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

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52 results found

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

Baggaley AE, Lafaurie GBRC, Tate SJ, Boshier PR, Case A, Prosser S, Torkington J, Jones SEF, Gwynne SH, Peters CJet al., 2022, Pressurized intraperitoneal aerosol chemotherapy (PIPAC): updated systematic review using the IDEAL framework, British Journal of Surgery, ISSN: 0007-1323

Journal article

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

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, ISSN: 1120-8694

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

Nazarian S, Gkouzionis I, Kawka M, Patel N, Darzi A, Elson D, Peters Cet al., 2021, Real-time tracking and classification of tumour and non-tumour tissue in upper gastrointestinal cancer specimens using diffuse reflectance spectroscopy, UGI Congress 2021, ISSN: 0007-1323

Conference paper

Gkouzionis I, Nazarian S, Anandakumar A, Darzi A, Patel N, Peters C, Elson DSet al., 2021, Using diffuse reflectance spectroscopy probe tracking to identify non-tumour and tumour tissue in upper gastrointestinal specimens, Translational Biophotonics: Diagnostics and Therapeutics, Publisher: SPIE

The use of a diffuse reflectance spectroscopy probe and tracking system was successfully used in real-time for automated tissue classification in upper gastrointestinal surgery to aid resection margin assessment.

Conference paper

Ococks E, Sharma S, Ng AWT, Aleshin A, Fitzgerald RC, Smyth Eet al., 2021, Serial Circulating Tumor DNA Detection Using a Personalized, Tumor-Informed Assay in Esophageal Adenocarcinoma Patients Following Resection., Gastroenterology, Vol: 161, Pages: 1705-1708.e2

Journal article

Savva K-V, Hage L, Belluomo I, Gummet P, Boshier PR, Peters CJet al., 2021, Assessment of the Burden of Small Intestinal Bacterial Overgrowth (SIBO) in Patients After Oesophagogastric (OG) Cancer Resection, JOURNAL OF GASTROINTESTINAL SURGERY, Vol: 26, Pages: 924-926, ISSN: 1091-255X

Journal article

Nazarian S, Gkouzionis I, Anandakumar A, Patel N, Elson D, Peters Cet al., 2021, Using diffuse reflectance spectroscopy (DRS) to identify tumour and non-tumour tissue in upper gastrointestinal specimens, Association of Surgeons of Great Britain and Ireland Virtual Congress, Publisher: British Journal of Surgery Society, Pages: 41-41, ISSN: 0007-1323

AimCancers of the upper gastrointestinal (GI) tract remain a major contributor to the global cancer risk. Surgery aims to completely resect tumour with clear margins, whilst preserving as much surrounding tissue. Diffuse reflectance spectroscopy (DRS) is a novel technique that presents a promising advancement in cancer diagnosis. We have developed a novel DRS system with tracking capability. Our aim is to classify tumour and non-tumour GI tissue in real-time using this device to aid intra-operative analysis of resection margins.MethodAn ex-vivo study was undertaken in which data was collected from consecutive patients undergoing upper GI cancer resection surgery between August 2020- January 2021. A hand-held DRS probe and tracking system was used on normal and cancerous tissue to obtain spectral information. After acquisition of all spectra, a classification system using histopathology results was created. A user interface was developed using Python 3.6 and Qt5. A support vector machine was used to classify the results.ResultsThe data included 4974 normal spectra and 2108 tumour spectra. The overall accuracy of the DRS probe in differentiating normal versus tumour tissue was 88.08% for the stomach (sensitivity 84.8%, specificity 89.3%), and 91.42% for the oesophagus (sensitivity 76.3%, specificity 98.9%).ConclusionWe have developed a successful DRS system with tracking capability, able to process thousands of spectra in a small timeframe, which can be used in real-time to distinguish tumour and non-tumour tissue. This can be used for intra-operative decision-making during upper GI cancer surgery to help select the best resection plane.

