Imperial College London

MrChristopherPeters

Faculty of MedicineDepartment of Surgery & Cancer

Clinical Senior Lecturer in Upper GI
 
 
 
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Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Publication Type
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90 results found

Nazarian S, Gkouzionis I, Murphy J, Darzi A, Patel N, Peters CJ, Elson DSet al., 2024, Real-time classification of tumour and non-tumour tissue in colorectal cancer using diffuse reflectance spectroscopy and neural networks to aid margin assessment, International Journal of Surgery, ISSN: 1743-9159

Background: Colorectal cancer is the third most commonly diagnosed malignancy and the second leading cause of mortality worldwide. A positive resection margin following surgery for colorectal cancer is linked with higher rates of local recurrence and poorer survival. We investigated diffuse reflectance spectroscopy (DRS) to distinguish tumour and non-tumour tissue in ex vivo colorectal specimens, to aid margin assessment and provide augmented visual maps to the surgeon in real-time.Methods: Patients undergoing elective colorectal cancer resection surgery at a London-based hospital were prospectively recruited. A hand-held DRS probe was used on the surface of freshly resected ex vivo colorectal tissue. Spectral data was acquired for tumour and non-tumour tissue. Binary classification was achieved using conventional machine learning classifiers and a convolutional neural network (CNN), which were evaluated in terms of sensitivity, specificity, accuracy and the area under the curve.Results: A total of 7692 mean spectra were obtained for tumour and non-tumour colorectal tissue. The CNN-based classifier was the best performing machine learning algorithm, when compared to contrastive approaches, for differentiating tumour and non-tumour colorectal tissue, with an overall diagnostic accuracy of 90.8% and area under the curve of 96.8%. Live on-screen classification of tissue type was achieved using a graduated colourmap.Conclusion: A high diagnostic accuracy for a DRS probe and tracking system to differentiate ex vivo tumour and non-tumour colorectal tissue in real-time with on-screen visual feedback was highlighted by this study. Further in vivo studies are needed to ensure integration into a surgical workflow.

Journal article

Peters CJ, Ang Y, Ciccarelli FD, Coles H, Coleman HG, Contino G, Crosby T, Devonshire G, Eldridge M, Freeman A, Grehan N, McCord M, Nutzinger B, Zamani S, Parsons SL, Petty R, Sharrocks AD, Skipworth RJE, Smyth EC, Soomro I, Underwood TJ, OCCAMS Consortium, Fitzgerald RCet al., 2024, A decade of the Oesophageal Cancer Clinical and Molecular Stratification Consortium, Nature Medicine, Vol: 30, Pages: 14-16, ISSN: 1078-8956

Journal article

Savva K-V, Kawka M, Vadhwana B, Penumaka R, Patton I, Khan K, Perrott C, Das S, Giot M, Mavroveli S, Hanna GB, Ni MZ, Peters CJet al., 2023, The Biomarker Toolkit - an evidence-based guideline to predict cancer biomarker success and guide development, BMC Medicine, Vol: 21, ISSN: 1741-7015

BACKGROUND: An increased number of resources are allocated on cancer biomarker discovery, but very few of these biomarkers are clinically adopted. To bridge the gap between Biomarker discovery and clinical use, we aim to generate the Biomarker Toolkit, a tool designed to identify clinically promising biomarkers and promote successful biomarker translation. METHODS: All features associated with a clinically useful biomarker were identified using mixed-methodology, including systematic literature search, semi-structured interviews, and an online two-stage Delphi-Survey. Validation of the checklist was achieved by independent systematic literature searches using keywords/subheadings related to clinically and non-clinically utilised breast and colorectal cancer biomarkers. Composite aggregated scores were generated for each selected publication based on the presence/absence of an attribute listed in the Biomarker Toolkit checklist. RESULTS: Systematic literature search identified 129 attributes associated with a clinically useful biomarker. These were grouped in four main categories including: rationale, clinical utility, analytical validity, and clinical validity. This checklist was subsequently developed using semi-structured interviews with biomarker experts (n=34); and 88.23% agreement was achieved regarding the identified attributes, via the Delphi survey (consensus level:75%, n=51). Quantitative validation was completed using clinically and non-clinically implemented breast and colorectal cancer biomarkers. Cox-regression analysis suggested that total score is a significant driver of biomarker success in both cancer types (BC: p>0.0001, 95.0% CI: 0.869-0.935, CRC: p>0.0001, 95.0% CI: 0.918-0.954). CONCLUSIONS: This novel study generated a validated checklist with literature-reported attributes linked with successful biomarker implementation. Ultimately, the application of this toolkit can be used to detect biomarkers with the highest clinical

