region in the male case. Direct double-stranded DNA sequencing of the TTR gene identified point mutations encoding the TTR Ala60 and Ile122 variants respectively, both of which have been previously described in association with hereditary amyloidosis. TTR gene sequencing should be contemplated in all patients with cardiac TTR amyloidosis even when there are no features pointing to an hereditary aetiology. These findings had substantial implications for the relatives of our two cases and raise the possibility that the syndrome of senile cardiac amyloidosis may be associated with TTR variants in other patients.
- Published
- 1996
- Full Text
- View/download PDF
20. SAP scintigraphy in 43 patients with TTR-associated FAP
- Author
-
Hawkins, PN, Rydh, A, Persey, MR, Lovat, LB, Madhoo, S, Suhr, O, and Pepys, MB
- Abstract
Whole body scintigraphy with I-labelled serum amyloid P component (SAP) is a specific, quantitative investigation for evaluating amyloid deposits in vivo . We report here our experience of 69 studies in 43 patients with hereditary TTR-associated amyloidosis. 52 studies were performed in London and 14 in Umea˚. Follow-up scans were scheduled annually. Scans in all 26 patients with symptomatic TTR Met30 associated FAP were diagnostic, demonstrating amyloid deposits in the kidneys, spleen and adrenal glands in 26, 13 and 7 individuals respectively. Although some uptake of tracer was noted in the gut, thyroid and salivary glands, the significance of this is unknown because free radioiodine can also accumulate at these sites. The wholebody amyloid load ranged from small to moderate. Studies in 17 individuals with 11 other amyloidogenic TTR mutations, some of whom were asymptomatic, showed great diversity with respect to presence, distribution and quantity of visceral amyloid as well as associated functional disturbance. Systemic amyloid deposits were very extensive in 3 subjects with TTR Pro52 but were not identified in cases with TTR Glu18, His58, Ala60 and Tyr77. TTR amyloid deposits were identified for the first time in the liver of a patient who had a very atypical long clinical history associated with TTR Pro12. Neural and cardiac amyloid deposits could not be imaged conclusively in any of the 43 cases. Follow-up scans in 7 untreated patients over 1-3 years mostly showed remarkably little evidence of amyloid progression, whilst variable amounts of regression were observed in 6 out of 7 cases whose scans were repeated at least 12 months after orthotopic liver transplantation. SAP scintigraphy is an effective method for identifying and monitoring visceral amyloid deposits in patients with FAP. Most patients have far less systemic amyloid than is usually found in AA and AL types but, nevertheless, the extent of visceral amyloid is usually underestimated clinically. Only one patient studied so far has shown dramatic amyloid progression, suggesting that the disease may often be in a plateau phase by the time of clinical presentation, or that undetectably minor amyloid progression may cause major functional deterioration after a "threshold" disease-causing amount of amyloid has been laid down. Along with the differences in rate of regression following liver transplantation, our results show that the kinetics of TTR amyloid turnover vary substantially between patients. Studies are in progress to examine whether the rate of turnover of amyloid may have prognostic implications following liver transplantation.
- Published
- 1996
- Full Text
- View/download PDF
21. Interventions used to reduce infectious aerosol concentrations in hospitals-a review.
- Author
-
Brady G, Bennin F, De Koning R, Vindrola-Padros C, Clark SE, Tiwari MK, Watt S, Ducci A, Torii R, Morris D, Lloyd-Dehler E, Slann J, Stevenson F, Khadjesari Z, Dehbi HM, Ciric L, Epstein R, Rubin J, Houlihan CF, Hunter R, and Lovat LB
- Abstract
Background: The COVID-19 pandemic highlighted the need for improved infectious aerosol concentrations through interventions that reduce the transmission of airborne infections. The aims of this review were to map the existing literature on interventions used to improve infectious aerosol concentrations in hospitals and understand challenges in their implementation., Methods: We reviewed peer-reviewed articles identified on three databases, MEDLINE, Web of Science, and the Cochrane Library from inception to July 2024. 6417 articles were identified, 160 were reviewed and 18 were included., Findings: Results on aerosol concentration were discussed in terms of three categories: (1) filtration and inactivation of aerosol particles; (2) effect of airflow and ventilation on aerosol concentrations; and (3) improvements or reduction in health conditions. The most common device or method that was outlined by researchers was high efficiency particulate air (HEPA) filters which were able to reduce aerosol concentrations under investigation across the included literature. Some articles were able to demonstrate the effectiveness of interventions in terms of improving health outcomes for patients., Interpretation: The key finding is that infectious aerosol concentration improvement measures based on filtration, inactivation, improved air flow dynamics, and ventilation reduce the likelihood of nosocomial infections. However limitations of such approaches must be considered such as noise pollution and effects on ambient humidity. Whilst these efforts can contribute to improved air quality in hospitals, they should be considered with the other interacting factors such as microclimates, room dimensions and use of chemical products that effect air quality., Funding: This study is funded by the National Institute for Health and Care Research (NIHR) (NIHR205439)., Competing Interests: L.B.L. declared funding from an NIHR PGfAR grant (payment through institution); declared support from the National Institute for Health Research University College London Hospitals Biomedical Research Centre and the Wellcome/EPSRC Centre for Interventional and Surgical Sciences (WEISS); and declared a patent planned. C.V.P. declared funding from an NIHR grant. S.E.C. declared funding from an NIHR grant. F.B. declared funding from University College London. R.H. declared funding from grants and consultancy fees, and declared acting as a Chair for the Transforming Health and Care Systems EU funding board. All other authors had no interests to declare., (© 2024 The Authors.)
- Published
- 2024
- Full Text
- View/download PDF
22. Impact of the COVID-19 pandemic on communal religious worshippers' mental health and the benefits of positive religious coping.
- Author
-
Baggaley RF, Alexander Ho KM, Maltby J, Stone TC, Hoga Á, Johnson C, Merrifield R, and Lovat LB
- Abstract
Background: In the United Kingdom, onsite religious services were halted during COVID-19 lockdowns, which were followed by various levels of restrictions on communal worship including social distancing, mandatory wearing of face masks, adequate ventilation and a ban on congregational singing and chanting. The aim of our study was to evaluate the impact of closures and changes within places of worship in response to the first lockdown in 2020, to assess the effect of the pandemic on religious practice and worshippers' wellbeing and religious coping., Methods: Participants were regular worshippers in the UK, recruited through an online survey using convenience sampling. Respondents were asked about their attitudes to changes to places of worship in the UK and their wellbeing and mental health, including assessment of their risk of depression and anxiety using the Patient Health Questionnaire (PHQ-9) and Generalised Anxiety Disorder Assessment (GAD-7) measures. Questionnaires were completed August to November 2020., Findings: 939 participants were included in the analysis. Median age was 52.7 years and 66.1 % were female. 80.7 % identified as Christian. 165 (19.3 %) had mild, 45 (5.3 %) moderate, 25 (2.9 %) moderately severe and 10 (1.2 %) severe depression, and 192 (22.5 %) had mild, 55 (6.4 %) moderate and 27 (3.2 %) severe anxiety, according to PHQ-9 and GAD-7 scores, respectively. Nearly half (46.4 %) reported that their mood and anxiety levels had worsened and 16.6 % reported that they felt the things they were doing in their lives were not worthwhile. The vast majority of respondents (92.7 %) reported that prayer had helped them cope with the way they had felt during lockdown: 29.2 % and 47.0 % reported that it helped moderately and a great deal, respectively. This 76.2 % had significantly lower levels of moderate/severe depression and anxiety (adjusted odds ratio: depression 0.37 (95%CI 0.22-0.63), anxiety 0.52 (95%CI 0.31-0.88)., Interpretation: Our study demonstrates the significant impact of COVID-19 on communal worshippers' mental health and reinforces the benefits of positive religious coping during the first UK lockdown. Barriers to communal worship participation during lockdowns, including access to appropriate technology, need to be recognised and facilitators identified., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
- Published
- 2024
- Full Text
- View/download PDF
23. Systematic Review and Meta-analysis: The Three-year Post-colonoscopy Colorectal Cancer Rate as per the World Endoscopy Organization Methodology.
