Publications by authors named "S Antonowicz"

24 Publications

Patient-reported outcomes after oesophagectomy in the multicentre LASER study.

Br J Surg 2021 May 11. Epub 2021 May 11.

Oesophago-gastric Centre, Churchill Hospital, University of Oxford, Oxford, UK.

Background: Data on the long-term symptom burden in patients surviving oesophageal cancer surgery are scarce. The aim of this study was to identify the most prevalent symptoms and their interactions with health-related quality of life.

Methods: This was a cross-sectional cohort study of patients who underwent oesophageal cancer surgery in 20 European centres between 2010 and 2016. Patients had to be disease-free for at least 1 year. They were asked to complete a 28-symptom questionnaire at a single time point, at least 1 year after surgery. Principal component analysis was used to assess for clustering and association of symptoms. Risk factors associated with the development of severe symptoms were identified by multivariable logistic regression models.

Results: Of 1081 invited patients, 876 (81.0 per cent) responded. Symptoms in the preceding 6 months associated with previous surgery were experienced by 586 patients (66.9 per cent). The most common severe symptoms included reduced energy or activity tolerance (30.7 per cent), feeling of early fullness after eating (30.0 per cent), tiredness (28.7 per cent), and heartburn/acid or bile regurgitation (19.6 per cent). Clustering analysis showed that symptoms clustered into six domains: lethargy, musculoskeletal pain, dumping, lower gastrointestinal symptoms, regurgitation/reflux, and swallowing/conduit problems; the latter two were the most closely associated. Surgical approach, neoadjuvant therapy, patient age, and sex were factors associated with severe symptoms.

Conclusion: A long-term symptom burden is common after oesophageal cancer surgery.
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http://dx.doi.org/10.1093/bjs/znab124DOI Listing
May 2021

Endogenous aldehyde accumulation generates genotoxicity and exhaled biomarkers in esophageal adenocarcinoma.

Nat Commun 2021 03 5;12(1):1454. Epub 2021 Mar 5.

Department of Surgery and Cancer, Imperial College London, London, UK.

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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http://dx.doi.org/10.1038/s41467-021-21800-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935981PMC
March 2021

Gastrointestinal side effects of upper gastrointestinal cancer surgery.

Best Pract Res Clin Gastroenterol 2020 Oct - Dec;48-49:101706. Epub 2020 Nov 10.

Oxford Oesophago Gastric Centre, Oxford University Hospitals NHS Trust, UK. Electronic address:

In this chapter, we describe the gastrointestinal side effects of oesophagectomy, gastrectomy and pancreaticoduodenectomy for cancer, with a focus on long-term functional impairments and their management. Improvements in upper gastrointestinal cancer surgery have led to a growing group of long-term survivors. The invasive nature of these surgeries profoundly alters the upper gastrointestinal anatomy, with lasting implications for long-term function, and how these impairments may be treated. Successfully maintaining a high quality of survivorship requires multidisciplinary approach, with survivorship care plans focused on function as much as the detection of recurrence.
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http://dx.doi.org/10.1016/j.bpg.2020.101706DOI Listing
January 2021

Metabolic Biomarkers of Squamous Cell Carcinoma of the Aerodigestive Tract: A Systematic Review and Quality Assessment.

Oxid Med Cell Longev 2020 21;2020:2930347. Epub 2020 Feb 21.

Department of Surgery & Cancer, Imperial College London, London W2 1NY, UK.

Aerodigestive squamous cell carcinomas (ASCC) constitute a major source of global cancer deaths. Patients typically present with advanced, incurable disease, so new means of detecting early disease are a research priority. Metabolite quantitation is amenable to point-of-care analysis and can be performed in ASCC surrogates such as breath and saliva. The purpose of this systematic review is to summarise progress of ASCC metabolomic studies, with an emphasis on the critical appraisal of methodological quality and reporting.

Method: A systematic online literature search was performed to identify studies reporting metabolic biomarkers of ASCC. This review was conducted in accordance with the recommendations of the Cochrane Library and MOOSE guidelines.

Results: Thirty studies comprising 2117 patients were included in the review. All publications represented phase-I biomarker discovery studies, and none validated their findings in an independent cohort. There was heterogeneity in study design and methodological and reporting quality. Sensitivities and specificities were higher in oesophageal and head and neck squamous cell carcinomas compared to those in lung squamous cell carcinoma. The metabolic phenotypes of these cancers were similar, as was the kinetics of metabolite groups when comparing blood, tissue, and breath/saliva concentrations. Deregulation of amino acid metabolism was the most frequently reported theme.

Conclusion: Metabolite analysis has shown promising diagnostic performance, especially for oesophageal and head and neck ASCC subtypes, which are phenotypically similar. However, shortcomings in study design have led to inconsistencies between studies. To support future studies and ultimately clinical adoption, these limitations are discussed.
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http://dx.doi.org/10.1155/2020/2930347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330643PMC
May 2021

Lasting Symptoms After Esophageal Resection (LASER): European Multicenter Cross-sectional Study.

Ann Surg 2020 Nov 17. Epub 2020 Nov 17.

Department of Upper GI Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Objective: To identify the most prevalent symptoms and those with greatest impact upon health-related quality of life (HRQOL) among esophageal cancer survivors.

Background: Long-term symptom burden after esophagectomy, and associations with HRQOL, are poorly understood.

Patients And Methods: Between 2010 and 2016, patients from 20 European Centers who underwent esophageal cancer surgery, and were disease-free at least 1 year postoperatively were asked to complete LASER, EORTC-QLQ-C30, and QLQ-OG25 questionnaires. Specific symptom questionnaire items that were associated with poor HRQOL as identified by EORTC QLQ-C30 and QLQ-OG25 were identified by multivariable regression analysis and combined to form a tool.

Results: A total of 876 of 1081 invited patients responded to the questionnaire, giving a response rate of 81%. Of these, 66.9% stated in the last 6 months they had symptoms associated with their esophagectomy. Ongoing weight loss was reported by 10.4% of patients, and only 13.8% returned to work with the same activities.Three LASER symptoms were correlated with poor HRQOL on multivariable analysis; pain on scars on chest (odds ratio (OR) 1.27; 95% CI 0.97-1.65), low mood (OR 1.42; 95% CI 1.15-1.77) and reduced energy or activity tolerance (OR 1.37; 95% CI 1.18-1.59). The areas under the curves for the development and validation datasets were 0.81 ± 0.02 and 0.82 ± 0.09 respectively.

Conclusion: Two-thirds of patients experience significant symptoms more than 1 year after surgery. The 3 key symptoms associated with poor HRQOL identified in this study should be further validated, and could be used in clinical practice to identify patients who require increased support.
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http://dx.doi.org/10.1097/SLA.0000000000003917DOI Listing
November 2020