bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-OGC29 Pathological response profiles of FLOT and ECX neoadjuvant chemotherapy in oesophageal adenocarcinoma
Authors: Knight William , Pepas Arion , Lee Melody , Hlukha Larysa , Jackson Andrew , Hossain Tanvir , Theophilidou Elena , Yanni Fady , Vohra Ravi , Parsons Simon 
Published: December 2021

Abstract

Background
70% of patients undergoing neo-adjuvant ECX chemotherapy for adenocarcinoma of the oesophagus, show little to know response in their primary tumour (Mandard 4,5). However, among these patients, those who have a complete nodal response (cN+ to ypN0) have equivalent survival to those with Mandard 1,2,3 tumours. FLOT chemotherapy has shown a survival advantage to ECX, however, rates of primary tumour response and nodal response are yet to be the focus of published study.

Methods
Retrospective cohort study comparing patients undergoing ECX and FLOT neoadjuvant chemotherapy between 2014 and 2021. Pathological outcomes were examined including, Mandard tumour regression grade (1-5), complete nodal response (cN+ to ypN0), clinically node negative nodal progression (cN0 to ypN+).

Results
226 patients had data available for analysis (193 ECX and 33 FLOT). 27% (52/193) of patients receiving ECX showed a response in the primary tumour (Mandard 1,2,3) compared to 63% (21/33) with patients undergoing FLOT (p &lt; 0.001). Complete nodal response rates were 25% in ECX patients and 21% FLOT patients (p = 0.556). Clinically node negative nodal upstaging (cN0 to pN+) was higher among FLOT patients 30% (13/33) than ECX patients 12% (24/193) (p &lt; 0.001).

Conclusions
FLOT chemotherapy confers improved primary tumour response. However, these findings were not echoed in locoregional nodal responses. Survival advantages with FLOT may result from improved responses in primary tumour and not improved systemic coverage. More data will be needed to explore this and over-come the confounding effect of staging inaccuracies. However, understanding systemic and loco-regional responses of different chemotherapy regimens will be needed to tailor future neoadjuvant treatment regimens.
P-OGC32 Copper-dependent cell death is a cancer specific vulnerability in oesophageal adenocarcinoma and provides the opportunity for future biomarker-stratified clinical trials
Authors: Hughes Rebecca E , Elliott Richard JR , Munro Alison , Hupp Ted , Carragher Neil O , O'Neill J Robert 
Published: December 2021

Abstract

Background
Oesophageal adenocarcinoma (OAC) is of increasing global concern due to increasing incidence, lack of effective treatments, and poor prognosis. Therapeutic target discovery and clinical trials have been hindered by the heterogeneity of the disease, dominance of large-scale genomic rearrangements, and lack of driver mutations. We have profiled small-molecule compounds using an innovative high content imaging assay in a panel of transformed and non-transformed oesophageal cell lines to identify OAC-specific cytotoxic compounds, new therapeutic targets, potential drug repurposing opportunities, and chemical starting points for the treatment of OAC.

Methods
We have comprehensively profiled 19,555 small-molecule compounds using an innovative high content assay to quantify 1000’s of subcellular imaging features to capture important phenotypes missed by standard approaches. Prioritised molecules then underwent functional, transcriptomic, and metabolomic characterisation across panels of oesophageal cell lines and patient-derived organoids for the identification of OAC-specific drug mechanisms.

Results
We identified 72 lead compounds as exhibiting OAC-specific cytotoxicity and characterised three of the most potent and selective compounds in depth, each of different proposed classes and chemical structures. Using several orthogonal methods we uncovered a unified mechanism of action and a targetable vulnerability in OAC involving copper-dependent cell death. Strikingly no phenotypic effects or changes in gene-expression were observed following treatment with these compounds in non-transformed oesophageal cell lines or normal gastric organoids providing support for this mechanism as a cancer-specific phenomenon.