- Author
-
Kader R, Hadjinicolaou AV, Burr NE, Bassett P, Ahmad OF, Pedersen L, Chand M, Valori R, Stoyanov D, and Lovat LB
- Abstract
Background & Aims: In 2018, the World Endoscopy Organization (WEO) introduced standardized methods for calculating post-colonoscopy colorectal cancer-3yr rates (PCCRC-3yr). This systematic review aimed to calculate the global PCCRC-3yr according to the WEO methodology, its change over time, and to measure the association between risk factors and PCCRC occurrences., Methods: We searched 5 databases from inception until January 2024 for PCCRC-3yr studies that strictly adhered to the WEO methodology. The overall pooled PCCRC-3yr was calculated. For risk factors and time-trend analyses, the pooled PCCRC-3yr and odds ratios (ORs) of subgroups were compared., Results: Several studies failed to adhere to the WEO methodology. Eight studies from 4 Western European and 2 Northern American countries were included, totalling 220,106 detected-colorectal cancers (CRCs) and 18,148 PCCRCs between 2002 and 2017. The pooled Western World PCCRC-3yr was 7.5% (95% confidence interval [CI], 6.4%-8.7%). The PCCRC-3yr significantly (P < .05) decreased from 7.9% (95% CI, 6.6%-9.4%) in 2006 to 6.7% (95% CI, 6.1%-7.3%) in 2012 (OR, 0.79; 95% CI, 0.72-0.87). There were significantly higher rates for people with inflammatory bowel disease (PCCRC-3yr, 29.3%; OR, 6.17; 95% CI, 4.73-8.06), prior CRC (PCCRC-3yr, 29.8%; OR, 3.03; 95% CI, 1.34-4.72), proximal CRC (PCCRC-3yr, 8.6%; OR, 1.51; 95% CI, 1.41-1.61), diverticular disease (PCCRC 3-yr, 11.6%; OR, 1.74; 95% CI, 1.37-2.10), and female sex (PCCRC-3yr, 7.9%; OR, 1.15; 95% CI, 1.11-1.20)., Conclusion: According to the WEO methodology, the Western World PCCRC-3yr was 7.5%. Reassuringly, this has decreased over time, but further work is required to identify the reasons for PCCRCs, especially in higher-risk groups. We devised a WEO methodology checklist to increase its adoption and standardise the categorization of patients in future PCCRC-3yr studies., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
24. SimCol3D - 3D reconstruction during colonoscopy challenge.
- Author
-
Rau A, Bano S, Jin Y, Azagra P, Morlana J, Kader R, Sanderson E, Matuszewski BJ, Lee JY, Lee DJ, Posner E, Frank N, Elangovan V, Raviteja S, Li Z, Liu J, Lalithkumar S, Islam M, Ren H, Lovat LB, Montiel JMM, and Stoyanov D
- Subjects
- Humans, Colorectal Neoplasms diagnostic imaging, Colonic Polyps diagnostic imaging, Imaging, Three-Dimensional methods, Colonoscopy
- Abstract
Colorectal cancer is one of the most common cancers in the world. While colonoscopy is an effective screening technique, navigating an endoscope through the colon to detect polyps is challenging. A 3D map of the observed surfaces could enhance the identification of unscreened colon tissue and serve as a training platform. However, reconstructing the colon from video footage remains difficult. Learning-based approaches hold promise as robust alternatives, but necessitate extensive datasets. Establishing a benchmark dataset, the 2022 EndoVis sub-challenge SimCol3D aimed to facilitate data-driven depth and pose prediction during colonoscopy. The challenge was hosted as part of MICCAI 2022 in Singapore. Six teams from around the world and representatives from academia and industry participated in the three sub-challenges: synthetic depth prediction, synthetic pose prediction, and real pose prediction. This paper describes the challenge, the submitted methods, and their results. We show that depth prediction from synthetic colonoscopy images is robustly solvable, while pose estimation remains an open research question., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Danail Stoyanov reports financial support was provided by Medtronic plc. Danail Stoyanov reports a relationship with Odin Medical Ltd. that includes: equity or stocks. Laurence Lovat and Rawen Kader report a relationship with Olympus Corporation that includes: consulting or advisory., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
- Full Text
- View/download PDF
25. T staging esophageal tumors with x rays.
- Author
-
Partridge T, Wolfson P, Jiang J, Massimi L, Astolfo A, Djurabekova N, Savvidis S, Jones CJM, Hagen CK, Millard E, Shorrock W, Waltham RM, Haig IG, Bate D, Ho KMA, Mc Bain H, Wilson A, Hogan A, Delaney H, Liyadipita A, Levine AP, Dawas K, Mohammadi B, Qureshi YA, Chouhan MD, Taylor SA, Mughal M, Munro PRT, Endrizzi M, Novelli M, Lovat LB, and Olivo A
- Abstract
With histopathology results typically taking several days, the ability to stage tumors during interventions could provide a step change in various cancer interventions. X-ray technology has advanced significantly in recent years with the introduction of phase-based imaging methods. These have been adapted for use in standard labs rather than specialized facilities such as synchrotrons, and approaches that enable fast 3D scans with conventional x-ray sources have been developed. This opens the possibility to produce 3D images with enhanced soft tissue contrast at a level of detail comparable to histopathology, in times sufficiently short to be compatible with use during surgical interventions. In this paper we discuss the application of one such approach to human esophagi obtained from esophagectomy interventions. We demonstrate that the image quality is sufficiently high to enable tumor T staging based on the x-ray datasets alone. Alongside detection of involved margins with potentially life-saving implications, staging tumors intra-operatively has the potential to change patient pathways, facilitating optimization of therapeutic interventions during the procedure itself. Besides a prospective intra-operative use, the availability of high-quality 3D images of entire esophageal tumors can support histopathological characterization, from enabling "right slice first time" approaches to understanding the histopathology in the full 3D context of the surrounding tumor environment., Competing Interests: AA, EM, WS, RMW, IGH, and DB are Nikon employees, or were Nikon employees at the time this research was carried out. PRTM and AO are named inventors on patents held by UCL protecting the x-ray imaging technology described in this paper. All other authors have no conflicts to declare., (© 2024 The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
26. Response to: Comment on 'Surgical experience and identification of errors in laparoscopic cholecystectomy'.
- Author
-
Humm GL, Peckham-Cooper A, Chang J, Fernandes R, Fakih Gomez N, Mohan H, Nally D, Thaventhiran AJ, Zakeri R, Gupte A, Crosbie J, Wood C, Dawas K, Stoyanov D, and Lovat LB
