Publications
81 results found
Kazachenka A, Loong JH, Attig J, et 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.
Abbas S, Pich O, Devonshire G, et al., 2023, Mutational signature dynamics shaping the evolution of oesophageal adenocarcinoma., Nat Commun, Vol: 14
A variety of mutational processes drive cancer development, but their dynamics across the entire disease spectrum from pre-cancerous to advanced neoplasia are poorly understood. We explore the mutagenic processes shaping oesophageal adenocarcinoma tumorigenesis in 997 instances comprising distinct stages of this malignancy, from Barrett Oesophagus to primary tumours and advanced metastatic disease. The mutational landscape is dominated by the C[T > C/G]T substitution enriched signatures SBS17a/b, which are linked with TP53 mutations, increased proliferation, genomic instability and disease progression. The APOBEC mutagenesis signature is a weak but persistent signal amplified in primary tumours. We also identify prevalent alterations in DNA damage repair pathways, with homologous recombination, base and nucleotide excision repair and translesion synthesis mutated in up to 50% of the cohort, and surprisingly uncoupled from transcriptional activity. Among these, the presence of base excision repair deficiencies show remarkably poor prognosis in the cohort. In this work, we provide insights on the mutational aetiology and changes enabling the transition from pre-neoplastic to advanced oesophageal adenocarcinoma.
Gkouzionis I, Zhong Y, Nazarian S, et al., 2023, A YOLOv5-based network for the detection of a diffuse reflectance spectroscopy probe to aid surgical guidance in gastrointestinal cancer surgery, Int J Comput Assist Radiol Surg
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.
Booth ME, Jones CM, Helbrow J, et al., 2023, The UK National Oesophagogastric Multidisciplinary Team Meeting: an initiative from the UK & Ireland Oesophagogastric Group, Clinical Oncology, ISSN: 0936-6555
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
Moorthy K, Halliday LJ, Noor N, et 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.
Peters CJ, Bonanomi G, Fehervari M, et 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.
Baggaley AE, Lafaurie GBRC, Tate SJ, et 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
Savva K-V, Das B, Antonowicz S, et 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.
Case A, Prosser S, Peters CJ, et 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.
Nazarian S, Gkouzionis I, Kawka M, et 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
Elson D, Nazarian S, Gkouzionis I, et al., 2022, Real-time Classification of Colorectal Tissue Using Diffuse Reflectance Spectroscopy to Aid Margin Assessment, European Society of Coloproctology Scientific Conference
Salem V, Hirani D, Lloyd C, et 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.
Boshier PR, Swaray A, Vadhwana B, et 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.
Ng AWT, Contino G, Killcoyne S, et 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.
Sivakumar J, Forshaw MJ, Lam S, et 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.
Gkouzionis I, Nazarian S, Kawka M, et 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.
Elson D, Gkouzionis I, Nazarian S, et al., 2022, Using diffuse reflectance spectroscopy for real-time tissue assessment during upper gastrointestinal cancer surgery, IEEE International Conference on Biomedical and Health Informatics
Gkouzionis I, Nazarian S, Darzi A, et al., 2022, Discriminating between cancer and healthy tissue in upper gastrointestinal cancer surgery using deep learning and diffuse reflectance spectroscopy, London Surgery Symposium
Gkouzionis I, Nazarian S, Kawka M, et 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
Gkouzionis I, Nazarian S, Darzi A, et 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
Gkouzionis I, Nazarian S, Patel N, et 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.
Elson D, Gkouzionis I, Nazarian S, et 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
Nazarian S, Gkouzionis I, Kawka M, et 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
Gkouzionis I, Nazarian S, Anandakumar A, et 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.
Ococks E, Sharma S, Ng AWT, et 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, ISSN: 0016-5085
Savva K-V, Hage L, Belluomo I, et 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
Nazarian S, Gkouzionis I, Anandakumar A, et 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.
Antonowicz S, Bodai Z, Wiggins T, et 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.
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