Conclusions
We have applied high content imaging, transcriptomic and metabolomic analyses to reveal a unique vulnerability in OAC. We have defined a unified mechanism of OAC-specific copper-dependent cell death for the three highly potent compounds. Finally, through the integration of transcriptomic and metabolomics analyses we gained insight into drug sensitivity and provide the basis for a future biomarker-stratified clinical trial of these drugs in OAC.
P-OGC39 The smell of oesophageal adenocarcinoma: opportunities for tests and treatments
Authors: Antonowicz Stefan , Abbassi-Ghadi Nima , Bodai Zsolt , Wiggins Tom , Markar Sheraz , Boshier Piers , Goh Yan Mei , Adam Mina , Lu Haonan , Kudo Hiromi , Rosini Francesca , Goldin Robert , Moralli Daniella , Green Catherine , Peters Chris , Habib Nagy , Gabra Hani , Fitzgerald Rebecca , Takats Zoltan , Hanna George 
Published: December 2021

Abstract

Background
Exhaled breath analysis is a promising approach for oesophageal adenocarcinoma (OAC) early detection. The biomarkers of interest are low molecular weight metabolites including volatile aldehydes. In this translational study we investigated whether these metabolites originated from a tumoral source, and how this might impact the diagnosis and treatment of OAC patients.

Methods
The investigative strategy was directed by an unbiased informatics screen of metabolic reprogramming in OAC, and validated using complimentary gene expression assays (n = 638, including controls). Mass spectrometric methods were used to quantify corresponding metabolites and putative source compounds at a tissue level (n = 158), and also in exhaled breath for correlative purposes. Targeted in vitro experiments were performed to demonstrate the cause and effect of the proposed model of metabolic reprogramming in OAC.

Results
The unbiased screen and subsequent validation found that reduced aldehyde detoxification is an OAC hallmark. In vitro and in vivo this was associated with endogenous aldehyde accumulation. OAC tissue was generally enriched for volatile aldehydes, including the genotoxins formaldehyde, acetaldehyde, 4-hydroxy-2-nonenal and 2-butenal, and the exhaled biomarker decanal (all P &lt; 0.0001). Decanal concentrations correlated with exhaled concentrations. Considering potential aldehyde sources, the OAC phospholipidome was characterised by desaturated and longer lipid acyls, and these spontaneously generated biomarker aldehyde species at ambient conditions. Enriched genotoxic aldehydes were detectable in base-pairing positions in DNA; this genotoxicity was therapeutically targetable with aldehyde scavengers in vitro.

Conclusions
These data support a model for enriched exhaled aldehydes based on increased production from an altered lipid phenotype, and reduced detoxification. Some aldehydes are non-reactive and thus support non-invasive detection. Others react with DNA and increase local genotoxicity; this process is druggable. These findings have implications for OAC early diagnosis and chemoprevention.
P-OGC41 Survival after curative chemoradiotherapy or neoadjuvant therapy and surgery converges in higher-risk patients with oesophageal cancer
Authors: Rana Mridul , Sanga Akshata , Sgromo Bruno , Gillies Richard , Marshall Robert , Maynard Nick , Ash Stephen , Antonowicz Stefan , Owen Richard 
Published: December 2021

Abstract

Background
Both curative chemoradiotherapy (cCRT) and neoadjuvant chemoradiotherapy and surgery (nCRTS) can be considered as treatments for potentially curable oesophageal squamous cell carcinoma (OSCC). Whilst this equipoise does not exist in oesophageal adenocarcinoma (OAC), there are patients in whom treatment decisions are not straightforward, creating an overlapping group in which cCRT might be considered in preference to neoadjuvant chemotherapy or chemoradiotherapy and surgery (nC(R)TS). We aim to see how survival changes between unmatched and matched cohorts of patients with OAC and OSCC treated with cCRT or nC(R)TS, to reflect difficult multidisciplinary team treatment decisions.

Methods
Patients treated with nC(R)TS or cCRT for OSCC and OAC were identified on an intention-to-treat basis from April 2016 to April 2019, allowing a minimum 2-year follow up from diagnosis. Upper third tumours were excluded due to clear preference for cCRT. Preoperative variables were compared using descriptive statistics, with OSCC and OAC analysed separately. Significantly different variables were used to generate propensity scores. Cohorts were then matched and analysis repeated to assess cohort symmetry. Overall survival and 2-year survival were investigated using Kaplan-Meier survival curves and log-rank testing. Analysis was performed in R.