- Subjects
- Humans, Cholecystectomy, Laparoscopic, Medical Errors
- Published
- 2024
- Full Text
- View/download PDF
27. Using saliva epigenetic data to develop and validate a multivariable predictor of esophageal cancer status.
- Author
-
Stone TC, Ward V, Hogan A, Ho KMA, Wilson A, McBain H, Duku M, Wolfson P, Cheung S, Rosenfeld A, and Lovat LB
- Subjects
- Humans, Saliva, Epigenesis, Genetic, Biomarkers, Tumor genetics, DNA Methylation, Esophageal Neoplasms diagnosis, Esophageal Neoplasms genetics, Esophageal Neoplasms pathology, Adenocarcinoma pathology
- Abstract
Background: Salivary epigenetic biomarkers may detect esophageal cancer. Methods: A total of 256 saliva samples from esophageal adenocarcinoma patients and matched volunteers were analyzed with Illumina EPIC methylation arrays. Three datasets were created, using 64% for discovery, 16% for testing and 20% for validation. Modules of gene-based methylation probes were created using weighted gene coexpression network analysis. Module significance to disease and gene importance to module were determined and a random forest classifier generated using best-scoring gene-related epigenetic probes. A cost-sensitive wrapper algorithm maximized cancer diagnosis. Results: Using age, sex and seven probes, esophageal adenocarcinoma was detected with area under the curve of 0.72 in discovery, 0.73 in testing and 0.75 in validation datasets. Cancer sensitivity was 88% with specificity of 31%. Conclusion: We have demonstrated a potentially clinically viable classifier of esophageal cancer based on saliva methylation.
- Published
- 2024
- Full Text
- View/download PDF
28. Surgical experience and identification of errors in laparoscopic cholecystectomy.
- Author
-
Humm GL, Peckham-Cooper A, Chang J, Fernandes R, Gomez NF, Mohan H, Nally D, Thaventhiran AJ, Zakeri R, Gupte A, Crosbie J, Wood C, Dawas K, Stoyanov D, and Lovat LB
- Subjects
- Humans, Dissection, Gallbladder, Ligation, Reproducibility of Results, Cholecystectomy, Laparoscopic methods
- Abstract
Background: Surgical errors are acts or omissions resulting in negative consequences and/or increased operating time. This study describes surgeon-reported errors in laparoscopic cholecystectomy., Methods: Intraoperative videos were uploaded and annotated on Touch SurgeryTM Enterprise. Participants evaluated videos for severity using a 10-point intraoperative cholecystitis grading score, and errors using Observational Clinical Human Reliability Assessment, which includes skill, consequence, and mechanism classifications., Results: Nine videos were assessed by 8 participants (3 junior (specialist trainee (ST) 3-5), 2 senior trainees (ST6-8), and 3 consultants). Participants identified 550 errors. Positive relationships were seen between total operating time and error count (r2 = 0.284, P < 0.001), intraoperative grade score and error count (r2 = 0.578, P = 0.001), and intraoperative grade score and total operating time (r2 = 0.157, P < 0.001). Error counts differed significantly across intraoperative phases (H(6) = 47.06, P < 0.001), most frequently at dissection of the hepatocystic triangle (total 282; median 33.5 (i.q.r. 23.5-47.8, range 15-63)), ligation/division of cystic structures (total 124; median 13.5 (i.q.r. 12-19.3, range 10-26)), and gallbladder dissection (total 117; median 14.5 (i.q.r. 10.3-18.8, range 6-26)). There were no significant differences in error counts between juniors, seniors, and consultants (H(2) = 0.03, P = 0.987). Errors were classified differently. For dissection of the hepatocystic triangle, thermal injuries (50 in total) were frequently classified as executional, consequential errors; trainees classified thermal injuries as step done with excessive force, speed, depth, distance, time or rotation (29 out of 50), whereas consultants classified them as incorrect orientation (6 out of 50). For ligation/division of cystic structures, inappropriate clipping (60 errors in total), procedural errors were reported by junior trainees (6 out of 60), but not consultants. For gallbladder dissection, inappropriate dissection (20 errors in total) was reported in incorrect planes by consultants and seniors (6 out of 20), but not by juniors. Poor economy of movement (11 errors in total) was reported more by consultants (8 out of 11) than trainees (3 out of 11)., Conclusion: This study suggests that surgical experience influences error interpretation, but the benefits for surgical training are currently unclear., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
29. Automated analysis of intraoperative phase in laparoscopic cholecystectomy: A comparison of one attending surgeon and their residents.
- Author
-
Humm G, Peckham-Cooper A, Hamade A, Wood C, Dawas K, Stoyanov D, and Lovat LB
- Subjects
- Adult, Humans, Dissection, Cholecystectomy, Laparoscopic education, Internship and Residency, Surgeons
- Abstract
Objective: This study compares the intraoperative phase times in laparoscopic cholecystectomy performed by an attending surgeon and supervised residents over 10-years to assess operative times as a marker of performance and any impact of case severity on times., Design: Laparoscopic cholecystectomy videos were uploaded to Touch Surgery™ Enterprise, a combined software and hardware solution for securely recording, storing, and analysing surgical videos, which provide analytics of intraoperative phase times. Case severity and visualisation of the critical view of safety (CVS) were manually assessed using modified 10-point intraoperative gallbladder scoring system (mG10) and CVS scores, respectively. Attending and residents' times were compared unmatched and matched by mG10., Setting: Secondary analysis of anonymized laparoscopic cholecystectomy video, recorded as standard of care., Participants: Adult patients who underwent elective laparoscopic cholecystectomy a single UK hospital. Cases were performed by one attending and their residents., Results: 159 (attending=96, resident=63) laparoscopic cholecystectomy videos and intraoperative phase times were reviewed on Touch Surgery™ Enterprise and analyzed. Attending cases were more challenging (p=0.037). Residents achieved higher CVS scores (p=0.034) and showed longer dissection of hepatocystic triangle (HCT) times (p=0.012) in more challenging cases. Residents' total operative time (p=0.001) and dissection of HCT (p=0.002) times exceeded the attending's in low-severity matched cases (mG10=1). Residents' total operative times (p<0.001), port insertion/gallbladder exposure (p=0.032), and dissection of HCT (p<0.001) exceeded the attending's in matched cases (mG10=2). Residents' total operative (p<0.001), dissection of HCT (p<0.001), and gallbladder dissection (p=0.010) times exceeded the attendings in unmatched cases., Conclusions: Residents' total operative and dissection of HCT times significantly exceeded the attending's unmatched cases and low-severity matched cases which could suggest training need, however, also reflects an expected assessment of competence, and validates time as a marker of performance., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
30. Polyp characterization using deep learning and a publicly accessible polyp video database.
- Author
-
Kader R, Cid-Mejias A, Brandao P, Islam S, Hebbar S, Puyal JG, Ahmad OF, Hussein M, Toth D, Mountney P, Seward E, Vega R, Stoyanov D, and Lovat LB
- Subjects
- Humans, Colonoscopy methods, Narrow Band Imaging methods, Colonic Polyps diagnostic imaging, Colonic Polyps pathology, Colorectal Neoplasms pathology, Deep Learning, Adenoma diagnostic imaging, Adenoma pathology
- Abstract
Objectives: Convolutional neural networks (CNN) for computer-aided diagnosis of polyps are often trained using high-quality still images in a single chromoendoscopy imaging modality with sessile serrated lesions (SSLs) often excluded. This study developed a CNN from videos to classify polyps as adenomatous or nonadenomatous using standard narrow-band imaging (NBI) and NBI-near focus (NBI-NF) and created a publicly accessible polyp video database., Methods: We trained a CNN with 16,832 high and moderate quality frames from 229 polyp videos (56 SSLs). It was evaluated with 222 polyp videos (36 SSLs) across two test-sets. Test-set I consists of 14,320 frames (157 polyps, 111 diminutive). Test-set II, which is publicly accessible, 3317 video frames (65 polyps, 41 diminutive), which was benchmarked with three expert and three nonexpert endoscopists., Results: Sensitivity for adenoma characterization was 91.6% in test-set I and 89.7% in test-set II. Specificity was 91.9% and 88.5%. Sensitivity for diminutive polyps was 89.9% and 87.5%; specificity 90.5% and 88.2%. In NBI-NF, sensitivity was 89.4% and 89.5%, with a specificity of 94.7% and 83.3%. In NBI, sensitivity was 85.3% and 91.7%, with a specificity of 87.5% and 90.0%, respectively. The CNN achieved preservation and incorporation of valuable endoscopic innovations (PIVI)-1 and PIVI-2 thresholds for each test-set. In the benchmarking of test-set II, the CNN was significantly more accurate than nonexperts (13.8% difference [95% confidence interval 3.2-23.6], P = 0.01) with no significant difference with experts., Conclusions: A single CNN can differentiate adenomas from SSLs and hyperplastic polyps in both NBI and NBI-NF. A publicly accessible NBI polyp video database was created and benchmarked., (© 2023 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)