Conference paper

Antonowicz S, Bodai Z, Wiggins T, Markar SR, Boshier PR, Goh YM, Adam ME, Lu H, Kudo H, Rosini F, Goldin R, Moralli D, Green CM, Peters CJ, Habib N, Gabra H, Fitzgerald RC, Takats Z, Hanna GBet al., 2021, Endogenous aldehyde accumulation generates genotoxicity and exhaled biomarkers in esophageal adenocarcinoma, Nature Communications, Vol: 12, ISSN: 2041-1723

Volatile aldehydes are enriched in esophageal adenocarcinoma (EAC) patients’ breath and could improve early diagnosis, however the mechanisms of their production are unknown. Here, we show that weak aldehyde detoxification characterizes EAC, which is sufficient to cause endogenous aldehyde accumulation in vitro. Two aldehyde groups are significantly enriched in EAC biopsies and adjacent tissue: (i) short-chain alkanals, and (ii) medium-chain alkanals, including decanal. The short-chain alkanals form DNA-adducts, which demonstrates genotoxicity and confirms inadequate detoxification. Metformin, a putative aldehyde scavenger, reduces this toxicity. Tissue and breath concentrations of the medium-chain alkanal decanal are correlated, and increased decanal is linked to reduced ALDH3A2 expression, TP53 deletion, and adverse clinical features. Thus, we present a model for increased exhaled aldehydes based on endogenous accumulation from reduced detoxification, which also causes therapeutically actionable genotoxicity. These results support EAC early diagnosis trials using exhaled aldehyde analysis.

Journal article

Nazarian S, Gkouzionis I, Kawka M, Darzi A, Patel N, Elson D, Peters Cet al., 2021, The use of a diffuse reflectance spectroscopy probe and tracking system to classify tumour and non-tumour tissue in upper gastrointestinal cancer specimens to aid margin assessment, London Surgical Symposium

Conference paper

Gkouzionis I, Nazarian S, Kawka M, Peters C, Elson Det al., 2021, The use of machine learning for real-time detection of oesophageal and gastric cancer based on diffuse reflectance spectroscopy: a validation study, Joint Congress of the European Society for Diseases of the Esophagus and the International Gastric Cancer Association European Chapter

Conference paper

Sharma A, Khan S, Chicco M, Peters C, Oliver N, Reddy Met al., 2020, New onset diabetes presenting with DKA , spontaneous pneumomediastinum and subcutaneous emphysema: a case series, Practical Diabetes, Vol: 37, Pages: 183-187, ISSN: 2047-2897

Journal article

Knight WRC, McEwen R, Byrne BE, Habib W, Bott R, Zylstra J, Mahadeva U, Gossage JA, Fitzgerald RC, Noorani A, Edwards PAW, Grehan N, Nutzinger B, Hughes C, Fidziukiewicz E, MacRae S, Northrop A, Contino G, Li X, de la Rue R, Katz-Summercorn A, Abbas S, Loureda D, O'Donovan M, Miremadi A, Malhotra S, Tripathi M, Tavaré S, Lynch AG, Eldridge M, Secrier M, Devonshire G, Perner J, Jammula S, Davies J, Crichton C, Carroll N, Safranek P, Hindmarsh A, Sujendran V, Hayes SJ, Ang Y, Sharrocks A, Preston SR, Oakes S, Bagwan I, Save V, Skipworth RJE, Hupp TR, O'Neill JR, Tucker O, Beggs A, Taniere P, Puig S, Underwood TJ, Walker RC, Grace BL, Barr H, Shepherd N, Old O, Lagergren J, Davies A, Chang F, Goh V, Ciccarelli FD, Sanders G, Berrisford R, Harden C, Lewis M, Cheong E, Kumar B, Parsons SL, Soomro I, Kaye P, Saunders J, Lovat L, Haidry R, Igali L, Scott M, Sothi S, Suortamo S, Lishman S, Hanna GB, Moorthy K, Peters CJ, Grabowska A, Turkington R, McManus D, Coleman H, Khoo D, Fickling Wet al., 2020, Endoscopic tumour morphology impacts survival in adenocarcinoma of the oesophagus, European Journal of Surgical Oncology, ISSN: 0748-7983