Results
60 and 231 patients with OSCC and OAC were treated with cCRT or nC(R)TS. In the unmatched analysis, nC(R)TS had superior overall and 2-year survival, however there were significant differences in age, Charlson comorbidity index and cancer stage in OSCC and OAC cohorts, and in tumour site for the OAC cohort. After propensity score matching, differences in overall and 2-year survival reduced, though no results reached significance (OSCC: nCRTS 2y survival 58% vs 51% and 54% in unmatched and matched cCRT cohorts, respectively; OAC: cCRT 2y survival 51% vs 60% and 56% in unmatched and matched nC(R)TS cohorts, respectively).

Conclusions
These data suggest that as patient and cancer related factors increase the difficulty of treatment decisions, the survival benefit of surgery reduces in both OSCC and OAC. These results underline the need for randomised controlled trials using current treatment and staging strategies, as there have been considerable advances since original comparisons of neoadjuvant and curative chemoradiotherapy. This study is limited by relatively short follow up and unpowered sample sizes, however the coded nature of the analysis provides a structure for regular review of outcomes in our unit using routinely collected data, and could be easily applied more widely.
P-OGC46 Physiotherapy Regimens in Esophagectomy and Gastrectomy: a Systematic Review and Meta-analysis
Authors: Tukanova Karina , Chidambaram Swathikan , Guidozzi Nadia , Hanna George , McGregor Alison , Markar Sheraz 
Published: December 2021

Abstract

Background
Esophageal and gastric cancer surgery are associated with considerable morbidity, specifically postoperative pulmonary complications (PPC), potentially accentuated by underlying challenges with malnutrition and cachexia affecting respiratory muscle mass. Physiotherapy regimens aim to increase the respiratory muscle strength and may prevent postoperative morbidity. This meta-analysis aims to assess the impact of physiotherapy regimens following esophagectomy or gastrectomy.

Methods
An electronic database search was performed in MEDLINE, EMBASE, CENTRAL, CINAHL and Pedro databases. A meta-analysis was performed to assess the impact of physiotherapy on the functional capacity, incidence of PPC and postoperative morbidity, in-hospital mortality rate, the Length of Hospital Stay (LOS) and the Health-Related Quality of Life (HRQoL).

Results
Seven RCTs and 7 cohort studies assessing prehabilitation totalling 960 patients, and 5 RCTs and 5 cohort studies assessing peri- or postoperative physiotherapy with 703 total patients, were included. Prehabilitation resulted in a lower incidence of postoperative pneumonia and morbidity (Clavien-Dindo score &gt;II). No difference was observed in functional exercise capacity, and in-hospital mortality following prehabilitation. Meanwhile, peri- or postoperative rehabilitation resulted in a lower incidence of pneumonia, a shorter LOS and better HRQoL scores for dyspnea and physical functioning, while no differences were found for the QoL summary score, global health status, fatigue and pain scores.

Conclusions
Our meta-analysis shows that implementing an exercise intervention may be beneficial in both the preoperative and peri- or postoperative period. Further investigation is needed to understand the mechanism through which exercise interventions improve clinical outcomes and which subgroup of patients will gain the most benefit.
P-OGC47 Anastomotic stricture after Ivor Lewis Oesophagectomy - An evaluation of incidence, risk factors and treatment
Authors: Koshy Renol , Brown Joshua , Chmelo Jakub , Watkinson Thomas , Prasad Pooja , Phillips Alexander 
Published: December 2021

Abstract

Background
Anastomotic stricture is a recognised complication after oesophagectomy. It can impact the patient’s quality of life and may require recurrent dilatations. The aim of this study was to evaluate the frequency of benign strictures, contributing factors, and the long-term outcomes of management in patients undergoing oesophagectomy with thoracic anastomosis using a standardised circular stapler technique.