- Published
- 2023
- Full Text
- View/download PDF
31. Automated colonoscopy withdrawal phase duration estimation using cecum detection and surgical tasks classification.
- Author
-
De Carvalho T, Kader R, Brandao P, González-Bueno Puyal J, Lovat LB, Mountney P, and Stoyanov D
- Abstract
Colorectal cancer is the third most common type of cancer with almost two million new cases worldwide. They develop from neoplastic polyps, most commonly adenomas, which can be removed during colonoscopy to prevent colorectal cancer from occurring. Unfortunately, up to a quarter of polyps are missed during colonoscopies. Studies have shown that polyp detection during a procedure correlates with the time spent searching for polyps, called the withdrawal time. The different phases of the procedure (cleaning, therapeutic, and exploration phases) make it difficult to precisely measure the withdrawal time, which should only include the exploration phase. Separating this from the other phases requires manual time measurement during the procedure which is rarely performed. In this study, we propose a method to automatically detect the cecum, which is the start of the withdrawal phase, and to classify the different phases of the colonoscopy, which allows precise estimation of the final withdrawal time. This is achieved using a Resnet for both detection and classification trained with two public datasets and a private dataset composed of 96 full procedures. Out of 19 testing procedures, 18 have their withdrawal time correctly estimated, with a mean error of 5.52 seconds per minute per procedure., Competing Interests: D.S: Odin Vision Ltd (I, S), D.S: Digital Surgery Ltd (E), L.L: Odin Vision Ltd (I)., (Published by Optica Publishing Group under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.)
- Published
- 2023
- Full Text
- View/download PDF
32. Lynch syndrome: from detection to treatment.
- Author
-
Williams MH, Hadjinicolaou AV, Norton BC, Kader R, and Lovat LB
- Abstract
Lynch syndrome (LS) is an inherited cancer predisposition syndrome associated with high lifetime risk of developing tumours, most notably colorectal and endometrial. It arises in the context of pathogenic germline variants in one of the mismatch repair genes, that are necessary to maintain genomic stability. LS remains underdiagnosed in the population despite national recommendations for empirical testing in all new colorectal and endometrial cancer cases. There are now well-established colorectal cancer surveillance programmes, but the high rate of interval cancers identified, coupled with a paucity of high-quality evidence for extra-colonic cancer surveillance, means there is still much that can be achieved in diagnosis, risk-stratification and management. The widespread adoption of preventative pharmacological measures is on the horizon and there are exciting advances in the role of immunotherapy and anti-cancer vaccines for treatment of these highly immunogenic LS-associated tumours. In this review, we explore the current landscape and future perspectives for the identification, risk stratification and optimised management of LS with a focus on the gastrointestinal system. We highlight the current guidelines on diagnosis, surveillance, prevention and treatment and link molecular disease mechanisms to clinical practice recommendations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Williams, Hadjinicolaou, Norton, Kader and Lovat.)
- Published
- 2023
- Full Text
- View/download PDF
33. Identifying key mechanisms leading to visual recognition errors for missed colorectal polyps using eye-tracking technology.
- Author
-
Ahmad OF, Mazomenos E, Chadebecq F, Kader R, Hussein M, Haidry RJ, Puyal JG, Brandao P, Toth D, Mountney P, Seward E, Vega R, Stoyanov D, and Lovat LB
- Subjects
- Humans, Eye-Tracking Technology, Artificial Intelligence, Colonoscopy methods, Colonic Polyps diagnosis, Colonic Polyps pathology, Colorectal Neoplasms diagnosis, Colorectal Neoplasms pathology
- Abstract
Background and Aim: Lack of visual recognition of colorectal polyps may lead to interval cancers. The mechanisms contributing to perceptual variation, particularly for subtle and advanced colorectal neoplasia, have scarcely been investigated. We aimed to evaluate visual recognition errors and provide novel mechanistic insights., Methods: Eleven participants (seven trainees and four medical students) evaluated images from the UCL polyp perception dataset, containing 25 polyps, using eye-tracking equipment. Gaze errors were defined as those where the lesion was not observed according to eye-tracking technology. Cognitive errors occurred when lesions were observed but not recognized as polyps by participants. A video study was also performed including 39 subtle polyps, where polyp recognition performance was compared with a convolutional neural network., Results: Cognitive errors occurred more frequently than gaze errors overall (65.6%), with a significantly higher proportion in trainees (P = 0.0264). In the video validation, the convolutional neural network detected significantly more polyps than trainees and medical students, with per-polyp sensitivities of 79.5%, 30.0%, and 15.4%, respectively., Conclusions: Cognitive errors were the most common reason for visual recognition errors. The impact of interventions such as artificial intelligence, particularly on different types of perceptual errors, needs further investigation including potential effects on learning curves. To facilitate future research, a publicly accessible visual perception colonoscopy polyp database was created., (© 2023 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
34. Response to: 'Use of portable air purifiers to reduce aerosols in hospital settings and cut down the clinical backlog'.
- Author
-
Salmonsmith J, Ducci A, Balachandran R, Guo L, Torii R, Houlihan C, Epstein R, Rubin J, Tiwari MK, and Lovat LB
- Subjects
- Particulate Matter, Particle Size, Aerosols, Air Filters
- Published
- 2023
- Full Text
- View/download PDF
35. Computer-aided characterization of early cancer in Barrett's esophagus on i-scan magnification imaging: a multicenter international study.
