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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Publications

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35 results found

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

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

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

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

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

Elson D, Tincknell L, Avila Rencoret F, Murphy J, Peters Cet al., 2018, Intraoperative hyperspectral circumferential resection margin assessment for gastrointestinal cancer surgery (second prize), Career in Surgery

Conference paper

Waldock W, Avila Rencoret F, Tincknell L, Murphy J, Elson D, Peters Cet al., 2018, Augmented intraoperative surgical vision for the assessment of gastrointestinal cancer resection margins, London Surgery Symposium

Conference paper

Wormald JC, Dindyal S, Thomas R, Peters CJ, Sritharan Ket al., 2017, Aorto-esophageal fistula: the multi-disciplinary team approach to management, Clinical Case Reports, Vol: 4, Pages: 800-802, ISSN: 2050-0904

Aorto-esophageal fistula is often a terminal event in many patients. The commonest causes are thoracic aortic aneurysm and esophageal malignancy. To achieve a good outcome in this condition, a MDT approach is required that combines the expertize of vascular surgeons, radiologists, and emergency physicians.

Journal article

Tincknell L, Avila Rencoret F, Murphy J, Peters C, Elson Det al., 2017, Intraoperative hyperspectral circumferential resection margin assessment for gastrointestinal cancer surgery, London Surgery Symposium

Conference paper

Tucker O, Peters CJ, Zohra R, Nepogodiev D, Moorthy Ket al., 2016, A multicentre prospective observational cohort study to determine factors associated with postoperative pneumonia in patients undergoing oesophago-gastric resections, 19th Annual Scientific Meeting of the Association-of-Upper-Gastrointestinal-Surgeons-of-Great-Britain-and-Ireland, Publisher: Wiley, Pages: 39-39, ISSN: 1365-2168

Conference paper

Peters CJ, Drake T, Kong C, Moorthy K, Tucker Oet al., 2016, Multicentre national observational cohort study on variation in peri-operative care pathways following major oesophago-gastric resection, 19th Annual Scientific Meeting of the Association-of-Upper-Gastrointestinal-Surgeons-of-Great-Britain-and-Ireland, Publisher: WILEY-BLACKWELL, Pages: 47-47, ISSN: 0007-1323

Conference paper

Paterson AL, Shannon NB, Lao-Sirieix P, Ong C-AJ, Peters CJ, O'Donovan M, Fitzgerald RCet al., 2013, A systematic approach to therapeutic target selection in oesophago-gastric cancer, Gut, Vol: 62, Pages: 1415-1424, ISSN: 0017-5749

PDFUpper GI cancerOriginal articleA systematic approach to therapeutic target selection in oesophago-gastric cancerFree Anna L Paterson1, Nicholas B Shannon1, Pierre Lao-Sirieix1, Chin-Ann J Ong1, Christopher J Peters1, Maria O'Donovan1,2, Rebecca C Fitzgerald1Author affiliationsAbstractObjective The success of personalised therapy depends on identification and inhibition of the oncogene(s) on which that tumour is dependent. We aimed to determine whether a receptor tyrosine kinase (RTK) array could be used to select the most effective therapeutic strategies in molecularly heterogeneous oesophago-gastric adenocarcinomas.Design Gene expression profiling from oesophago-gastric tumours (n=75) and preinvasive stages (n=57) identified the active signalling pathways, which was confirmed using immunohistochemistry (n=434). RTK arrays on a cell line panel (n=14) determined therapeutic targets for in vitro cytotoxic testing. Feasibility of this personalised approach was tested in tumour samples (n=46).Results MAPK was the most frequently activated pathway (32/75 samples (42.7%)) with progressive enrichment in preinvasive disease stages (p<0.05) and ERK phosphorylation in 148/434 (34.3%) independent samples. Cell lines displayed a range of RTK activation profiles. When no RTKs were activated, tyrosine kinase inhibitors (TKIs) and a Mek inhibitor were not useful (MKN1). In lines with a dominant phosphorylated RTK (OE19, MKN45 and KATOIII), selection of this TKI or Mek in nM concentrations induced cytotoxicity and inhibited Erk and Akt phosphorylation. In cells lines with complex activation profiles (HSC39 and OE33), a combination of TKIs or Mek inhibition (in nM concentrations) was necessary for cytotoxicity and inhibition of Erk and Akt phosphorylation. Human tumours demonstrated diverse activation profiles and 65% of cases had two or more active RTKs.Conclusions The MAPK pathway is commonly activated in oesophago-gastric cancer following activation of a variety of RTKs.

Journal article

Zamani A, Peters CJ, Chadwick SJ, 2013, The use of an ex vivo contrast study at the time of surgery to confirm the site of a perforated jejunal diverticulum., BMJ Case Rep, Vol: 2013

A 63-year-old patient was diagnosed with acute jejunal diverticulitis and possible perforation. The patient was taken to the operating room for an exploratory laparotomy where a suspected segment of small bowel was resected. However, the surgical team was unsure whether the resected segment was the definite location of the perforation. A novel technique; using intraoperative contrast enhanced ex vivo x-ray photographs aided the surgical team in finding the exact location of the perforation and thus allowing the operating team to confidently and safely proceed with closure of the abdomen.