Methods
All patients who underwent a two-stage transthoracic oesophagectomy with curative intent between January 2010 and December 2019 at this single, high volume centre were included. All patients who underwent a stapled (circular) intrathoracic anastomosis using gastric conduits were included. Those with variations to anastomotic technique or those not having a transthoracic anastomosis were excluded to reduce heterogeneity. Patients who developed malignant anastomotic strictures and patients who died in hospital were excluded from the analysis. Benign stricture incidence, number of dilatations to resolve strictures, and refractory stricture rate were recorded and analysed.

Results
Overall, 705 patients were included with 192 (27.2%) developing benign strictures. Refractory strictures occurred in 38 patients (5.4%). One, two, and three dilatations were needed for resolution of symptoms in 46 (37.4%), 23 (18.7%), and 20 (16.3%) patients respectively. Multivariable analysis identified the occurrence of an anastomotic leak (OR 1.906, 95% CI 1.088-3.341, p = 0.024) and circular stapler size &lt;28mm (OR 1.462, 95% CI 1.033-2.070, p = 0.032) as independent predictors of stricture occurrence. Patients with anastomotic leaks were more likely to develop refractory strictures (13.1% vs. 4.7%, OR 3.089, 95% CI 1.349-7.077, p = 0.008).

Conclusions
This study highlights that nearly 30% of patients having a circular stapled anastomosis will require dilatation after surgery for a benign anastomotic stricture. Although the majority will completely resolve after 2 dilatations, 5% will have longer-term problems with refractory strictures. Smaller circular stapler size and anastomotic leak have been identified as independent risk factors for developing a benign anastomotic stricture following oesophagectomy, and these patients should be monitored closely for symptomatology following surgery.
P-OGC63 Care Close to Home in the Era of Centralisation
Authors: Porritt Louise , Menon Ashok , Bharucha Shameena , Piercy Jennifer , Waterhouse Chloe 
Published: December 2021

Abstract

Background
With increasingly centralised services for people diagnosed with OG Cancer we wanted to ensure our local service was maintained to provide the appropriate care and management by collaborating with the Specialist Sites and raising the profile of local services. Most patients remain local due to their disease stage, performance status or through choice. We wanted those patients who have tests and treatment on other sites to be able to have their care managed locally as much as possible and therefore only have to travel when absolutely necessary. We aim to facilitate and deliver a streamlined service.

Methods
Weekly Local MDT triages patients to Specialist MDT once appropriate information is available.
Established local outreach clinic for specialist service. Ensures patients are known to specialist service from diagnosis. Patients will be diagnosed and managed locally unless input required elsewhere.
Local CNS attends both Local/Specialist MDT as patient advocate and provides cross site communication and care planning.
Local User Involvement- contributes to service development and feedback both locally and beyond.
Local HNA at point of diagnosis to establish a bench mark. Ongoing emotional support is integral to the local service and continues wherever the patient is in their care pathway.

Results
Streamlined care with local and specialist team contacts. Improved communication between professionals. Identifiable contact for patients
Rapid referral process - timely and appropriate discussions.
Improved patient satisfaction. Direct access to specialist site from point of diagnosis.
Improved patient advocacy across sites
Effective use of clinic time. The right patient being seen at the right time in the right hospital with the right information.
Local follow up enables integration of additional local services/teams into patient care
More inclusion for local teams in wider service development.
Local leadership within the network has ensured investment in local services and raised the profile.

Conclusions
Care is more streamlined
Patients are assessed by the right person at the right time enabling more open communication
Avoids unnecessary referrals
Less travelling between sites
Reduces patient anxiety
Encourages user involvement- more personalised care.
Promotes continuity of patient care
Allows inclusion of local teams in decision making at specialist level
Promotes collaboration and team working with flexible leadership amongst team members
Improved job satisfaction by establishing a shared vision
Upper GI Cancer delivery will continue to go through changes but with a motivated team who work together these changes can be implemented efficiently and effectively.
P-OGC69 Incidence, presentation and long-term sequelae of hiatus hernia after oesophagectomy: a 10-year retrospective cohort study
Authors: Chien Siobhan , Gall Lewis , Donnelly Paul , Dreyer Stephan , Khan Khurram , MacKay Colin , Macdonald Andrew , Craig Carol , Forshaw Matthew 
Published: December 2021

Abstract

Background
Hiatus hernia after oesophagectomy is a rare but recognised event, with potentially life-threatening consequences when there is bowel compromise. This 10-year retrospective cohort study aimed to identify the incidence and evaluate the clinical presentation and long-term management of hiatus hernia after oesophagectomy.