Journal article

Brown MRD, Knight M, Peters CJ, Maleki S, Motavalli A, Nedjat-Shokouhi Bet al., 2023, Digital outpatient health solutions as a vehicle to improve healthcare sustainability-a United Kingdom focused policy and practice perspective, Frontiers in Digital Health, Vol: 5, ISSN: 2673-253X

Introduction: In the midst of a global climate emergency and with health care systems across the world facing extreme pressure, interest in digital approaches as a potential part-solution to these challenges has increased rapidly. The evidence base to support the role that digitalization can play in moving towards more sustainable models of healthcare is growing, as is the awareness of this key area of healthcare reform amongst policy makers, clinicians and the public.Method and Results: In this policy and practice review we explore four domains of healthcare sustainability-environmental, economic, and patient and clinician, delineating the potential impact that digitally enabled healthcare can have on each area. Real-world examples are provided to illustrate the impact individual digital interventions can have on each pillar of sustainability and demonstrate the scale of the potential benefits which can be achieved.Discussion: Digitally enabled healthcare solutions present an approach which offer numerous benefits, including environmental sustainability, economic benefits, and improved patient experience. There are also potential drawbacks such as the risk of digital exclusion and the need for integration with existing technology platforms. Overall, it is essential to strike a balance between the benefits and potential drawbacks of digital healthcare solutions to ensure that they are equitable, effective, and sustainable.

Journal article

Kazachenka A, Loong JH, Attig J, Young GR, Ganguli P, Devonshire G, Grehan N, TheOCCAMS Consortium, Ciccarelli FD, Fitzgerald RC, Kassiotis Get al., 2023, The transcriptional landscape of endogenous retroelements delineates esophageal adenocarcinoma subtypes, NAR Cancer, Vol: 5, Pages: 1-20, ISSN: 2632-8674

Most cancer types exhibit aberrant transcriptional activity, including derepression of retrotransposable elements (RTEs). However, the degree, specificity and potential consequences of RTE transcriptional activation may differ substantially among cancer types and subtypes. Representing one extreme of the spectrum, we characterize the transcriptional activity of RTEs in cohorts of esophageal adenocarcinoma (EAC) and its precursor Barrett's esophagus (BE) from the OCCAMS (Oesophageal Cancer Clinical and Molecular Stratification) consortium, and from TCGA (The Cancer Genome Atlas). We found exceptionally high RTE inclusion in the EAC transcriptome, driven primarily by transcription of genes incorporating intronic or adjacent RTEs, rather than by autonomous RTE transcription. Nevertheless, numerous chimeric transcripts straddling RTEs and genes, and transcripts from stand-alone RTEs, particularly KLF5- and SOX9-controlled HERVH proviruses, were overexpressed specifically in EAC. Notably, incomplete mRNA splicing and EAC-characteristic intronic RTE inclusion was mirrored by relative loss of the respective fully-spliced, functional mRNA isoforms, consistent with compromised cellular fitness. Defective RNA splicing was linked with strong transcriptional activation of a HERVH provirus on Chr Xp22.32 and defined EAC subtypes with distinct molecular features and prognosis. Our study defines distinguishable RTE transcriptional profiles of EAC, reflecting distinct underlying processes and prognosis, thus providing a framework for targeted studies.

