bluuebunny/crossref_metadata_2025_split huggingface dataset:
O4: A NOVEL BOWEL DISEASE MODEL: PHENOTYPIC DIVERSITY OF CONTROL VS FAP ORGANOIDS
Authors: Martin I , Wu Y , Patel R , Kalra P , K S Clark , von A Roon , Latchford A , Moore JG 
Published: April 2021

Abstract

Introduction
The lifetime risk of colorectal cancer in familial adenomatous polyposis (FAP) approaches 100%. In patients who have undergone prophylactic colectomy, duodenal cancer is 100-300 times more common than in the general population, and an important cause of death. We aimed to develop in vitro models of mucosal crypt-derived organoids from patients with FAP.

Method
Biopsies from apparent healthy duodenal mucosa of FAP patients undergoing upper gastrointestinal endoscopy or surgery yielded crypts that were immobilised in Matrigel Basement Membrane Matrix (Corning) and cultured in IntestiCult Organoid Growth Medium (StemCell Technologies) to generate organoids for further morphologic and immunocytochemistry analyses (Dako and Abcam antibodies).

Result
Duodenal crypt-derived organoids from one healthy volunteer formed ring structures (days 1 -2) that progressed to expected branched structures (days 4-7). FAP-derived organoids from 9 patients all generated organoids with aberrant morphologies. These organoids expressed markers of Paneth cells (lysozyme), proliferation (Ki-67), goblet cells (Muc-2) and the single cell layer of mucosal epithelium (CK18).

Conclusion
This is the first report of duodenal crypt-derived organoids generated from FAP patients. Aberrant organoid morphologies were observed in all 9 patients. Immunocytochemistry confirmed markers of duodenal epithelium, suggesting a promising in vitro model to study disease aetiology in FAP.

Take-home message
This is a step towards a personalised model of disease for patients with familial adenomatous polyposis.
O19: FROZEN GEL-PACKS REDUCE POST-OPERATIVE PAIN AND NARCOTIC USAGE IN PATIENTS UNDERGOING SURGERY FOR BREAST CANCER
Authors: Ravindhran B , AM Hema , Vijaykumar M 
Published: April 2021

Abstract

Introduction
Adequate post-operative analgesia is important for recovery, early rehabilitation and patient satisfaction. We aimed to prove that patients undergoing surgery for breast cancer who receive cryotherapy via frozen gel-packs in the immediate postoperative period would report lower pain, require lesser narcotics and pain medication.

Method
This prospective randomized study was conducted at our tertiary care referral centre in South India. The pre-operative characteristics, intra-operative variables and post-operative outcomes were compared between two sets of matched cases and controls. Cryotherapy was delivered via frozen gel-packs for 12 hours immediately following surgery. Pain relief was assessed with the visual analog pain scale(VAS). Comparisons between groups were measured by the chi-square test, Fischer's-exact test, Independent samples t-test or Mann-Whitney U test as appropriate.

Result
81 patients were included in the study( Study-group=41 and control-group=40). For the primary outcome, mean postoperative pain score on postoperative days(PODs) 1(5.13±0.648 vs. 4.44±.502; t (79) = 5.3; p&lt;0.001) and POD 5(4.1±0.9 vs. 3.29±.642; t (79)=3.26; p&lt;0.001) were significantly lower in the cryotherapy group. The overall post-operative narcotic requirement(morphine equivalence) was reduced in the cryotherapy group(61.32±9.4 vs 55.8±11; t(79) = 2.421; p=0.018). The overall paracetamol requirement(grams) was also reduced in the cryotherapy group(2.1±.38 vs 1.9±.36; t(79) = 2.66; p=0.009). No significant difference was seen in the NSAID use between the groups. The cryotherapy group also demonstrated earlier functional recovery and lesser shoulder and arm stiffness(p=0.015).

Conclusion
Cryotherapy is a simple, cost-effective adjuvant to standard postoperative pain management which reduces pain, narcotics and promotes early rehabilitation.

Take-home message
Ice packs are a simple, cost-effective adjuvant to standard postoperative pain management which reduces pain, narcotic use and promotes early rehabilitation.
O29: PREDICTING RESPONSE TO NEOADJUVANT THERAPY IN OESOPHAGEAL ADENOCARCINOMA PRE-TREATMENT BIOPSIES
Authors: Lloyd M , Izadi F , Rahman S , Walker R , Hayden A , Harrington J , Grace B , Horne J , Machado M , Underwood T 
Published: April 2021

Abstract

Aims
We currently cannot predict which patients with locally advanced oesophageal adenocarcinoma will be amongst the 15-20% to gain a clinically important response to neoadjuvant therapy (NAT). This pilot study aimed to identify differentially expressed genes from oesophageal adenocarcinoma pre-treatment biopsies between responders and non-responders to NAT and develop methodology for predicting response.

Method
Response to NAT was assessed pathologically using Tumour Regression Grading (TRG). Pre-treatment formalin-fixed paraffin embedded samples were analysed with two nuclease protection assays (EdgeSeq, HTG = Oncology Biomarker Panel (OBP) and Precision Immuno-Oncology Panel (PIP)). Sequencing was performed on the NextSeq500 (Illumina).