BackgroundPrognostication in oesophageal cancer on the basis of preoperative variables is challenging. Many of the accepted predictors of survival are only derived after surgical treatment and may be influenced by neoadjuvant therapy. This study aims to explore the relationship between pre-treatment endoscopic tumour morphology and postoperative survival.MethodsPatients with endoscopic descriptions of tumours were identified from the prospectively managed databases including the OCCAMS database. Tumours were classified as exophytic, ulcerating or stenosing. Kaplan Meier survival analysis and multivariable Cox regression analyses were performed to determine hazard ratios (HR) with 95% confidence intervals.Results262 patients with oesophageal adenocarcinoma undergoing potentially curative resection were pooled from St Thomas’ Hospital (161) and the OCCAMS database (101). There were 70 ulcerating, 114 exophytic and 78 stenosing oesophageal adenocarcinomas. Initial tumour staging was similar across all groups (T3/4 tumours 71.4%, 70.2%, 74.4%). Median survival was 55 months, 51 months and 36 months respectively (p < 0.001). Rates of lymphovascular invasion (P = 0.0176), pathological nodal status (P = 0.0195) and pathological T stage (P = 0.0007) increased from ulcerating to exophytic to stenosing lesions. Resection margin positivity was 21.4% in ulcerating tumours compared to 54% in stenosing tumours (p < 0.001). When compared to stenosing lesions, exophytic and ulcerating lesions demonstrated a significant survival advantage on multivariable analysis (HR 0.56 95% CI 0.31–0.93, HR 0.42 95% CI 0.21–0.82).ConclusionThis study demonstrates that endoscopic morphology may be an important pre-treatment prognostic factor in oesophageal cancer. Ulcerating, exophytic and stenosing tumours may represent different pathological processes and tumour biology.

Journal article

Rahman SA, Walker RC, Lloyd MA, Grace BL, van Boxel GI, Kingma BF, Ruurda JP, van Hillegersberg R, Harris S, Parsons S, Mercer S, Griffiths EA, O'Neill JR, Turkington R, Fitzgerald RC, Underwood TJ, OCCAMS Consortiumet al., 2020, Machine learning to predict early recurrence after oesophageal cancer surgery., Br J Surg, Vol: 107, Pages: 1042-1052

BACKGROUND: Early cancer recurrence after oesophagectomy is a common problem, with an incidence of 20-30 per cent despite the widespread use of neoadjuvant treatment. Quantification of this risk is difficult and existing models perform poorly. This study aimed to develop a predictive model for early recurrence after surgery for oesophageal adenocarcinoma using a large multinational cohort and machine learning approaches. METHODS: Consecutive patients who underwent oesophagectomy for adenocarcinoma and had neoadjuvant treatment in one Dutch and six UK oesophagogastric units were analysed. Using clinical characteristics and postoperative histopathology, models were generated using elastic net regression (ELR) and the machine learning methods random forest (RF) and extreme gradient boosting (XGB). Finally, a combined (ensemble) model of these was generated. The relative importance of factors to outcome was calculated as a percentage contribution to the model. RESULTS: A total of 812 patients were included. The recurrence rate at less than 1 year was 29·1 per cent. All of the models demonstrated good discrimination. Internally validated areas under the receiver operating characteristic (ROC) curve (AUCs) were similar, with the ensemble model performing best (AUC 0·791 for ELR, 0·801 for RF, 0·804 for XGB, 0·805 for ensemble). Performance was similar when internal-external validation was used (validation across sites, AUC 0·804 for ensemble). In the final model, the most important variables were number of positive lymph nodes (25·7 per cent) and lymphovascular invasion (16·9 per cent). CONCLUSION: The model derived using machine learning approaches and an international data set provided excellent performance in quantifying the risk of early recurrence after surgery, and will be useful in prognostication for clinicians and patients.