- Author
-
Hussein M, Lines D, González-Bueno Puyal J, Kader R, Bowman N, Sehgal V, Toth D, Ahmad OF, Everson M, Esteban JM, Bisschops R, Banks M, Haefner M, Mountney P, Stoyanov D, Lovat LB, and Haidry R
- Subjects
- Humans, Esophagoscopy methods, Hyperplasia, Computers, Barrett Esophagus diagnosis, Esophageal Neoplasms diagnostic imaging
- Abstract
Background and Aims: We aimed to develop a computer-aided characterization system that could support the diagnosis of dysplasia in Barrett's esophagus (BE) on magnification endoscopy., Methods: Videos were collected in high-definition magnification white-light and virtual chromoendoscopy with i-scan (Pentax Hoya, Japan) imaging in patients with dysplastic and nondysplastic BE (NDBE) from 4 centers. We trained a neural network with a Resnet101 architecture to classify frames as dysplastic or nondysplastic. The network was tested on 3 different scenarios: high-quality still images, all available video frames, and a selected sequence within each video., Results: Fifty-seven patients, each with videos of magnification areas of BE (34 dysplasia, 23 NDBE), were included. Performance was evaluated by a leave-1-patient-out cross-validation method. In all, 60,174 (39,347 dysplasia, 20,827 NDBE) magnification video frames were used to train the network. The testing set included 49,726 i-scan-3/optical enhancement magnification frames. On 350 high-quality still images, the network achieved a sensitivity of 94%, specificity of 86%, and area under the receiver operator curve (AUROC) of 96%. On all 49,726 available video frames, the network achieved a sensitivity of 92%, specificity of 82%, and AUROC of 95%. On a selected sequence of frames per case (total of 11,471 frames), we used an exponentially weighted moving average of classifications on consecutive frames to characterize dysplasia. The network achieved a sensitivity of 92%, specificity of 84%, and AUROC of 96%. The mean assessment speed per frame was 0.0135 seconds (SD ± 0.006)., Conclusion: Our network can characterize BE dysplasia with high accuracy and speed on high-quality magnification images and sequence of video frames, moving it toward real-time automated diagnosis., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
36. Artificial intelligence and automation in endoscopy and surgery.
- Author
-
Chadebecq F, Lovat LB, and Stoyanov D
- Subjects
- Humans, Endoscopy, Gastrointestinal, Diagnostic Imaging, Automation, Artificial Intelligence, Endoscopy methods
- Abstract
Modern endoscopy relies on digital technology, from high-resolution imaging sensors and displays to electronics connecting configurable illumination and actuation systems for robotic articulation. In addition to enabling more effective diagnostic and therapeutic interventions, the digitization of the procedural toolset enables video data capture of the internal human anatomy at unprecedented levels. Interventional video data encapsulate functional and structural information about a patient's anatomy as well as events, activity and action logs about the surgical process. This detailed but difficult-to-interpret record from endoscopic procedures can be linked to preoperative and postoperative records or patient imaging information. Rapid advances in artificial intelligence, especially in supervised deep learning, can utilize data from endoscopic procedures to develop systems for assisting procedures leading to computer-assisted interventions that can enable better navigation during procedures, automation of image interpretation and robotically assisted tool manipulation. In this Perspective, we summarize state-of-the-art artificial intelligence for computer-assisted interventions in gastroenterology and surgery., (© 2022. Crown.)
- Published
- 2023
- Full Text
- View/download PDF
37. Development and validation of a multivariable risk factor questionnaire to detect oesophageal cancer in 2-week wait patients.
- Author
-
Ho KMA, Rosenfeld A, Hogan Á, McBain H, Duku M, Wolfson PB, Wilson A, Cheung SM, Hennelly L, Macabodbod L, Graham DG, Sehgal V, Banerjee A, and Lovat LB
- Subjects
- Humans, Prospective Studies, Pandemics, Cross-Sectional Studies, State Medicine, Risk Factors, COVID-19, Esophageal Neoplasms
- Abstract
Introduction: Oesophageal cancer is associated with poor health outcomes. Upper GI (UGI) endoscopy is the gold standard for diagnosis but is associated with patient discomfort and low yield for cancer. We used a machine learning approach to create a model which predicted oesophageal cancer based on questionnaire responses., Methods: We used data from 2 separate prospective cross-sectional studies: the Saliva to Predict rIsk of disease using Transcriptomics and epigenetics (SPIT) study and predicting RIsk of diSease using detailed Questionnaires (RISQ) study. We recruited patients from National Health Service (NHS) suspected cancer pathways as well as patients with known cancer. We identified patient characteristics and questionnaire responses which were most associated with the development of oesophageal cancer. Using the SPIT dataset, we trained seven different machine learning models, selecting the best area under the receiver operator curve (AUC) to create our final model. We further applied a cost function to maximise cancer detection. We then independently validated the model using the RISQ dataset., Results: 807 patients were included in model training and testing, split in a 70:30 ratio. 294 patients were included in model validation. The best model during training was regularised logistic regression using 17 features (median AUC: 0.81, interquartile range (IQR): 0.69-0.85). For testing and validation datasets, the model achieved an AUC of 0.71 (95% CI: 0.61-0.81) and 0.92 (95% CI: 0.88-0.96) respectively. At a set cut off, our model achieved a sensitivity of 97.6% and specificity of 59.1%. We additionally piloted the model in 12 patients with gastric cancer; 9/12 (75%) of patients were correctly classified., Conclusions: We have developed and validated a risk stratification tool using a questionnaire approach. This could aid prioritising patients at high risk of having oesophageal cancer for endoscopy. Our tool could help address endoscopic backlogs caused by the COVID-19 pandemic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
38. Minimally invasive endoscopic therapies for gastro-oesophageal reflux disease.
- Author
-
Aslam N, Telese A, Sehgal V, Sweis R, Lovat LB, and Haidry R
- Abstract
The prevalence of the gastro-oesophageal reflux disease (GORD) in the western world is increasing. Uncontrolled GORD can lead to harmful long-term sequela such as oesophagitis, stricture formation, Barrett's oesophagus and oesophageal adenocarcinoma. Moreover, GORD has been shown to negatively impact quality of life. The current treatment paradigm for GORD consists of lifestyle modification, pharmacological control of gastric acid secretion or antireflux surgery. In recent years, several minimally invasive antireflux endoscopic therapies (ARET) have been developed which may play a role in bridging the unmet therapeutic gap between the medical and surgical treatment options. To ensure optimal patient outcomes following ARET, considered patient selection is crucial, which requires a mechanistic understanding of individual ARET options. Here, we will discuss the differences between ARETs along with an overview of the current evidence base. We also outline future research priorities that will help refine the future role of ARET., Competing Interests: Competing interests: RH receives educational grants to support research infrastructure from Medtronic. Cook endoscopy (fellowship support), Pentax Europe, C2 therapeutics, Beamline diagnostic and Fractyl. VS receives honorarium for professional services from Pentax Europe, Medtronic, Astra Zeneca and Pharmacosmos. RS receives honoraria for running course and speaking at symposia for Medtronic, Johnson & Johnson, Falk Pharma, Medispar. HE is also on the advisory board for Johnson and Johnson and Falk Pharma., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
- Full Text
- View/download PDF
39. Face Mask Acceptability for Communal Religious Worship During the COVID-19 Pandemic in the United Kingdom: Results from the CONFESS Study.
- Author
-
Ho KMA, Baggaley RF, Stone TC, Hogan Á, Kabir Y, Johnson C, Merrifield R, and Lovat LB
- Subjects
- Female, Humans, Middle Aged, Male, Cross-Sectional Studies, Pandemics prevention & control, United Kingdom, Masks, COVID-19 prevention & control
- Abstract
The COVID-19 pandemic has led to restrictions such as social distancing and mandatory wearing of face masks. Singing and religious gatherings have been linked to infection clusters, and between 2020 and 2021 indoor congregational singing and chanting were prohibited in the United Kingdom. We evaluated attitudes to face mask use and their acceptability as well as changes within places of worship since their reopening in July up to autumn 2020. In this cross-sectional study, participants were recruited using convenience sampling through selective targeting of religious organisations and social media. Participants self-enrolled and completed an online questionnaire, which included open and closed questions. We used multivariable logistic regression to identify factors associated with face mask acceptability. We performed thematic analysis to evaluate responses to open questions. A total of 939 participants were included in the analysis. Median age was 52.7 years and 66.1% were female, while 80.7% identified as Christian. A majority (672/861; 78.0%) of participants would find it acceptable to wear a face mask and reduce their singing or chanting volume if required, even though 428/681 (49.1%) found face masks to be uncomfortable. Multivariable regression found that younger age was associated with a higher acceptability of face masks (adjusted OR (aOR): 0.98 (95% confidence interval (95% CI) 0.96-1.00), p = 0.0218). The majority of respondents stated that religious services had become shorter, attended by fewer people and with reduced singing or chanting. Most (869/893, 97.3%) stated their place of worship complied with government guidelines, with 803/887 (90.5%) reported that their place of worship enforced face mask wearing and 793/887 (89.4%) at least moderately happy with precaution measures. Our study demonstrates the significant impact of COVID-19 in places of worship but a high degree of compliance with guidelines. Face masks, despite practical difficulties, appeared to be more acceptable if there was an incentive of being able to sing and chant., (© 2022. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
