bluuebunny/crossref_metadata_2025_split huggingface dataset:
P22 Postoperative and pathological outcomes of CROSS and FLOT as neo-adjuvant therapy for oesophageal and junctional adenocarcinoma: an international cohort study from the Oesophagogastric Anastomosis Audit (OGAA)
Authors:   Oesophago-Gastric Anastomotic Audit (OGAA) Collaborative
Published: November 2022

Abstract

Introduction
Ongoing debate exists around optimum approach to locally advanced esophageal adenocarcinoma (EAC), with proponents for perioperative chemotherapy, such as FLOT, or multimodal therapy, in particular the CROSS regimen. This study aimed to compare the postoperative and pathological outcomes between CROSS and FLOT in esophageal adenocarcinoma (EAC) patients from an international, multicenter cohort.

Methods
Patients undergoing CROSS (n=350) and FLOT (n=368), followed by curative esophagectomy for EAC were identified from the Oesophagogastric Anastomosis Audit (OGAA).

Results
The 90-day mortality was higher after CROSS than FLOT (5% vs 1%, p=0.005), even on adjusted analyses (odds ratio (OR): 3.97, CI95%: 1.34–13.67). Postoperative mortality in CROSS were related to higher pulmonary (74% vs 60%) and cardiac complications (42% vs 20%) compared to FLOT. CROSS was associated with higher pCR rates (18% vs 10%, p=0.004) and margin-negative resections (93% vs 76%, p&lt;0.001) compared with FLOT. On adjusted analyses, CROSS was associated with higher pCR rates (OR: 2.05, CI95%: 1.26–3.34) and margin-negative resections (OR: 4.55, CI95%: 2.70–7.69) compared to FLOT.

Conclusion
This study provides real-world data CROSS was associated with higher 90-day mortality than FLOT, related to cardio-pulmonary complications with CROSS. These warrant a further review into causes and mechanisms in selected patients, and at minimum suggest the need for strict radiation therapy quality assurance. Research into impact of higher pCR rates and R0 resections with CROSS compared to FLOT on long term survival is needed.
O001 SARS-CoV-2 pandemic has impacted on patterns of aetiology for acute pancreatitis and management of gallstone pancreatitis in the United Kingdom
Authors: Spiers HVM , Nayar M , Pandanaboyana S 
Published: November 2022

Abstract

Introduction
The impact of the SARS-CoV-2 pandemic on patterns of aetiology of acute pancreatitis (AP) and management of AP in the UK is unknown.

Methods
A prospective multicentre cohort study of consecutive patients admitted with AP between 01/03/2020 and 23/07/2020 was undertaken. Patients were followed up for 12 months.

Results
1628 patients presenting with AP were included in the analysis. Gallstones (GSP) were the predominant aetiology (43.6%), followed by alcohol associated (25.8) and idiopathic (21.5%) AP. After completing aetiological investigations, 14.4% of the idiopathic cohort remained to have an idiopathic aetiology. 113/187 patients were readmitted during the ‘second wave’ of SARS-CoV-2 pandemic (after September 2020) with predominantly alcohol-related AP aetiology (49, 43.3%). Patients readmitted during the ‘second wave’, more commonly had alcoholic AP compared to the index cohort (43.4% vs 23.5% respectively; p&lt;0.001); however, there were no significant differences in AP severity (p=0.268). Of the 1358 patients with complete follow-up data, 620 (45.7%) presented with GSP of which only 66 (10.6%) underwent index cholecystectomy and 108 (17.4%) had an interval cholecystectomy with median waiting time of 32 days (IQR 16–56). Accounting for 44/456 patients with previous cholecystectomies, and 24 patients deemed unfit for cholecystectomy, the remaining 388 (77.3%) were still awaiting cholecystectomy at the end of 12 months.

Conclusion
The patterns of aetiology for AP changed during the SARS-CoV-2 pandemic with an increase in alcohol associated AP. Most significantly, access to cholecystectomy was restricted during the pandemic and readmission to hospital may have been driven by the need for cholecystectomy.