Journal article

Jammula S, Katz-Summercorn AC, Li X, Linossi C, Smyth E, Killcoyne S, Biasci D, Subash VV, Abbas S, Blasko A, Devonshire G, Grantham A, Wronowski F, O'Donovan M, Grehan N, Eldridge MD, Tavaré S, Oesophageal Cancer Clinical and Molecular Stratification OCCAMS consortium, Fitzgerald RCet al., 2020, Identification of Subtypes of Barrett's Esophagus and Esophageal Adenocarcinoma Based on DNA Methylation Profiles and Integration of Transcriptome and Genome Data., Gastroenterology, Vol: 158, Pages: 1682-1697.e1

BACKGROUND & AIMS: Esophageal adenocarcinomas (EACs) are heterogeneous and often preceded by Barrett's esophagus (BE). Many genomic changes have been associated with development of BE and EAC, but little is known about epigenetic alterations. We performed epigenetic analyses of BE and EAC tissues and combined these data with transcriptome and genomic data to identify mechanisms that control gene expression and genome integrity. METHODS: In a retrospective cohort study, we collected tissue samples and clinical data from 150 BE and 285 EAC cases from the Oesophageal Cancer Classification and Molecular Stratification consortium in the United Kingdom. We analyzed methylation profiles of all BE and EAC tissues and assigned them to subgroups using non-negative matrix factorization with k-means clustering. Data from whole-genome sequencing and transcriptome studies were then incorporated; we performed integrative methylation and RNA-sequencing analyses to identify genes that were suppressed with increased methylation in promoter regions. Levels of different immune cell types were computed using single-sample gene set enrichment methods. We derived 8 organoids from 8 EAC tissues and tested their sensitivity to different drugs. RESULTS: BE and EAC samples shared genome-wide methylation features, compared with normal tissues (esophageal, gastric, and duodenum; controls) from the same patients and grouped into 4 subtypes. Subtype 1 was characterized by DNA hypermethylation with a high mutation burden and multiple mutations in genes in cell cycle and receptor tyrosine signaling pathways. Subtype 2 was characterized by a gene expression pattern associated with metabolic processes (ATP synthesis and fatty acid oxidation) and lack methylation at specific binding sites for transcription factors; 83% of samples of this subtype were BE and 17% were EAC. The third subtype did not have changes in methylation pattern, compared with control tissue, but had a gene expression pattern t

Journal article

Gkouzionis IA, Avila-Rencoret F, Peters C, Elson Det al., 2020, Hyperspectral circumferential resection margin assessment for gastrointestinal cancer surgery, Biophotonics and Imaging Graduate Summer School 2020

Conference paper

Bornschein J, Wernisch L, Secrier M, Miremadi A, Perner J, MacRae S, O'Donovan M, Newton R, Menon S, Bower L, Eldridge MD, Devonshire G, Cheah C, Turkington R, Hardwick RH, Selgrad M, Venerito M, Malfertheiner P, Fitzgerald RC, Noorani A, Elliott RF, Edwards PAW, Grehan N, Nutzinger B, Crawte J, Chettouh H, Contino G, Li X, Gregson E, Zeki S, de la Rue R, Malhotra S, Tavare S, Lynch AG, Smith ML, Davies J, Crichton C, Carroll N, Safranek P, Hindmarsh A, Sujendran V, Hayes SJ, Ang Y, Preston SR, Oakes S, Bagwan I, Save V, Skipworth RJE, Hupp TR, O'Neill JR, Tucker O, Beggs A, Taniere P, Puig S, Underwood TJ, Noble F, Owsley J, Barr H, Shepherd N, Old O, Lagergren J, Gossage J, Davies A, Chang F, Zylstra J, Goh V, Ciccarelli FD, Sanders G, Berrisford R, Harden C, Bunting D, Lewis M, Cheong E, Kumar B, Parsons SL, Soomro I, Kaye P, Saunders J, Lovat L, Haidry R, Eneh V, Igali L, Scott M, Sothi S, Suortamo S, Lishman S, Hanna GB, Peters CJ, Grabowska Aet al., 2019, Transcriptomic profiling reveals three molecular phenotypes of adenocarcinoma at the gastroesophageal junction, International Journal of Cancer, Vol: 145, Pages: 3389-3401, ISSN: 0020-7136