40. Interobserver Variability in the Assessment of Fluorescence Angiography in the Colon.
- Author
-
Soares AS, Clancy NT, Bano S, Raza I, Diana M, Lovat LB, Stoyanov D, and Chand M
- Subjects
- Humans, Fluorescein Angiography methods, Observer Variation, Indocyanine Green, Anastomosis, Surgical methods, Anastomotic Leak, Coloring Agents, Colorectal Neoplasms surgery
- Abstract
Background: Fluorescence angiography in colorectal surgery is a technique that may lead to lower anastomotic leak rates. However, the interpretation of the fluorescent signal is not standardised and there is a paucity of data regarding interobserver agreement. The aim of this study is to assess interobserver variability in selection of the transection point during fluorescence angiography before anastomosis., Methods: An online survey with still images of fluorescence angiography was distributed through colorectal surgery channels containing images from 13 patients where several areas for transection were displayed to be chosen by raters. Agreement was assessed overall and between pre-planned rater cohorts (experts vs non-experts; trainees vs consultants; colorectal specialists vs non colorectal specialists), using Fleiss' kappa statistic., Results: 101 raters had complete image ratings. No significant difference was found between raters when choosing a point of optimal bowel transection based on fluorescence angiography still images. There was no difference between pre-planned cohorts analysed (experts vs non-experts; trainees vs consultants; colorectal specialists vs non colorectal specialists). Agreement between these cohorts was poor (<.26)., Conclusion: Whilst there is no learning curve for the technical adoption of FA, understanding the fluorescent signal characteristics is key to successful use. We found significant variation exists in interpretation of static fluorescence angiography data. Further efforts should be employed to standardise fluorescence angiography assessment.
- Published
- 2023
- Full Text
- View/download PDF
41. Use of portable air purifiers to reduce aerosols in hospital settings and cut down the clinical backlog.
- Author
-
Salmonsmith J, Ducci A, Balachandran R, Guo L, Torii R, Houlihan C, Epstein R, Rubin J, Tiwari MK, and Lovat LB
- Subjects
- Humans, SARS-CoV-2, State Medicine, Respiratory Aerosols and Droplets, Hospitals, COVID-19, Air Filters
- Abstract
SARS-CoV-2 has severely affected capacity in the National Health Service (NHS), and waiting lists are markedly increasing due to downtime of up to 50 min between patient consultations/procedures, to reduce the risk of infection. Ventilation accelerates this air cleaning, but retroactively installing built-in mechanical ventilation is often cost-prohibitive. We investigated the effect of using portable air cleaners (PAC), a low-energy and low-cost alternative, to reduce the concentration of aerosols in typical patient consultation/procedure environments. The experimental setup consisted of an aerosol generator, which mimicked the subject affected by SARS-CoV-19, and an aerosol detector, representing a subject who could potentially contract SARS-CoV-19. Experiments of aerosol dispersion and clearing were undertaken in situ in a variety of rooms with two different types of PAC in various combinations and positions. Correct use of PAC can reduce the clearance half-life of aerosols by 82% compared to the same indoor-environment without any ventilation, and at a broadly equivalent rate to built-in mechanical ventilation. In addition, the highest level of aerosol concentration measured when using PAC remains at least 46% lower than that when no mitigation is used, even if the PAC's operation is impeded due to placement under a table. The use of PAC leads to significant reductions in the level of aerosol concentration, associated with transmission of droplet-based airborne diseases. This could enable NHS departments to reduce the downtime between consultations/procedures.
- Published
- 2023
- Full Text
- View/download PDF
42. Factors influencing participation in randomised clinical trials among patients with early Barrett's neoplasia: a multicentre interview study.
- Author
-
Peerally MF, Jackson C, Bhandari P, Ragunath K, Barr H, Stokes C, Haidry R, Lovat LB, Smart H, and De Caestecker J
- Subjects
- Humans, Neoplasm Recurrence, Local, Qualitative Research, Randomized Controlled Trials as Topic, Barrett Esophagus surgery, Esophageal Neoplasms surgery, Precancerous Conditions
- Abstract
Objectives: Strong recruitment and retention into randomised controlled trials involving invasive therapies is a matter of priority to ensure better achievement of trial aims. The BRIDE (Barrett's Randomised Intervention for Dysplasia by Endoscopy) Study investigated the feasibility of undertaking a multicentre randomised controlled trial comparing argon plasma coagulation and radiofrequency ablation, following endoscopic resection, for the management of early Barrett's neoplasia. This paper aims to identify factors influencing patients' participation in the BRIDE Study and determine their views regarding acceptability of a potential future trial comparing surgery with endotherapy., Design: A semistructured telephone interview study was performed, including both patients who accepted and declined to participate in the BRIDE trial. Interview data were analysed using the constant comparison approach to identify recurring themes., Setting: Interview participants were recruited from across six UK tertiary centres where the BRIDE trial was conducted., Participants: We interviewed 18 participants, including 11 participants in the BRIDE trial and 7 who declined., Results: Four themes were identified centred around interviewees' decision to accept or decline participation in the BRIDE trial and a potential future trial comparing endotherapy with surgery: (1) influence of the recruitment process and participant-recruiter relationship; (2) participants' views of the design and aim of the study; (3) conditional altruism as a determining factor and (4) participants' perceptions of surgical risks versus less invasive treatments., Conclusion: We identified four main influences to optimising recruitment and retention to a randomised controlled trial comparing endotherapies in patients with early Barrett's-related neoplasia. These findings highlight the importance of qualitative research to inform the design of larger randomised controlled trials., Competing Interests: Competing interests: KR received educational grants from Erbe and Medtronic. RH received research infrastructure support from Medtronic, Cook Endoscopy and Pentax Europe. LBL received research infrastructure support from Medtronic. All other authors disclosed no financial relationships relevant to this article., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)
- Published
- 2023
- Full Text
- View/download PDF
43. Author response to: The impact of virtual-reality simulation training on operative performance in laparoscopic cholecystectomy: meta-analysis of randomized clinical trials.
- Author
-
Humm G, Mohan H, Fleming C, Harries R, Wood C, Dawas K, Stoyanov D, and Lovat LB
- Subjects
- Humans, Randomized Controlled Trials as Topic, Cholecystectomy, Laparoscopic, Simulation Training, Virtual Reality
- Published
- 2022
- Full Text
- View/download PDF
44. Endoscopic eradication therapy for Barrett's esophagus-related neoplasia: a final 10-year report from the UK National HALO Radiofrequency Ablation Registry.