Take-home message
The patterns of aetiology for AP changed during the SARS-CoV-2 pandemic with an increase in alcohol associated AP. Most significantly, access to cholecystectomy was restricted during the pandemic and readmission to hospital may have been driven by the need for cholecystectomy.
O003 Radiation-related chromosomal aberrations observed in high volume endovascular operators performing X-ray guided surgery
Authors: Abdelhalim MA , Patel A , Moquet J , Smith A , Badie C , Anderson R , Ainsbury E , Modarai B 
Published: November 2022

Abstract

Introduction
The biological effects of chronic, low dose radiation, to which operators performing fluoroscopy-guided procedures are exposed, are unknown. We have previously demonstrated acute DNA damage/repair in lymphocytes from operators performing fluoroscopy-guided endovascular aneurysm repair (EVAR), but these markers normalised after 24 hours and did not inform on the residual accumulated effects of chronic radiation exposure. In the present study cytogenetic techniques were used to examine for chromosomal aberrations in endovascular operators.

Methods
Peripheral blood lymphocytes were isolated from high volume endovascular operators performing EVAR and age-matched radiation naïve general surgeons as controls. Giemsa staining was used to visualise the full complement of chromosomes and all dicentrics, where 2 centromeres are present in a single chromosome, were identified. The genome was analysed for abnormal exchanges of genetic material between chromosomes using multiplex fluorescence in situ hybridisation (mFISH).

Results
Lymphocytes from 18 operators (12 exposed, 6 controls) were analysed. A higher frequency of dicentric chromosomes were found in exposed operators compared with controls (0.0011 vs 0.0004, respectively, P=0.002) after examining 54,000 lymphocytes. Twice as many complex chromosome rearrangements were seen in endovascular operators compared with controls (0.48% vs 0.24%). Aneuploidy, the abnormal loss of chromosomes, was more frequent in endovascular operators with a median difference of 0.35 per chromosome (P=0.004).

Conclusion
We have found a higher frequency of chromosomal aberrations in endovascular operators compared with radiation naïve colleagues. This justifies further individual biological profiling for genomic instability and personalised radiation risk assessment.

Take-home message
Radiation-related DNA damage occurs in endovascular operators despite current radiation protection measures. Biological dosimetry could be a useful tool, allowing personalised risk assessment.
O004 Blood group antigen removal of a human kidney using ex-vivo normothermic machine perfusion technology
Authors: MacMillan S , Hosgood SA , Nicholson ML 
Published: November 2022

Abstract

Introduction
A novel strategy to overcome the constraints of ABO compatibility in solid organ transplantation is the enzymatic removal of blood group antigens using an alpha-galactosidase enzyme from Bacteroides fragilis during ex-vivo normothermic machine perfusion (NMP).

Methods
Human kidneys rejected for transplantation and offered for research were used in this study which was approved by the National Research Ethics committee and Research and Development office (NRES: 15/NE/0408). Blood group antigen removal using the alpha-galactosidase enzyme GH110B from B. fragilis was first investigated on formalin-fixed paraffin-embedded (FFPE) cortex sections from human kidneys of blood group B (n=5). Immunofluorescence co-staining of the blood group B antigens (isolectin GSIB4) and vascular endothelium (CD-31) was completed. A human kidney of blood group B was then treated with 0.0025mg/ml of alpha-galactosidase during 6hrs of NMP using an acellular perfusate solution. Serial biopsies taken throughout perfusion were stained and analysed for antigen removal.

Results
Alpha-galactosidase treatment of FFPE sections at all concentrations examined (0.0013mg/ml 0.5mg/ml) caused significant reduction of the Pearson correlation coefficient for B antigen and CD-31 co-localisation compared to the untreated control (p&lt;0.001). Following NMP of the treated B kidney, the Pearson correlation coefficient dropped from 0.182±0.042 (pre-treatment level) to a minimum of 0.017±0.102 after 6hrs (p&lt;0.0001), indicating a near-complete loss of the blood group antigens.

Conclusion
This is the first example of the enzymatic removal of type B blood group antigens from a human kidney during NMP. This strategy may have the potential to increase the pool of ABO compatible donor kidneys for transplantation.

Take-home message
We have shown that an alpha-galactosidase enzyme added during ex-vivo normothermic machine perfusion can be used to enzymatically remove the blood group B antigens from human kidneys, providing the first example of whole organ conversion in humans. This strategy has the potential to massively increase the pool of ABO compatible donor kidneys for transplantation.
O008 Are donor paediatric pancreatic grafts a viable option for pancreas transplantation, even in an adult recipient?
Authors: Tinker RJ , Owen RV , Tiwari N , Wilson CH , White SA 
Published: November 2022

Abstract

Introduction
Very few studies have analysed the outcomes of paediatric pancreatic grafts for whole pancreas transplantation. These grafts represent an important resource for both paediatric and adult recipients. Smaller donor grafts may have an increased risk of thrombosis and potentially less chance of insulin independence due to reduced beta cell mass in larger recipients. The aim of this study was to analysis of the use of donor paediatric pancreatic grafts for whole pancreas transplants.