Cancers occurring at the gastroesophageal junction (GEJ) are classified as predominantly esophageal or gastric, which is often difficult to decipher. We hypothesized that the transcriptomic profile might reveal molecular subgroups which could help to define the tumor origin and behavior beyond anatomical location. The gene expression profiles of 107 treatment‐naïve, intestinal type, gastroesophageal adenocarcinomas were assessed by the Illumina‐HTv4.0 beadchip. Differential gene expression (limma), unsupervised subgroup assignment (mclust) and pathway analysis (gage) were undertaken in R statistical computing and results were related to demographic and clinical parameters. Unsupervised assignment of the gene expression profiles revealed three distinct molecular subgroups, which were not associated with anatomical location, tumor stage or grade (p > 0.05). Group 1 was enriched for pathways involved in cell turnover, Group 2 was enriched for metabolic processes and Group 3 for immune‐response pathways. Patients in group 1 showed the worst overall survival (p = 0.019). Key genes for the three subtypes were confirmed by immunohistochemistry. The newly defined intrinsic subtypes were analyzed in four independent datasets of gastric and esophageal adenocarcinomas with transcriptomic data available (RNAseq data: OCCAMS cohort, n = 158; gene expression arrays: Belfast, n = 63; Singapore, n = 191; Asian Cancer Research Group, n = 300). The subgroups were represented in the independent cohorts and pooled analysis confirmed the prognostic effect of the new subtypes. In conclusion, adenocarcinomas at the GEJ comprise three distinct molecular phenotypes which do not reflect anatomical location but rather inform our understanding of the key pathways expressed.

Journal article

Turkington RC, Knight LA, Blayney JK, Secrier M, Douglas R, Parkes EE, Sutton EK, Stevenson L, McManus D, Halliday S, McCavigan AM, Logan GE, Walker SM, Steele CJ, Perner J, Bornschein J, MacRae S, Miremadi A, McCarron E, McQuaid S, Arthur K, James JA, Eatock MM, O'Neill R, Noble F, Underwood TJ, Harkin DP, Salto-Tellez M, Fitzgerald RC, Kennedy RD, Noorani A, Edwards PAW, Grehan N, Nutzinger B, Hughes C, Fidziukiewicz E, Crawte J, Northrop A, Contino G, Li X, de la Rue R, O'Donovan M, Malhotra S, Tripathi M, Tavare S, Lynch AG, Eldridge M, Bower L, Devonshire G, Jammula S, Davies J, Crichton C, Carroll N, Safranek P, Hindmarsh A, Sujendran V, Hayes SJ, Ang Y, Preston SR, Oakes S, Bagwan I, Save V, Skipworth RJE, Hupp TR, Tucker O, Beggs A, Taniere P, Puig S, Owsley J, Barr H, Shepherd N, Old O, Lagergren J, Gossage J, Davies A, Chang F, Zylstra J, Mahadeva U, Goh V, Ciccarelli FD, Sanders G, Berrisford R, Harden C, Lewis M, Cheong E, Kumar B, Parsons SL, Soomro I, Kaye P, Saunders J, Lovat L, Haidry R, Igali L, Scott M, Sothi S, Suortamo S, Lishman S, Hanna GB, Moorthy K, Peters CJ, Grabowska A, Coleman Het al., 2019, Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma, GUT, Vol: 68, Pages: 1918-1927, ISSN: 0017-5749

Journal article

Boshier PR, Swaray A, O'Sullivan A, Low DE, Hanna GB, Peters CJet al., 2019, Predictive models of survival after resection of oesophageal adenocarcinoma: a systematic review and multicentre validation of models, 22nd Annual Meeting of the Association-of-Upper-Gastrointestinal-Surgeons-of-Great-Britain-and-Ireland (AUGIS), Publisher: WILEY, Pages: 66-66, ISSN: 0007-1323