- Author
-
Wolfson P, Ho KMA, Wilson A, McBain H, Hogan A, Lipman G, Dunn J, Haidry R, Novelli M, Olivo A, and Lovat LB
- Subjects
- Esophagoscopy, Humans, Metaplasia, Neoplasm Recurrence, Local epidemiology, Neoplasm Recurrence, Local surgery, Registries, Treatment Outcome, United Kingdom epidemiology, Adenocarcinoma pathology, Adenocarcinoma surgery, Barrett Esophagus pathology, Barrett Esophagus surgery, Catheter Ablation, Esophageal Neoplasms pathology, Esophageal Neoplasms surgery
- Abstract
Background and Aims: Long-term durability data for effectiveness of radiofrequency ablation (RFA) to prevent esophageal adenocarcinoma in patients with dysplastic Barrett's esophagus (BE) are lacking., Methods: We prospectively collected data from 2535 patients with BE (mean length, 5.2 cm; range, 1-20) and neoplasia (20% low-grade dysplasia, 54% high-grade dysplasia, 26% intramucosal carcinoma) who underwent RFA therapy across 28 UK hospitals. We assessed rates of invasive cancer and performed detailed analyses of 1175 patients to assess clearance rates of dysplasia (CR-D) and intestinal metaplasia (CR-IM) within 2 years of starting RFA therapy. We assessed relapses and rates of return to CR-D (CR-D2) and CR-IM (CR-IM2) after further therapy. CR-D and CR-IM were confirmed by an absence of dysplasia and intestinal metaplasia on biopsy samples taken at 2 consecutive endoscopies., Results: Ten years after starting treatment, the Kaplan-Meier (KM) cancer rate was 4.1% with a crude incidence rate of .52 per 100 patient-years. CR-D and CR-IM after 2 years of therapy were 88% and 62.6%, respectively. KM relapse rates were 5.9% from CR-D and 18.7% from CR-IM at 8 years, with most occurring in the first 2 years. Both were successfully retreated with rates of CR-D2 of 63.4% and CR-IM2 of 70.0% 2 years after retreatment. EMR before RFA increased the likelihood of rescue EMR from 17.2% to 41.7% but did not affect the rate of CR-D, whereas rescue EMR after RFA commenced reduced CR-D from 91.4% to 79.7% (χ
2 P < .001)., Conclusions: RFA treatment is effective and durable to prevent esophageal adenocarcinoma. Most treatment relapses occur early and can be successfully retreated., (Copyright © 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
- Full Text
- View/download PDF
45. The impact of virtual reality simulation training on operative performance in laparoscopic cholecystectomy: meta-analysis of randomized clinical trials.
- Author
-
Humm G, Mohan H, Fleming C, Harries R, Wood C, Dawas K, Stoyanov D, and Lovat LB
- Subjects
- Animals, Humans, Randomized Controlled Trials as Topic, Swine, Cholecystectomy, Laparoscopic, Laparoscopy education, Simulation Training methods, Virtual Reality
- Abstract
Background: Simulation training can improve the learning curve of surgical trainees. This research aimed to systematically review randomized clinical trials (RCT) evaluating the performance of junior surgical trainees following virtual reality training (VRT) and other training methods in laparoscopic cholecystectomy., Methods: MEDLINE (PubMed), Embase (Ovid SP), Web of Science, Scopus and LILACS were searched for trials randomizing participants to VRT or no additional training (NAT) or simulation training (ST). Outcomes of interest were the reported performance using global rating scores (GRS), the Objective Structured Assessment of Technical Skill (OSATS) and Global Operative Assessment of Laparoscopic Skills (GOALS), error counts and time to completion of task during laparoscopic cholecystectomy on either porcine models or humans. Study quality was assessed using the Cochrane Risk of Bias Tool. PROSPERO ID: CRD42020208499., Results: A total of 351 titles/abstracts were screened and 96 full texts were reviewed. Eighteen RCT were included and 15 manuscripts had data available for meta-analysis. Thirteen studies compared VRT and NAT, and 4 studies compared VRT and ST. One study compared VRT with NAT and ST and reported GRS only. Meta-analysis showed OSATS score (mean difference (MD) 6.22, 95%CI 3.81 to 8.36, P < 0.001) and time to completion of task (MD -8.35 min, 95%CI 13.10 to 3.60, P = <0.001) significantly improved after VRT compared with NAT. No significant difference was found in GOALS score. No significant differences were found between VRT and ST groups. Intraoperative errors were reported as reduced in VRT groups compared with NAT but were not suitable for meta-analysis., Conclusion: Meta-analysis suggests that performance measured by OSATS and time to completion of task is improved with VRT compared with NAT for junior trainee in laparoscopic cholecystectomy. However, conclusions are limited by methodological heterogeneity and more research is needed to quantify the potential benefit to surgical training., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
46. A new artificial intelligence system successfully detects and localises early neoplasia in Barrett's esophagus by using convolutional neural networks.
- Author
-
Hussein M, González-Bueno Puyal J, Lines D, Sehgal V, Toth D, Ahmad OF, Kader R, Everson M, Lipman G, Fernandez-Sordo JO, Ragunath K, Esteban JM, Bisschops R, Banks M, Haefner M, Mountney P, Stoyanov D, Lovat LB, and Haidry R
- Subjects
- Artificial Intelligence, Biopsy methods, Humans, Neural Networks, Computer, Barrett Esophagus diagnostic imaging, Barrett Esophagus pathology, Esophageal Neoplasms diagnostic imaging, Esophageal Neoplasms pathology
- Abstract
Background and Aims: Seattle protocol biopsies for Barrett's Esophagus (BE) surveillance are labour intensive with low compliance. Dysplasia detection rates vary, leading to missed lesions. This can potentially be offset with computer aided detection. We have developed convolutional neural networks (CNNs) to identify areas of dysplasia and where to target biopsy., Methods: 119 Videos were collected in high-definition white light and optical chromoendoscopy with i-scan (Pentax Hoya, Japan) imaging in patients with dysplastic and non-dysplastic BE (NDBE). We trained an indirectly supervised CNN to classify images as dysplastic/non-dysplastic using whole video annotations to minimise selection bias and maximise accuracy. The CNN was trained using 148,936 video frames (31 dysplastic patients, 31 NDBE, two normal esophagus), validated on 25,161 images from 11 patient videos and tested on 264 iscan-1 images from 28 dysplastic and 16 NDBE patients which included expert delineations. To localise targeted biopsies/delineations, a second directly supervised CNN was generated based on expert delineations of 94 dysplastic images from 30 patients. This was tested on 86 i-scan one images from 28 dysplastic patients., Findings: The indirectly supervised CNN achieved a per image sensitivity in the test set of 91%, specificity 79%, area under receiver operator curve of 93% to detect dysplasia. Per-lesion sensitivity was 100%. Mean assessment speed was 48 frames per second (fps). 97% of targeted biopsy predictions matched expert and histological assessment at 56 fps. The artificial intelligence system performed better than six endoscopists., Interpretation: Our CNNs classify and localise dysplastic Barrett's Esophagus potentially supporting endoscopists during surveillance., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)
- Published
- 2022
- Full Text
- View/download PDF
47. Multisensor perfusion assessment cohort study: Preliminary evidence toward a standardized assessment of indocyanine green fluorescence in colorectal surgery.