Journal article

Abbas S, Pich OA, Devonshire G, Zamani S, Katz-Summercorn A, Killcoyne S, Cheah C, Nutzinger B, Grehan N, Lopez-Bigas N, Edwards PAW, Fidziukiewicz EM, Redmond A, Freeman AC, Smyth E, O'Donovan M, Miremadi A, Malhotra S, Tripathi M, Coles H, Flint C, Eldridge M, Jammula S, Davies J, Crichton C, Carroll NH, Hardwick R, Safranek P, Hindmarsh A, Sujendran VJ, Hayes S, Ang Y, Sharrocks AR, Preston S, Bagwan I, Save V, Skipworth RJER, Hupp T, O'Neill JR, Tucker O, Beggs A, Taniere P, Puig S, Contino GJ, Underwood TC, Walker RL, Grace B, Lagergren J, Gossage J, Davies A, Chang F, Mahadeva U, Goh VD, Ciccarelli F, Sanders G, Berrisford R, Chan D, Cheong E, Kumar B, Sreedharan LL, Parsons S, Soomro I, Kaye P, Saunders J, Lovat L, Haidry R, Scott M, Sothi S, Lishman SB, Hanna GJ, Peters C, Moorthy K, Grabowska A, Turkington R, McManus D, Coleman HD, Petty R, Bartlett FC, Fitzgerald R, Secrier Met al., 2023, Mutational signature dynamics shaping the evolution of oesophageal adenocarcinoma, NATURE COMMUNICATIONS, Vol: 14

Journal article

Gkouzionis I, Zhong Y, Nazarian S, Darzi A, Patel N, Peters CJ, Elson DSet al., 2023, A YOLOv5-based network for the detection of a diffuse reflectance spectroscopy probe to aid surgical guidance in gastrointestinal cancer surgery, International Journal of Computer Assisted Radiology and Surgery, Vol: 19, ISSN: 1861-6410

PURPOSE: A positive circumferential resection margin (CRM) for oesophageal and gastric carcinoma is associated with local recurrence and poorer long-term survival. Diffuse reflectance spectroscopy (DRS) is a non-invasive technology able to distinguish tissue type based on spectral data. The aim of this study was to develop a deep learning-based method for DRS probe detection and tracking to aid classification of tumour and non-tumour gastrointestinal (GI) tissue in real time. METHODS: Data collected from both ex vivo human tissue specimen and sold tissue phantoms were used for the training and retrospective validation of the developed neural network framework. Specifically, a neural network based on the You Only Look Once (YOLO) v5 network was developed to accurately detect and track the tip of the DRS probe on video data acquired during an ex vivo clinical study. RESULTS: Different metrics were used to analyse the performance of the proposed probe detection and tracking framework, such as precision, recall, mAP 0.5, and Euclidean distance. Overall, the developed framework achieved a 93% precision at 23 FPS for probe detection, while the average Euclidean distance error was 4.90 pixels. CONCLUSION: The use of a deep learning approach for markerless DRS probe detection and tracking system could pave the way for real-time classification of GI tissue to aid margin assessment in cancer resection surgery and has potential to be applied in routine surgical practice.

Journal article

Booth ME, Jones CM, Helbrow J, Mansoor W, Peters CJ, Petty RD, Underwood TJ, Smyth EC, Crosby Tet al., 2023, The UK National Oesophagogastric Multidisciplinary Team Meeting: an initiative from the UK & Ireland Oesophagogastric Group, Clinical Oncology, ISSN: 0936-6555

Journal article

Nazarian S, Gkouzionis I, Peters CJ, 2023, Using diffuse reflectance spectroscopy to classify tumor tissue in upper gastrointestinal cancers - reply, JAMA Surgery, Vol: 158, ISSN: 2168-6262

Journal article

Moorthy K, Halliday LJ, Noor N, Peters CJ, Wynter-Blyth V, Urch CEet al., 2023, Feasibility of implementation and the impact of a digital prehabilitation service in patients undergoing treatment for oesophago-gastric cancer, Current Oncology, Vol: 30, Pages: 1673-1682, ISSN: 1198-0052