Methods
NHSBT registry data from 2003–2021 was obtained (n=2,998), those with missing data specifically pertaining to paediatric grafts were removed leaving a final cohort of 2,812. Age groups were categorized by school year (pre-school, infants, junior and high-school students) to best represent paediatric growth and milestones. Univariate survival analysis was performed using Kaplan Meier plots and multi-variate analysis with cox regression models.

Results
The majority of grafts utilized were from donors &gt;18 years old (n=2,402, 85.4%). 12.4% (n=350) were aged between 12–18 years, 1.45% (n=41) 8–11 years, 0.6% (n=17) 4–7 years and our smallest group aged &lt;4 years 0.07% (n=2). We accept numbers are small for the youngest cohorts but there were no statistically significant differences between the different age groups in terms of either graft survival at 1 year (p=0.707) or 3 years (p=0.129) or patient survival at 1 year (p=0.06) or at 3 years (p=0.30).

Conclusion
This study has shown comparable graft and patient outcomes after pancreas transplantation irrespective of donor age and may help facilitate improved rates of graft utilization.

Take-home message
Paediatric donors have very similar outcomes to adult donors. Here we provided evidence that paediatric transplants for the pancreas should be more widely utilised.
O012 The role of the anti-miR-135/Spock1 axis on metabolism and drug response in intestinal/colon tumour organoids
Authors: Nateri AS , Babaei-Jadidi R. , Kashfi H , Alelwani W , Bakhtiari A , Kattan SW , Mansouri OA , Mukherjee A , Lobo DN 
Published: November 2022

Abstract

Introduction
Little is known about the role of microRNAs (miRNAs) in rewiring the metabolism within tumours and adjacent non-tumour bearing normal tissue and their potential in cancer therapy. This study aimed to investigate the relationship between deregulated miRNAs and metabolic components in murine duodenal polyps and non-polyp-derived organoids (mPOs and mNPOs) from a double mutant Apc/Fbxw7 mouse model of intestinal/colorectal cancer (CRC).

Methods
We measured glucose consumption and lactate production, and analysed the expression of 373 miRNAs and 12 metabolic genes using qRT-PCR and Western blotting in mPOs and mNPOs. The overexpressed miRNAs systematically target metabolic genes explored by the TargetScan web server. Organoid viability was assessed using MTT and Sulforhodamine-B (SRB) colorimetric assays.

Results
The tumour and adjacent non-tumour organoids showed differential metabolic activity. mPOs showed elevated lactate and consumption of glucose in the medium. Murine Apc/Fbxw7 duodenal polyp-derived organoids mimicked colorectal cancer patient-derived organoids. Our findings revealed miR-135b might target Spock1. Upregulation of SPOCK1 correlated with advanced stages of CRCs. Knockdown of miR-135b decreased the expression level of SPOCK1, glucose consumption and lactic secretion in CRC patient-derived tumours organoids (CRC tPDOs). Increased SPOCK1 induced by miR-135b overexpression promoted the Warburg effect and consequently antitumour effect of 5-fluorouracil.

Conclusion
Combination with miR-135b antisense nucleotides may represent a novel strategy to sensitise CRC to the chemo-reagent based treatment.

Take-home message
Our data highlight the therapeutic potential of targeting miR-135/SPOCK1 to enhance the treatment of colorectal cancer.
O013 The increasing burden of the two-week wait colorectal cancer pathway within a single centre
Authors: Farkas N , O’Brien JW , Palyvos L , Maclean W , Benton S , Rockall T , Jourdan I 
Published: November 2022

Abstract

Introduction
Increasing demand has placed colorectal cancer (CRC) two-week wait (TWW) pathways under pressure. The primary aims of this paper are to review TWW referral numbers and CRC diagnoses within our centre over the past 3 years (before, during and in recovery from the COVID-19 pandemic) and compare outcomes to our previously published data (2009–18). This incorporates the introduction of FIT into our clinical practice.