- Author
-
Soares AS, Bano S, Clancy NT, Stoyanov D, Lovat LB, and Chand M
- Subjects
- Anastomosis, Surgical methods, Anastomotic Leak diagnosis, Anastomotic Leak etiology, Anastomotic Leak prevention & control, Cohort Studies, Fluorescein Angiography methods, Humans, Indocyanine Green, Perfusion, Prospective Studies, Colorectal Neoplasms surgery, Colorectal Surgery
- Abstract
Background: Traditional methods of assessing colonic perfusion are based on the surgeon's visual inspection of tissue. Fluorescence angiography provides qualitative information, but there remains disagreement on how the observed signal should be interpreted. It is unclear whether fluorescence correlates with physiological properties of the tissue, such as tissue oxygen saturation. The aim of this study was to correlate fluorescence intensity and colonic tissue oxygen saturation., Methods: Prospective cohort study performed in a single academic tertiary referral center. Patients undergoing colorectal surgery who required an anastomosis underwent dual-modality perfusion assessment of a segment of bowel before transection and creation of the anastomosis, using near-infrared and multispectral imaging. Perfusion was assessed using maximal fluorescence intensity measurement during fluorescence angiography, and its correlation with tissue oxygen saturation was calculated., Results: In total, 18 patients were included. Maximal fluorescence intensity occurred at a mean of 101 seconds after indocyanine green injection. The correlation coefficient was 0.73 (95% confidence interval of 0.65-0.79) with P < .0001, showing a statistically significant strong positive correlation between normalized fluorescence intensity and tissue oxygen saturation. The use of time averaging improved the correlation coefficient to 0.78., Conclusion: Fluorescence intensity is a potential surrogate for tissue oxygenation. This is expected to lead to improved decision making when transecting the bowel and, consequently, a reduction in anastomotic leak rates. A larger, phase II study is needed to confirm this result and form the basis of computational algorithms to infer biological or physiological information from the fluorescence imaging data., (Copyright © 2022. Published by Elsevier Inc.)
- Published
- 2022
- Full Text
- View/download PDF
48. Performance of artificial intelligence for detection of subtle and advanced colorectal neoplasia.
- Author
-
Ahmad OF, González-Bueno Puyal J, Brandao P, Kader R, Abbasi F, Hussein M, Haidry RJ, Toth D, Mountney P, Seward E, Vega R, Stoyanov D, and Lovat LB
- Subjects
- Algorithms, Artificial Intelligence, Colonoscopy, Humans, Colonic Polyps diagnosis, Colonic Polyps pathology, Colorectal Neoplasms diagnosis, Colorectal Neoplasms pathology
- Abstract
Objectives: There is uncertainty regarding the efficacy of artificial intelligence (AI) software to detect advanced subtle neoplasia, particularly flat lesions and sessile serrated lesions (SSLs), due to low prevalence in testing datasets and prospective trials. This has been highlighted as a top research priority for the field., Methods: An AI algorithm was evaluated on four video test datasets containing 173 polyps (35,114 polyp-positive frames and 634,988 polyp-negative frames) specifically enriched with flat lesions and SSLs, including a challenging dataset containing subtle advanced neoplasia. The challenging dataset was also evaluated by eight endoscopists (four independent, four trainees, according to the Joint Advisory Group on gastrointestinal endoscopy [JAG] standards in the UK)., Results: In the first two video datasets, the algorithm achieved per-polyp sensitivities of 100% and 98.9%. Per-frame sensitivities were 84.1% and 85.2%. In the subtle dataset, the algorithm detected a significantly higher number of polyps (P < 0.0001), compared to JAG-independent and trainee endoscopists, achieving per-polyp sensitivities of 79.5%, 37.2% and 11.5%, respectively. Furthermore, when considering subtle polyps detected by both the algorithm and at least one endoscopist, the AI detected polyps significantly faster on average., Conclusions: The AI based algorithm achieved high per-polyp sensitivities for advanced colorectal neoplasia, including flat lesions and SSLs, outperforming both JAG independent and trainees on a very challenging dataset containing subtle lesions that could have been overlooked easily and contribute to interval colorectal cancer. Further prospective trials should evaluate AI to detect subtle advanced neoplasia in higher risk populations for colorectal cancer., (© 2021 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)
- Published
- 2022
- Full Text
- View/download PDF
49. A comparison of epithelial cell content of oral samples estimated using cytology and DNA methylation.
- Author
-
Wong YT, Tayeb MA, Stone TC, Lovat LB, Teschendorff AE, Iwasiow R, and Craig JM
- Subjects
- Adult, Child, CpG Islands, Epigenesis, Genetic, Epithelial Cells metabolism, Genome-Wide Association Study, Humans, Leukocytes metabolism, DNA Methylation, Epigenomics methods
- Abstract
Saliva and buccal samples are popular for epigenome wide association studies (EWAS) due to their ease of collection compared and their ability to sample a different cell lineage compared to blood. As these samples contain a mix of white blood cells and buccal epithelial cells that can vary within a population, this cellular heterogeneity may confound EWAS. This has been addressed by including cellular heterogeneity obtained through cytology at the time of collection or by using cellular deconvolution algorithms built on epigenetic data from specific cell types. However, to our knowledge, the two methods have not yet been compared. Here we show that the two methods are highly correlated in saliva and buccal samples (R = 0.84, P < 0.0001) by comparing data generated from cytological staining and Infinium MethylationEPIC arrays and the EpiDISH deconvolution algorithm from buccal and saliva samples collected from twenty adults. In addition, by using an expanded dataset from both sample types, we confirmed our previous finding that age has strong, non-linear negative correlation with epithelial cell proportion in both sample types. However, children and adults showed a large within-population variation in cellular heterogeneity. Our results validate the use of the EpiDISH algorithm in estimating the effect of cellular heterogeneity in EWAS and showed DNA methylation generally underestimates the epithelial cell content obtained from cytology.
- Published
- 2022
- Full Text
- View/download PDF
50. Novel epigenetic network biomarkers for early detection of esophageal cancer.
- Author
-
Maity AK, Stone TC, Ward V, Webster AP, Yang Z, Hogan A, McBain H, Duku M, Ho KMA, Wolfson P, Graham DG, Beck S, Teschendorff AE, and Lovat LB
- Subjects
- Biomarkers, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, DNA Methylation, Disease Progression, Early Detection of Cancer, Epigenesis, Genetic, Epigenomics, Humans, Barrett Esophagus diagnosis, Barrett Esophagus genetics, Esophageal Neoplasms diagnosis, Esophageal Neoplasms genetics, Esophageal Neoplasms pathology
- Abstract
Background: Early detection of esophageal cancer is critical to improve survival. Whilst studies have identified biomarkers, their interpretation and validity is often confounded by cell-type heterogeneity., Results: Here we applied systems-epigenomic and cell-type deconvolution algorithms to a discovery set encompassing RNA-Seq and DNA methylation data from esophageal adenocarcinoma (EAC) patients and matched normal-adjacent tissue, in order to identify robust biomarkers, free from the confounding effect posed by cell-type heterogeneity. We identify 12 gene-modules that are epigenetically deregulated in EAC, and are able to validate all 12 modules in 4 independent EAC cohorts. We demonstrate that the epigenetic deregulation is present in the epithelial compartment of EAC-tissue. Using single-cell RNA-Seq data we show that one of these modules, a proto-cadherin module centered around CTNND2, is inactivated in Barrett's Esophagus, a precursor lesion to EAC. By measuring DNA methylation in saliva from EAC cases and controls, we identify a chemokine module centered around CCL20, whose methylation patterns in saliva correlate with EAC status., Conclusions: Given our observations that a CCL20 chemokine network is overactivated in EAC tissue and saliva from EAC patients, and that in independent studies CCL20 has been found to be overactivated in EAC tissue infected with the bacterium F. nucleatum, a bacterium that normally inhabits the oral cavity, our results highlight the possibility of using DNAm measurements in saliva as a proxy for changes occurring in the esophageal epithelium. Both the CTNND2/CCL20 modules represent novel promising network biomarkers for EAC that merit further investigation., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.