Background: Home-based and supervised prehabilitation programmes are shown to have a positive impact on outcomes in patients with oesophago-gastric (OG) cancer. The primary aim of this study was to establish the feasibility of delivering a digital prehabilitation service. Methods: Patients undergoing treatment for OG cancer with curative intent were recruited into the study. During the COVID-19 pandemic, patients were offered a digital prehabilitation service. Following the lifting of COVID-19 restrictions, patients were also offered both a hybrid clinic-based in-person service and a digital service. Implementation and clinical metrics from the two prehabilitation models were compared. Results: 31 of 41 patients accepted the digital service (75%). Of the people who started the digital programme, 3 dropped out (10%). Compliance with the weekly touchpoints was 86%, and the median length of programme was 12 weeks. Twenty-six patients enrolled in the in-person service. Two patients dropped out (10%). Average compliance to weekly touchpoints was 71%, and the median length of programme was 10 weeks. In the digital group, sit to stand (STS) increased from 14.5 (IQR 10.5–15.5) to 16 (IQR 16–22); p = 0.02. Median heart rate recovery (HRR) increased from 10.5 (IQR 7.5–14) to 15.5 (IQR 11–20) bpm; p = 0.24. There was a significant drop in distress (median 3 (IQR 0–5) to 1 (IQR 0–2); p = 0.04) and a small drop in anxiety (median 3 (0–5) to 2 (0–3); p = 0.22). There was no difference in the postoperative complication rate and length of hospital stay between the two groups. Discussion: This study has shown that digital prehabilitation can be delivered effectively to patients with OG cancer, with high engagement and retention rates. We observed improvements in some physical and psychological parameters with the digital service, with comparable clinical outcomes to the in-person service.

Journal article

Gkouzionis I, Nazarian S, Patel N, Darzi A, Peters C, Elson Det al., 2023, Diffuse reflectance spectroscopy for in-vivo stomach and oesophageal tissue classification during upper gastrointestinal cancer surgery, Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XXI

Conference paper

Nazarian S, Gkouzionis I, Darzi A, Patel N, Elson D, Peters Cet al., 2023, Real-time Classification of Tumour and Non-tumour Colorectal Tissue using Diffuse Reflectance Spectroscopy to Aid Resection Margin Assessment, Digestive Diseases Week

Conference paper

Peters CJ, Bonanomi G, Fehervari M, Lairy A, Fakih-Gomez N, Alyaqout K, Efthimiou Eet al., 2023, Management of Bariatric Emergencies by the General Surgeon, Obesity, Bariatric and Metabolic Surgery: A Comprehensive Guide: Second Edition, Pages: 1323-1339, ISBN: 9783030605957

The epidemic of obesity affects almost all countries of the developed world and has led to a dramatic increase in the number of bariatric procedures worldwide. In the UK, the adoption of weight loss surgery has been via dedicated regional bariatric centers, and there is a drive for shorter stays in hospital after surgery. Both these factors make it inevitable that almost every doctor, sooner or later, will encounter a patient who has undergone bariatric surgery, even if they do not work in a bariatric center. Although safe, bariatric surgery has potential complications, which if recognized early and treated promptly can minimize the negative impact on outcomes. It is important that the non-bariatric general surgeon has at least a working knowledge of bariatric procedures and the complications that can arise. They need to remain vigilant and understand the necessity for early intervention. The basic principles of management must always include early discussion with a bariatric center and transfer, if possible. Bariatric patients often have high anesthetic risks and low reserves; therefore, deterioration can be rapid and interventions fraught with difficulties. This chapter aims to assist doctors and healthcare professionals who wish to increase their awareness and confidence in dealing with bariatric emergencies. It also provides them with some advice on what to do when they face such patients. It will cover the important complications for the major bariatric procedures, namely, gastric band, gastric bypass, sleeve gastrectomy, and intragastric balloon.