Conference paper

Mourikis TP, Benedetti L, Foxall E, Temelkovski D, Nulsen J, Perner J, Cereda M, Lagergren J, Howell M, Yau C, Fitzgerald RC, Scaffidi P, Noorani A, Edwards PAW, Elliott RF, Grehan N, Nutzinger B, Hughes C, Fidziukiewicz E, Bornschein J, MacRae S, Crawte J, Northrop A, Contino G, Li X, de la Rue R, Katz-Summercorn A, Abbas S, Loureda D, O'Donovan M, Miremadi A, Malhotra S, Tripathi M, Tavare S, Lynch AG, Eldridge M, Secrier M, Bower L, Devonshire G, Jammula S, Davies J, Crichton C, Carroll N, Safranek P, Hindmarsh A, Sujendran V, Hayes SJ, Ang Y, Sharrocks A, Preston SR, Oakes S, Bagwan I, Save V, Skipworth RJE, Hupp TR, O'Neill JR, Tucker O, Beggs A, Taniere P, Puig S, Underwood TJ, Walker RC, Grace BL, Barr H, Shepherd N, Old O, Gossage J, Davies A, Chang F, Zylstra J, Mahadeva U, Goh V, Sanders G, Berrisford R, Harden C, Lewis M, Cheong E, Kumar B, Parsons SL, Soomro I, Kaye P, Saunders J, Lovat L, Haidry R, Igali L, Scott M, Sothi S, Suortamo S, Lishman S, Hanna GB, Peters CJ, Moorthy K, Grabowska A, Turkington R, McManus D, Khoo D, Fickling W, Ciccarelli FDet al., 2019, Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma, Nature Communications, Vol: 10, Pages: 1-17, ISSN: 2041-1723

The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy.

Journal article

Frankell AM, Jammula S, Li X, Contino G, Killcoyne S, Abbas S, Perner J, Bower L, Devonshire G, Cocks E, Grehan N, Mok J, O'Donovan M, MacRae S, Eldridge MD, Tavare S, Fitzgerald RC, Noorani A, Edwards PAW, Grehanl N, Nutzinger B, Hughes CI, Fidziukiewicz E, Northrop A, de la Rue R, Katz-Summercorn A, Loureda D, Miremadi A, Malhotra S, Tripathi M, Lynch AG, Eldridge M, Secrier M, Davies J, Crichton C, Carro N, Safranek P, Hindmarsh A, Sujendran V, Hayes SJ, Ang Y, Sharrocks A, Preston SR, Oakes S, Bagwan I, Save V, Skipworth RJE, Hupp TR, ONeill JR, Tucker O, Beggs A, Taniere P, Puig S, Underwood T, Walker RC, Grace BL, Barr H, Shepherd N, Old O, Lagergren J, Gossage J, Davies A, Chang F, Zylstra J, Mahadeva U, Goh V, Ciccarelli FD, Sanders G, Berrisford R, Harden C, Lewis M, Cheong E, Kumar B, Parsons SL, Soomro I, Kaye P, Saunders J, Lovat L, Haidry R, Igali L, Scott M, Sothi S, Suortamo S, Lishman S, Hanna GB, Moorthy K, Peters CJ, Grabowska A, Turkington R, McManus D, Coleman H, Khoo D, Fickling Wet al., 2019, The landscape of selection in 551 esophageal adenocarcinomas defines genomic biomarkers for the clinic, Nature Genetics, Vol: 51, Pages: 506-516, ISSN: 1061-4036

Esophageal adenocarcinoma (EAC) is a poor-prognosis cancer type with rapidly rising incidence. Understanding of the genetic events driving EAC development is limited, and there are few molecular biomarkers for prognostication or therapeutics. Using a cohort of 551 genomically characterized EACs with matched RNA sequencing data, we discovered 77 EAC driver genes and 21 noncoding driver elements. We identified a mean of 4.4 driver events per tumor, which were derived more commonly from mutations than copy number alterations, and compared the prevelence of these mutations to the exome-wide mutational excess calculated using non-synonymous to synonymous mutation ratios (dN/dS). We observed mutual exclusivity or co-occurrence of events within and between several dysregulated EAC pathways, a result suggestive of strong functional relationships. Indicators of poor prognosis (SMAD4 and GATA4) were verified in independent cohorts with significant predictive value. Over 50% of EACs contained sensitizing events for CDK4 and CDK6 inhibitors, which were highly correlated with clinically relevant sensitivity in a panel of EAC cell lines and organoids.