Methods
We conducted a retrospective analysis of all oesophagectomies performed in a single tertiary centre over a 10-year study period between 2010 and 2019. Demographics, details of the initial procedure and long-term outcomes were analysed. Patients that underwent post-operative computed tomography (CT) imaging at ≥ 12 months post-operatively were included in analysis, with all CT scans independently reviewed by a radiologist.

Results
212 patients were eligible for analysis. 25% (53/212) of patients developed a hiatus hernia post oesophagectomy. Demographic data were similar between patients who developed a hernia compared to those who did not. 75.5% (40/53) of post-operative hiatus hernias developed after transhiatal oesophagectomy (p &lt; 0.001), and patients with post-operative hiatus hernia had a higher BMI (p = 0.009); this association was confirmed on multivariate analysis. Hiatus hernia was frequently under-reported, with only 58.5% (31/53) mentioned on the formal CT report. 81.1% of patients (43/53) were asymptomatic. Operative intervention was only performed in 1 patient presenting with small bowel obstruction as an emergency.

Conclusions
Hiatus hernia is a potentially clinically significant and under recognised long-term complication following oesophagectomy, with a significantly higher incidence following transhiatal oesophagectomy and in obese patients. With increasing long-term survival after surgical resection and its preponderance to be found incidentally on cross-sectional imaging, judicious screening for hiatus hernia is warranted to prevent fatal complications.
P-OGC79 Post-operative NUn score as a prognostic tool for anastomotic leak after Oesophagectomy
Authors: Cheang Catherine Jenn Yi , Nair Gopikrishnan S , Patil Pradeep 
Published: December 2021

Abstract

Background
Anastomotic leak (AL) after esophagectomy is still quite high with incidence reported between 5 and 20%. Early detection of AL will enable patient rescue and the remedial measures may decrease the associated significant morbidity and improve quality of life. Oesophagectomy is also associated with other infective complications such as respiratory infections and collections in the abdomen or chest. Noble and Underwood (NUn) published the NUn score combining blood-borne markers of systemic inflammatory response to define risk of anastomotic leak and major complications following oesophageal resection. This study aims to validate the ability of NUn score to identify AL specifically.

Methods
A total of 113 patients who underwent esophagectomy for oesophageal cancer over 11 years from 2011 to early 2021 in our centre were selected for this study from a prospectively maintained database. Patients with leaks (n = 11) were identified by reviewing their case records, electronic records, endoscopy and radiological results. Patients with missing values were excluded. Postoperative 7-day (POD) biochemical data that included white cell count (WCC), C-reactive protein (CRP) and Albumin were used to calculate NUn score. Sensitivity and Specificity of NUn score with a cut-off value of &gt; 10 was calculated using the ROC curve analysis using SPSS.

Results
A total of 99 patients were included, among which 10 patients had anastomotic leaks (AL). Overall mean of NUn of patients with AL was 10.25 vs 9.95 without AL. NUn scores for day 1 to 7 are shown in the table in figure 1. NUn with the highest AUC was Day 7 (0.664 [CI 0.499 – 0.829]; p = 0.09), with 70% sensitivity and 57.3% specificity. The trends in WCC, CRP and albumin levels over 7 days were also not helpful in differentiating patients with AL.

Conclusions
In this study, the trends in rising WCC, CRP and decreasing albumin were not helpful in diagnosing anastomotic leaks specifically. The NUn score had a sensitivity of 70% on day 7. Procalcitonin, blood urea nitrogen or interleukin levels may help, and further studies are being planned. This study shows that current biochemical parameters can complement but not replace careful and regular medical examination and early radiological or endoscopic evaluation if an AL is suspected.