Book chapter

Gkouzionis I, Nazarian S, Darzi A, Patel N, Peters C, Elson Det al., 2023, Diffuse reflectance spectroscopy for tissue discrimination during in vivo upper gastrointestinal cancer surgery, European Conferences on Biomedical Opticsfd

Conference paper

Baggaley AE, Lafaurie GBRC, Tate SJ, Boshier PR, Case A, Prosser S, Torkington J, Jones SEF, Gwynne SH, Peters CJet al., 2023, Pressurized intraperitoneal aerosol chemotherapy (PIPAC): updated systematic review using the IDEAL framework, British Journal of Surgery, Vol: 110, Pages: 10-18, ISSN: 0007-1323

Journal article

Savva K-V, Das B, Antonowicz S, Hanna GB, Peters CJet al., 2022, Progress with metabolomic blood tests for gastrointestinal cancer diagnosis-an assessment of biomarker translation, Cancer Epidemiology, Biomarkers and Prevention, Vol: 31, Pages: 2095-2105, ISSN: 1055-9965

There is an urgent need for cost-effective, non-invasive tools to detect early stages of gastrointestinal cancer (colorectal, gastric, and esophageal cancers). Despite many publications suggesting circulating metabolites acting as accurate cancer biomarkers, few have reached the clinic. In upper gastrointestinal cancer this is critically important, as there is no test to complement gold-standard endoscopic evaluation in patients with mild symptoms that do not meet referral criteria. Therefore, this study aimed to describe and solve this translational gap. Studies reporting diagnostic accuracy of metabolomic blood-based gastrointestinal cancer biomarkers from 2007 to 2020 were systematically reviewed and progress of each biomarker along the discovery–validation–adoption pathway was mapped. Successful biomarker translation was defined as a composite endpoint, including patent protection/FDA approval/recommendation in national guidelines. The review found 77 biomarker panels of gastrointestinal cancer, including 25 with an AUROC >0.9. All but one was stalled at the discovery phase, 9.09% were patented and none were clinically approved, confirming the extent of biomarker translational gap. In addition, there were numerous “re-discoveries,” including histidine, discovered in 7 colorectal studies. Finally, this study quantitatively supports the presence of a translational gap between discovery and clinical adoption, despite clear evidence of highly performing biomarkers with significant potential clinical value.

Journal article

Case A, Prosser S, Peters CJ, Adams R, Gwynne S, PIPAC UK Collaborativeet al., 2022, Pressurised intraperitoneal aerosolised chemotherapy (PIPAC) for gastric cancer with peritoneal metastases: a systematic review by the PIPAC UK collaborative, Critical Reviews in Oncology Hematology, Vol: 180, Pages: 1-16, ISSN: 1040-8428

INTRODUCTION: Gastric cancer with peritoneal metastases (GCPM) carries a poor prognosis. Pressurised Intraperitoneal Aerosolised Chemotherapy (PIPAC) offers pharmacokinetic advantages over intravenous therapy, resulting in higher chemotherapy concentrations in peritoneal deposits, and potentially reduced systemic absorption/toxicity. This review evaluates efficacy, tolerability and impact on quality of life (QOL) of PIPAC for GCPM. METHODS: Following registration with PROSPERO (CRD42021281500), MEDLINE, EMBASE and The Cochrane Library were searched for PIPAC in patients with peritoneal metastases, in accordance with PRISMA standards RESULTS: Across 18 included reports representing 751 patients with GCPM (4 prospective, 11 retrospective, 3 abstracts, no phase III studies), median overall survival (mOS) was 8 - 19.1 months, 1-year OS 49.8-77.9%, complete response (PRGS1) 0-35% and partial response (PRGS2/3) 0-83.3%. Grade 3 and 4 toxicity was 0.7-25% and 0-4.1% respectively. Three studies assessing QOL reported no significant difference. CONCLUSION: PIPAC may offer promising survival benefits, toxicity, and QOL for GCPM.