Journal article

Sawas T, Killcoyne S, Iyer PG, Wang KK, Smyrk TC, Kisiel JB, Qin Y, Ahlquist DA, Rustgi AK, Costa RJ, Gerstung M, Fitzgerald RC, Katzka DA, OCCAMS Consortiumet al., 2018, Identification of Prognostic Phenotypes of Esophageal Adenocarcinoma in 2 Independent Cohorts., Gastroenterology, Vol: 155, Pages: 1720-1728.e4

BACKGROUND & AIMS: Most patients with esophageal adenocarcinoma (EAC) present with de novo tumors. Although this could be due to inadequate screening strategies, the precise reason for this observation is not clear. We compared survival of patients with prevalent EAC with and without synchronous Barrett esophagus (BE) with intestinal metaplasia (IM) at the time of EAC diagnosis. METHODS: Clinical data were studied using Cox proportional hazards regression to evaluate the effect of synchronous BE-IM on EAC survival independent of age, sex, TNM stage, and tumor location. We analyzed data from a cohort of patients with EAC from the Mayo Clinic (n=411; 203 with BE and IM) and a multicenter cohort from the United Kingdom (n=1417; 638 with BE and IM). RESULTS: In the Mayo cohort, BE with IM had a reduced risk of death compared to patients without BE and IM (hazard ratio [HR] 0.44; 95% CI, 0.34-0.57; P<.001). In a multivariable analysis, BE with IM was associated with longer survival independent of patient age or sex, tumor stage or location, and BE length (adjusted HR, 0.66; 95% CI, 0.5-0.88; P=.005). In the United Kingdom cohort, patients BE and IM had a reduced risk of death compared with those without (HR, 0.59; 95% CI, 0.5-0.69; P<.001), with continued significance in multivariable analysis that included patient age and sex and tumor stage and tumor location (adjusted HR, 0.77; 95% CI, 0.64-0.93; P=.006). CONCLUSION: Two types of EAC can be characterized based on the presence or absence of BE. These findings could increase our understanding the etiology of EAC, and be used in management and prognosis of patients.

Journal article

Waldock WJ, Avila-Rencoret FB, Tincknell LG, Murphy J, Elson DS, Peters CJet al., 2018, Augmented intraoperative surgical vision for the assessment of gastrointestinal cancer resection margins, 21st Annual Meeting of the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS), Publisher: Wiley, Pages: 15-16, ISSN: 1365-2168

Conference paper

Savva K-V, Doran SLF, Boshier PR, Gummet P, Hanna GB, Peters CJet al., 2018, Small bowel bacterial overgrowth is common in asymptomatic patients following Gastrointestinal surgery, 21st Annual Meeting of the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS), Publisher: Wiley, Pages: 31-31, ISSN: 1365-2168

Conference paper

Brunckhorst O, Guidozzi NM, Warren LR, Peters CJet al., 2018, Tension haemothorax from a bleeding branch of the renal artery following isolated penetrating thoracic trauma: a rare presentation., BMJ Case Rep, Vol: 2018

A 27-year-old man presented to a major trauma centre with two posterolateral thoracic stab injuries over the right scapula and thoracoabdominal junction. He was tachycardic and hypotensive with a chest X-ray revealing a large right-sided tension haemothorax, requiring insertion of two intercostal chest drains. A subsequent CT scan demonstrated a grade 4 right kidney laceration with active back bleeding from a renal artery branch, through a right diaphragmatic defect, into the pleural cavity. Embolisation of the feeding renal vessel controlled the bleeding and avoided the need for a nephrectomy. The patient required subsequent video-assisted thoracoscopic evacuation of the haemothorax and diaphragmatic repair, confirming that there was no associated lung or major vessel injury. A ureteric stent was ultimately inserted to manage a persistent urinary leak. This case highlights a rare cause for a common traumatic presentation and the need for a multidisciplinary approach in effective management of complex, multiorgan trauma.