Methods
TWW CRC referral data from 1st July 2018–31st July 2021 was analysed. Parameters assessed; monthly TWW referrals, CRC detection, % of TWW referrals seen &lt;14 days and investigations utilised. Data from January 2009 to 31 June 2018 was combined. Unpaired t-test was used to compare group means.

Results
TWW referrals have increased 360% from 2009 to 2020. The proportion of TWW referrals with CRC has decreased from 8.87% to 3.24% over this period, whilst the incidence of CRC remained static (mean 58.7 per annum). From 2009–18, TWW referrals=8921, CRC diagnoses=533, mean monthly CRC detection rate=4.7, ratio of referrals to CRC=16.7:1. From 2018–21, TWW referrals= 6523, CRC diagnoses=232, mean monthly CRC detection rate=6.3, ratio of referrals to CRC=28.4:1. There was a statistically significant difference in mean monthly referrals (p-value&lt;0.00001) between the two periods.

Conclusion
Despite ever-increasing TWW referral numbers, no significant change in CRC diagnoses has occurred. We find our service under ever-increasing strain. Additional strategies and guidance are required to help address this. Further studies evaluating FIT and repeat FIT in the symptomatic TWW cohort may have a role in generating such a consensus.

Take-home message
Two week wait colorectal cancer referrals have increased 360% in 12 years. Colorectal cancer detection rate remains static over this timeframe.
O015 Discharge oral nutritional supplements on outcomes after gastrointestinal surgery: a systematic review and meta-analysis
Authors: Rowley A , Adiamah A , Kushairi A , Lewis S , Lobo DN 
Published: November 2022

Abstract

Introduction
Malnutrition is a risk factor for adverse postoperative outcomes. This systematic review and meta-analysis aimed to evaluate the impact of post-discharge oral nutritional supplements (ONS) on outcomes in patients undergoing gastrointestinal surgery.

Methods
The Medline, Embase and Cochrane databases were searched for randomised controlled trials (RCTs) in patients undergoing gastrointestinal surgery who had received ONS for at least two weeks after discharge from hospital. The primary endpoint was weight change. The secondary endpoints included quality of life, total lymphocyte count, change in grip strength and body composition. Analysis was performed using RevMan5.4 software.

Results
Sixteen studies were included with 1789 participants (903 in intervention group and 886 controls). Pooling of results in a meta-analysis revealed that there was significantly less weight loss in patients taking ONS, when compared with controls: overall OR=-1.36 (CI -2.48 to -0.23), P=0.02. Albumin concentration was significantly higher in the ONS group [OR=0.11 (95% CI 0.06 to 0.16) I2=0%, P=0.45]. Total lymphocyte count was also higher in the ONS group [OR=200.75/ml (95% CI 75.53 to 325.98/ml), I2=0%, P=0.76]. However, post-discharge complications and quality of life did not differ between the two groups. Patient compliance was relatively poor across the studies and there was variability in the volume and composition of ONS.

Conclusion
Overall, there was a reduction of weight loss and an improvement in other nutritional markers in patients taking ONS. However, future RCTs with more consistent methodologies are needed to investigate the efficacy of different ONS types on different patient sub-populations.

Take-home message
Oral nutritional supplements may be considered as standard care for certain patients after gastrointestinal surgery.
O016 Antibiotics versus appendicectomy for uncomplicated acute appendicitis: an updated meta-analysis of randomised controlled trials
Authors: Herrod PJJ , Kwok AT , Lobo DN 
Published: November 2022

Abstract

Introduction
Previous meta-analyses of randomised controlled trials (RCTs) on patients with uncomplicated acute appendicitis have demonstrated reduced complication rates with primary antibiotic therapy when compared with appendicectomy. This aim of this systematic review and meta-analysis of RCTs was to provide an update of the efficacy of antibiotic therapy compared with appendicectomy in adult patients with uncomplicated acute appendicitis.

Methods
MEDLINE, EMBASE and CENTRAL databases were searched with no date or language restriction. Data on complications of treatment, treatment efficacy (defined in the antibiotic group as not undergoing appendicectomy at 1 year, versus surgery without complications or negative histology in the appendicectomy group), readmissions, and length of stay (LOS) were extracted.