Journal article

Nazarian S, Gkouzionis I, Kawka M, Jamroziak M, Lloyd J, Darzi A, Patel N, Elson DS, Peters CJet al., 2022, Real-time tracking and classification of tumour and non-tumour tissue in upper gastrointestinal cancers using diffuse reflectance spectroscopy for resection margin assessment, JAMA Surgery, ISSN: 2168-6254

Importance:Cancers of the upper gastrointestinal tract remain a major contributor to the global cancer burden. The accurate mapping of tumour margins is of particular importance for curative cancer resection and improvement in overall survival. Current mapping techniques preclude a full resection margin assessment in real-time.Objective:We aimed to use diffuse reflectance spectroscopy on gastric and oesophageal cancer specimens to differentiate tissue types and provide real-time feedback to the operator.Design:This was a prospective ex vivo validation study. Patients undergoing oesophageal or gastric cancer resection were prospectively recruited into the study between July 2020 and July 2021 at Hammersmith Hospital in London, United Kingdom.Setting:This was a single-centre study based at a tertiary hospital.Participants:Tissue specimens were included for patients undergoing elective surgery for either oesophageal carcinoma (adenocarcinoma or squamous cell carcinoma) or gastric adenocarcinoma.Exposure:A hand-held diffuse reflectance spectroscopy probe and tracking system was used on freshly resected ex vivo tissue to obtain spectral data. Binary classification, following histopathological validation, was performed using four supervised machine learning classifiers. Main Outcomes and Measures:Data were divided into training and testing sets using a stratified 5-fold cross-validation method. Machine learning classifiers were evaluated in terms of sensitivity, specificity, overall accuracy, and the area under the curve.Results:A total of 14,097 mean spectra for normal and cancerous tissue were collected from 37 patients. The machine learning classifier achieved an overall normal versus cancer diagnostic accuracy of 93.86±0.66 for stomach tissue and 96.22±0.50 for oesophageal tissue, and sensitivity and specificity of 91.31% and 95.13% for stomach and 94.60% and 97.28% for oesophagus, respectively. Real-time tissue tracking and classification was achieved a

Journal article

Elson D, Nazarian S, Gkouzionis I, Patel N, Darzi A, Peters Cet al., 2022, Real-time Classification of Colorectal Tissue Using Diffuse Reflectance Spectroscopy to Aid Margin Assessment, European Society of Coloproctology Scientific Conference

Conference paper

Salem V, Hirani D, Lloyd C, Regan L, Peters Cet al., 2022, Why are women still leaving academic medicine? A qualitative study within a London Medical School, BMJ Open, Vol: 12, ISSN: 2044-6055

Objectives: To identify factors that influenced women who chose to leave academic medicine.Design and main outcome measures: Independent consultants led a focus group of women in medicine who had left academia after completion of their postgraduate research degree at Imperial College London Faculty of Medicine. Thematic analysis was performed on the transcribed conversations.Participants and setting: Nine women physicians who completed a postgraduate degree (MD or PhD) at a large London Medical School and Academic Health Sciences Centre, Imperial College London, but did not go on to pursue a career in academic medicine.Results: Influences to leave clinical academia were summarised under eight themes—career intentions, supervisor support, institutional human resources support, inclusivity, work–life balance, expectations, mentors and role models, and pregnancy and maternity leave.Conclusion: The women in our focus group reported several factors contributing to their decision to leave clinical academia, which included lack of mentoring tailored to specific needs, low levels of acceptance for flexible working to help meet parental responsibilities and perceived explicit gender biases. We summarise the multiple targeted strategies that Imperial College London has implemented to promote retention of women in academic medicine, although more research needs to be done to ascertain the most effective interventions.