Journal article

Whibley J, Peters CJ, Halliday LJ, Chaudry AM, Allum WHet al., 2018, Poor performance in incremental shuttle walk and cardiopulmonary exercise testing predicts poor overall survival for patients undergoing esophago-gastric resection, EJSO - European Journal of Surgical Oncology, Vol: 44, Pages: 594-599, ISSN: 0748-7983

Introduction: Esophageal and gastric cancer have a poor prognosis and surgical intervention is associated with considerable morbidity, highlighting the need for careful preoperative assessment. The Incremental Shuttle Walk Test (ISWT) and Cardiopulmonary exercise testing (CPET) can assess preoperative fitness. This study aims to investigate their correlation with both postoperative respiratory complications and overall survival. Patients and methods: Patients were identified who underwent esophageal or gastric resections for cancer between 2010 and 2014 and had ISWT and/or CPET assessments. Tumor differentiation, stage, postoperative respiratory complications, and outcome were documented and then correlated with the results of the preoperative fitness assessments. Results: Neither the ISWT result, anaerobic threshold (AT) nor VO2 Max correlated well with perioperative complications. However, ISWT (p < 0.001), AT (p < 0.001) and VO2 Max (p < 0.001) all correlated strongly with overall survival. No patient with a score of less than 350 m on ISWT survived beyond 3 years. In a subset of patients with ISWT results both pre and post chemotherapy (n = 49), those that had an improvement in result had a 19% incidence of post-operative respiratory complications compared to 45% where the result did not change or declined, though due to small numbers this only approached significance (p = 0.08). Conclusion: ISWT and CPET can be useful preoperative tools to predict overall survival for patients undergoing esophago-gastric resection. Furthermore, patients that improve their functional status during chemotherapy seem to do better than those where it remains static or declines.

Journal article

Blayney JK, Cairns L, Li G, McCabe N, Stevenson L, Peters CJ, Reid NB, Spence VJ, Chisambo C, McManus D, James J, McQuaid S, Craig S, Arthur K, McArt D, Ong CJ, Lao-Sirieix P, Hamilton P, Salto-Tellez M, Eatock M, Coleman HG, Fitzgerald RC, Kennedy RD, Turkington RC, On behalf of the Oesophageal Cancer Clinical and Molecular Stratification OCCAMS Study Groupet al., 2018, Glucose transporter 1 expression as a marker of prognosis in oesophageal adenocarcinoma, Oncotarget, Vol: 9, Pages: 18518-18528, ISSN: 1949-2553

Background: The current TNM staging system for oesophageal adenocarcinoma (OAC) has limited ability to stratify patients and inform clinical management following neo-adjuvant chemotherapy and surgery.Results: Functional genomic analysis of the gene expression data using Gene Set Enrichment Analysis (GSEA) identified GLUT1 as putative prognostic marker in OAC.In the discovery cohort GLUT1 positivity was observed in 114 patients (80.9%) and was associated with poor overall survival (HR 2.08, 95% CI 1.1-3.94; p=0.024) following multivariate analysis. A prognostic model incorporating GLUT1, CRM and nodal status stratified patients into good, intermediate and poor prognosis groups (p< 0.001) with a median overall survival of 16.6 months in the poorest group.In the validation set 182 patients (69.5%) were GLUT1 positive and the prognostic model separated patients treated with neo-adjuvant chemotherapy and surgery (p<0.001) and surgery alone (p<0.001) into three prognostic groups.Patients and Methods: Transcriptional profiling of 60 formalin fixed paraffin-embedded (FFPE) biopsies was performed. GLUT1 immunohistochemical staining was assessed in a discovery cohort of 141 FFPE OAC samples treated with neo-adjuvant chemotherapy and surgery at the Northern Ireland Cancer Centre from 2004-2012. Validation was performed in 262 oesophageal adenocarcinomas collected at four OCCAMS consortium centres. The relationship between GLUT1 staining, T stage, N stage, lymphovascular invasion and circumferential resection margin (CRM) status was assessed and a prognostic model developed using Cox Proportional Hazards.Conclusions: GLUT1 staining combined with CRM and nodal status identifies a poor prognosis sub-group of OAC patients and is a novel prognostic marker following potentially curative surgical resection.

Journal article

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