Results
We included 8 RCTs involving 3203 participants (1613 antibiotics/1590 appendicectomy; 2041 males/1162 females). Antibiotics had a reduced treatment efficacy compared with primary appendicectomy (RR 0.75, 95% CI 0.63–0.89). There was no significant benefit of primary antibiotic treatment on complication rates (RR 0.66 95% CI 0.41–1.04). In total 1010/1613 (62.6%) patients had successful antibiotic treatment at 1 year. In the 5 studies which explicitly reported hospital re-admission as an outcome, primary antibiotic treatment had a six-fold increase in readmissions (RR 6.28 95% CI 2.87–13.74). There was no difference in index admission LOS [Mean Difference 0.15 days (95%CI -0.05–0.35)].

Conclusion
Primary antibiotic treatment for acute appendicitis is associated with a reduced treatment efficacy and a significant readmission rate, without any benefit on complications or LOS. Approximately 40% of patients initially treated with antibiotics will require surgery within 1 year.

Take-home message
Contrary to previous meta-analyses, the current study suggests that although primary antibiotic therapy may be tried for uncomplicated acute appendicitis in adults, it is not definitive treatment in the long term.
O017 The virtual surgical specialty series: a platform for undergraduate surgical exposure during the pandemic
Authors: Hinchcliffe Z , Remsudeen R 
Published: November 2022

Abstract

Introduction
COVID-19 drastically disrupted medical education, with large proportions of teaching now delivered virtually. It is often challenging to replace face-to-face clinical placements, reducing student exposure to different specialities. The Surgical Specialty Series was created to provide a holistic understanding of various sub-specialties while restrictions to surgical placements existed. This study aimed to investigate the efficacy of our series in improving exposure and interest to surgical careers during the pandemic.

Methods
The series was delivered between October-May 2020/21, covering seven surgical specialties. Each month, three webinars were delivered by surgeons (varying grades), focussing on career pathways, post-graduate teaching and undergraduate revision. All sessions were advertised using social media and delivered via Zoom using online teaching tools (polls, screen-sharing, surgical videos). A feedback form was distributed for data analysis.

Results
The series saw 1124 total attendees (38–107 per webinar): 29.2% were from the home university, 25.9% were from other UK-based institutions and 44.8% were from overseas. Overall, a 21.6% increase was observed in student interest to pursue a surgical career. Although 24.2% of attendees were unsure beforehand, 13.4% developed a surgical interest after. Interactive polls and videos were reported most useful and enjoyable in student learning.

Conclusion
The virtual series was an effective alternative to in-person clinical attachments in raising awareness and undergraduate interest in surgery, despite COVID-19. It was beneficial in widening access to quality medical education, particularly to students overseas. Successes of this series should be considered when shaping the future of undergraduate surgical education in the ongoing pandemic.

Take-home message
The online webinar series was an effective alternative to in-person clinical attachments, through increasing surgical interest amongst medical students. Successes of this series should be considered when shaping the future of undergraduate surgical education in the ongoing pandemic.
O019 Comparison of skin substitute materials for use in remote surgical skill education
Authors: Awad L , Langridge B , Jeon F , Bollen E , Butler P E.M. 
Published: November 2022

Abstract

Introduction
Simulation training is increasing in popularity within the medical field. It provides a safe, reproducible environment in which learners can build upon surgical skills. The current pandemic has reduced workplace opportunities for learning, with decreased theatre opportunities and a high volume of trainees seeking training. In order for realistic skill development synthetic substitute materials have a role in facilitating training of suturing, excision, local flaps and other skills. The aims of this review were to compare commercially available synthetic materials for use in remote surgical skill training.

Methods
8 commercially available skin substitutes were included in this review; felt, foam dressing, a generic silicone skin pad, Sigma Lance Basic, Sigma Lance Advanced, Sigma Lance Infinity, Suture Doctor, and Limbs & Things. A questionnaire was distributed to 30 medical students, surgical trainees and consultants consisting of 8 criteria pertaining to surgical skills and similarity to skin. Cutometry and durometry data was obtained and compared to skin on the face, arm and back of 3 healthy participants under the age of 30.

Results
Overall, felt had the poorest outcomes in all domains. Foam dressing was comparable to skin on the face, back and arm for both cutometry and durometry. Foam dressing was comparable to commercially available skin pad results in the questionnaire.

Conclusion
Foam dressings are comparable to commercially available skin pads in application of surgical skills, and are a cost-effective alternative to facilitate delivery of remote training of surgical trainees.

Take-home message
Foam dressings constitute an alternative, comparable and cost-effective synthetic material for remote surgical skill development, particularly suturing, excision and local flap design.