Journal article

Boshier PR, Swaray A, Vadhwana B, O'Sullivan A, Low DE, Hanna GB, Peters CJ, POEM Biomarkers Consortium and OCCAMS Consortiumet al., 2022, Systematic review and validation of clinical models predicting survival after oesophagectomy for adenocarcinoma, British Journal of Surgery, Vol: 109, Pages: 418-425, ISSN: 0007-1323

BACKGROUND: Oesophageal adenocarcinoma poses a significant global health burden, yet the staging used to predict survival has limited ability to stratify patients by outcome. This study aimed to identify published clinical models that predict survival in oesophageal adenocarcinoma and to evaluate them using an independent international multicentre dataset. METHODS: A systematic literature search (title and abstract) using the Ovid Embase and MEDLINE databases (from 1947 to 11 July 2020) was performed. Inclusion criteria were studies that developed or validated a clinical prognostication model to predict either overall or disease-specific survival in patients with oesophageal adenocarcinoma undergoing surgical treatment with curative intent. Published models were validated using an independent dataset of 2450 patients who underwent oesophagectomy for oesophageal adenocarcinoma with curative intent. RESULTS: Seventeen articles were eligible for inclusion in the study. Eleven models were suitable for testing in the independent validation dataset and nine of these were able to stratify patients successfully into groups with significantly different survival outcomes. Area under the receiver operating characteristic curves for individual survival prediction models ranged from 0.658 to 0.705, suggesting poor-to-fair accuracy. CONCLUSION: This study highlights the need to concentrate on robust methodologies and improved, independent, validation, to increase the likelihood of clinical adoption of survival predictions models.

Journal article

Ng AWT, Contino G, Killcoyne S, Devonshire G, Hsu R, Abbas S, Su J, Redmond AM, Weaver JMJ, Eldridge MD, Tavaré S, Oesophageal Cancer Clinical and Molecular Stratification OCCAMS Consortium, Edwards PAW, Fitzgerald RCet al., 2022, Rearrangement processes and structural variations show evidence of selection in oesophageal adenocarcinomas, Communications Biology, Vol: 5, ISSN: 2399-3642

Oesophageal adenocarcinoma (OAC) provides an ideal case study to characterize large-scale rearrangements. Using whole genome short-read sequencing of 383 cases, for which 214 had matched whole transcriptomes, we observed structural variations (SV) with a predominance of deletions, tandem duplications and inter-chromosome junctions that could be identified as LINE-1 mobile element (ME) insertions. Complex clusters of rearrangements resembling breakage-fusion-bridge cycles or extrachromosomal circular DNA accounted for 22% of complex SVs affecting known oncogenes. Counting SV events affecting known driver genes substantially increased the recurrence rates of these drivers. After excluding fragile sites, we identified 51 candidate new drivers in genomic regions disrupted by SVs, including ETV5, KAT6B and CLTC. RUNX1 was the most recurrently altered gene (24%), with many deletions inactivating the RUNT domain but preserved the reading frame, suggesting an altered protein product. These findings underscore the importance of identification of SV events in OAC with implications for targeted therapies.

Journal article

Sivakumar J, Forshaw MJ, Lam S, Peters CJ, Allum WH, Whibley J, Sinclair RCF, Snowden CP, Hii MW, Sivakumar H, Read Met al., 2022, Identifying the limitations of cardiopulmonary exercise testing prior to esophagectomy using a pooled analysis of patient-level data, Diseases of the Esophagus, Vol: 35, Pages: 1-10, ISSN: 1120-8694

Preoperative cardiopulmonary exercise testing (CPET) provides an objective assessment of aerobic fitness in patients undergoing surgery. While peak oxygen uptake during exercise (VO2peak) and anaerobic threshold have demonstrated a moderate correlation with the development of complications following esophagectomy, no clinically useful threshold values have been defined. By pooling patient level data from existing studies, we aimed to define optimal thresholds for preoperative CPET parameters to predict patients at high risk of postoperative complications. Studies reporting on the relationship between preoperative CPET variables and post-esophagectomy complications were determined from a comprehensive literature search. Patient-level data were obtained from six contributing centers for pooled-analyses. Outcomes of interest included cardiopulmonary and non-cardiopulmonary complications, unplanned intensive care unit readmission, and 90-day and 12-month all-cause mortality. Receiver operating characteristic curves and logistic regression models estimated the predictive value of CPET parameters for each individual outcome of interest. This analysis comprised of 621 patients who underwent CPET prior to esophagectomy during the period from January 2004 to March 2017. For both anaerobic threshold and VO2peak, none of the receiver operating characteristic curves achieved an area under the curve value > 0.66 for the outcomes of interest. The discriminatory ability of CPET for determining high-risk patients was found to be poor in patients undergoing an esophagectomy. CPET may only carry an adjunct role to clinical decision-making.