Journal article

King A, Peters CJ, Shorvon P, 2012, Acute pancreatitis with pancreatic abscess secondary to sealed jejunal diverticular perforation., BMJ Case Rep, Vol: 2012

Although most cases of acute pancreatitis are attributed to gallstones or alcohol, many remain idiopathic. The authors describe a case of acute pancreatitis in a 75-year-old gentleman who presented with acute epigastric pain, fevers and shortness of breath. Serum amylase was 2164. CT showed free mesenteric air, and a partly cystic/partly gas-containing mass in the uncinate lobe of the pancreas. Gastrograffin meal revealed duodenal and jejunal diverticular disease, but no contrast leak. Further CT analysis pinpointed fine tracts of air leading from a jejunal diverticulum up toward the pancreas, suggesting causation by a sealed jejunal diverticular perforation. He responded well to intravenous antibiotics and conservative management. Although small bowel diverticular disease is linked to chronic pancreatitis, evidence for association with acute pancreatitis is scarce. The authors believe this is the first reported case of jejunal diverticular disease causing acute pancreatitis, and it highlights micro-perforation as a potential disease mechanism.

Journal article

Rollins KE, Peters CJ, Safranek PM, Ford H, Baglin TP, Hardwick RHet al., 2011, Venous thromboembolism in oesophago-gastric carcinoma: Incidence of symptomatic and asymptomatic events following chemotherapy and surgery, EJSO, Vol: 37, Pages: 1072-1077, ISSN: 0748-7983

Journal article

Paterson AL, Shannon NB, Lao-Sirieix P, Peters CJ, O'Donovan M, Fitzgerald RCet al., 2011, A SYSTEMATIC APPROACH TO THERAPEUTIC TARGET SELECTION IN GASTRO-ESOPHAGEAL ADENOCARCINOMA, Annual Meeting on British-Society-of-Gasenterology, Publisher: B M J PUBLISHING GROUP, Pages: A20-A20, ISSN: 0017-5749

Conference paper

Ujam AB, Peters CJ, Tadrous PJ, Webster JJ, Steer K, Martinez-Isla Aet al., 2011, Adrenal pseudocyst: Diagnosis and laparoscopic management - A case report., Int J Surg Case Rep, Vol: 2, Pages: 306-308

Cysts of the adrenal gland are rare and are usually discovered incidentally. Large adrenal cysts can however present with severe abdominal pain and can be complicated by haemorrhage, rupture or infection. Adrenal pseudocysts appear to result from haemorrhage within a normal adrenal gland and can expand to accommodate massive amounts of fluid.We report the case of a 39-year-old woman who presented with worsening right upper quadrant pain. An ultrasound scan of the abdomen confirmed a large 29 cm × 20 cm × 17 cm cyst that appeared to originate in the upper pole of the right kidney causing displacement of the liver and right kidney.Following complete aspiration the cyst re-accumulated and an MRI scan demonstrated a thickened and irregular cyst wall with haemorrhagic fluid. Laparoscopic right adrenalectomy was performed and the histopathological diagnosis was confirmed as an adrenal pseudocyst.

Journal article

Peters CJ, Rees JRE, Hardwick RH, Hardwick JS, Vowler SL, Ong C-AJ, Zhang C, Save V, O'Donovan M, Rassl D, Alderson D, Caldas C, Fitzgerald RCet al., 2010, A 4-Gene Signature Predicts Survival of Patients With Resected Adenocarcinoma of the Esophagus, Junction, and Gastric Cardia, GASTROENTEROLOGY, Vol: 139, Pages: 1995-U280, ISSN: 0016-5085

Journal article

Peters CJ, Rees JRE, Hardwick JS, Vowler SL, Ong CJ, Zhang C, Save V, O'Donovan M, Rassl D, Caldas C, Alderson D, Hardwick RH, Fitzgerald RCet al., 2010, A CLINICALLY APPLICABLE THREE GENE SIGNATURE IS INDEPENDENTLY HIGHLY PROGNOSTIC IN OESOPHAGEAL AND JUNCTIONAL ADENOCARCINOMA, Annual General Meeting of the British-Society-of-Gastroenterology, Publisher: B M J PUBLISHING GROUP, Pages: A24-A25, ISSN: 0017-5749

Conference paper

Peters CJ, Hardwick RH, Vowler SL, Fitzgerald RCet al., 2009, Generation and validation of a revised classification for oesophageal and junctional adenocarcinoma, BRITISH JOURNAL OF SURGERY, Vol: 96, Pages: 724-733, ISSN: 0007-1323

Journal article

Peters CJ, Hardwick RH, Vowler SL, Fitzgerald RCet al., 2009, LYMPH NODE LOCATION IMPROVES THE PROGNOSTIC POWER OF OESOPHAGEAL ADENOCARCINOMA STAGING, Annual Meeting of the British-Society-of-Gastroenterology, Publisher: B M J PUBLISHING GROUP, Pages: A45-A45, ISSN: 0017-5749

Conference paper

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