Journal article

Gkouzionis I, Nazarian S, Kawka M, Darzi A, Patel N, Peters C, Elson Det al., 2022, Real-time tracking of a diffuse reflectance spectroscopy probe used to aid histological validation of margin assessment in upper gastrointestinal cancer resection surgery, Journal of Biomedical Optics, Vol: 27, ISSN: 1083-3668

Significance: Diffuse reflectance spectroscopy (DRS) allows discrimination of tissue type. Its application is limited by the inability to mark the scanned tissue and the lack of real-time measurements.Aim: This study aimed to develop a real-time tracking system to enable localization of a DRS probe to aid the classification of tumor and non-tumor tissue.Approach: A green-colored marker attached to the DRS probe was detected using hue-saturation-value (HSV) segmentation. A live, augmented view of tracked optical biopsy sites was recorded in real time. Supervised classifiers were evaluated in terms of sensitivity, specificity, and overall accuracy. A developed software was used for data collection, processing, and statistical analysis.Results: The measured root mean square error (RMSE) of DRS probe tip tracking was 1.18  ±  0.58  mm and 1.05  ±  0.28  mm for the x and y dimensions, respectively. The diagnostic accuracy of the system to classify tumor and non-tumor tissue in real time was 94% for stomach and 96% for the esophagus.Conclusions: We have successfully developed a real-time tracking and classification system for a DRS probe. When used on stomach and esophageal tissue for tumor detection, the accuracy derived demonstrates the strength and clinical value of the technique to aid margin assessment in cancer resection surgery.

Journal article

Elson D, Gkouzionis I, Nazarian S, Darzi A, Patel N, Peters Cet al., 2022, Real-time tracking of a diffuse reflectance spectroscopy probe for tissue classification in colorectal cancer surgery, Hamlyn Symposium on Medical Robotics Workshop on Sensing and biophotonics for surgical robotics and in vivo diagnostics

Conference paper

Gkouzionis I, Nazarian S, Darzi A, Patel N, Elson D, Peters Cet al., 2022, Discriminating between cancer and healthy tissue in upper gastrointestinal cancer surgery using deep learning and diffuse reflectance spectroscopy, London Surgery Symposium

Conference paper

Gkouzionis I, Nazarian S, Kawka M, Darzi A, Patel N, Peters C, Elson Det al., 2022, Real-time tissue classification in stomach and oesophageal cancer based on optical tracking of a diffuse reflectance spectroscopy probe, Photonics West: Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XX

Conference paper

Gkouzionis I, Nazarian S, Darzi A, Patel N, Peters C, Elson Det al., 2022, Three-dimensional tissue reconstruction and tracking of a diffuse reflectance spectroscopy probe for real-time tissue classification in upper gastrointestinal cancer surgery, Photonics Europe: Clinical Biophotonics II

Conference paper

Gkouzionis I, Nazarian S, Patel N, Peters C, Elson DSet al., 2022, Towards real-time upper gastrointestinal resection margin assessment using a diffuse reflectance spectroscopy probe

The use of a diffuse reflectance spectroscopy probe for real-time classification of stomach and oesophageal tissue specimen can aid resection margin assessment in upper gastrointestinal cancer surgery.

Conference paper

Elson D, Gkouzionis I, Nazarian S, Darzi A, Patel N, Peters Cet al., 2022, Using diffuse reflectance spectroscopy for real-time tissue assessment during upper gastrointestinal cancer surgery, IEEE International Conference on Biomedical and Health Informatics

Conference paper

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