Result
Whilst there was no difference in pre-treatment characteristics, responders (TRG1-2, n=26) had significantly better post-treatment pathology and overall survival than non-responders (TRG4-5, n=30). Genes up-regulated in responders were involved in regulating cell cycling, whereas genes up-regulated in non-responders were involved in cytokine signalling and the immune response. Neuronal artificial network models could predict response to NAT with overall accuracy of 73% and 68% for the OBP and PIP, respectively, which is promising considering the small sample size. As no model will be 100% accurate, we developed a model that could take patient's views into consideration with an adjustable probability threshold for classification.

Conclusion
This pilot study informs a biologically sound hypothesis for the basis of response to NAT and suggests prediction from pre-treatment biopsies may be possible using EdgeSeq. We now aim to validate these results in a larger study to inform a bespoke classifier of response to enable delivery of precision therapy.

Take-home message
In oesophageal adenocarcinoma, responders and non-responders to neoadjuvant therapy have different expression profiles. Through using EdgeSeq in larger studies, we may be able to predict which patients will respond to treatment, allowing for delivery of precision therapy.
O34: WHO SHOULD BE FOLLOWING UP IN PATIENTS WITH PROSTATE CANCER USING PSAS?
Authors: Lami M , Jackson G 
Published: April 2021

Abstract

Introdution
Prostate cancer patients are usually followed up using serial PSA testing. NICE provides guidelines for PSA follow up however whether this should be in primary care or secondary care is ambiguous. Consequently, there is a concern that PSAs are being missed. The primary aim of this study was to understand whether PSAs were being missed.

Method
A retrospective study was carried out at Whitehill General Practice. Patients were identified using codes for prostate cancer through Egton Medical Information Systems (EMIS) software. Data for patients followed up with PSAs between 2015-2019 was collected manually from documentation. Chi-squared statistical testing was used.

Result
47 patients had prostate cancer follow up with repeat PSAs. 45% patients were followed up solely by primary care whilst 40% had primary care follow up directed by specialists.
7 patients were excluded from further analysis. 35% of patients had missed PSAs, of which 18% had no reason documented. Furthermore, 19% had missed PSAs with solely primary care follow up. The difference in missed PSAs between solely primary care follow up versus those directed regularly by specialists was not significant (chi-squared 0.0177, p&gt;0.05).

Conclusion
PSAs are being missed because of a lack of a recall system. An ‘out of hospital’ recall system through a local administrative hub would allow for follow up standardisation. Involving patients in their follow up care should also be considered. By placing the responsibility centrally rather than to individual clinicians provides multiple fail safes to reduce missed follow ups.

Take-home message
An ‘out of hospital’ recall system through a local administrative hub would allow for follow up standardisation. Involving patients in their follow up care needs to also be considered.
O59: USE OF DEXTRAN 40 FOLLOWING PANCREAS TRANSPLANT MAY REDUCE EARLY INFLAMMATION AND SIGNIFICANT BLEEDING COMPARED TO A HEPARIN-BASED PROTOCOL
Authors: Innes AH , Tingle SJ , Ibrahim I , Thompson E , Bates L , Manas D , White S , Wilson C 
Published: April 2021

Abstract

Introduction
Dextran 40 (D40) is a synthetic colloid with anticoagulant properties, which is commonly used instead of heparin following pancreas transplantation, however there is a lack of evidence over which is more effective. Graft thrombosis and pancreatitis, which may be mediated through micro or macrothrombosis within the graft, remain significant complications following pancreas transplantation. We hypothesised that D40 reduces inflammation through its antithrombotic pro-microcirculatory effects. We aimed to evaluate D40 compared to a heparin-based protocol by comparing post-operative complications and post-transplant levels of inflammation.

Method
Data were collected retrospectively for pancreas transplant patients between December 2009 and August 2018 – 26 patients had been treated with the pre-Dextran protocol and 37 had received D40. Post-operative complications and inflammatory markers (WCC, CRP and amylase) on post-operative days 1, 2, 3 and 7 were compared between the two groups. Potential confounders were also recorded.

Result
Patients in the D40 group had similar thrombosis rates but were less likely to have had substantial post-operative bleeding compared to the heparin-based protocol. The group who received D40 had significantly lower CRP and WCC on days 2, 3 and 7. The differences on days 3 and 7 remained when the results were adjusted for the significant confounders - cold ischaemic time and donor age.

Conclusion
D40 appears to be as effective as IV heparin at preventing graft thrombosis following pancreas transplant, and to confer a reduced risk of bleeding. It may also reduce post-operative inflammatory processes, leading to reduced graft pancreatitis.

Take-home message
Using Dextran 40 as an anticoagulant after pancreas transplantation is as effective as IV heparin at preventing graft thromboses and has a reduced risk of bleeding.
O60: SURGICAL SITE INFECTION AND ANTIMICROBIAL RESISTANCE FOLLOWING RESECTION AND RECONSTRUCTIVE SURGERY FOR ORAL CANCERS: ARE WE READY FOR THE SUPER BUGS?
Authors: Ravindhran B , AM Hema , Vijaykumar M 
Published: April 2021

Abstract

Introduction
Surgical site infection(SSI) is the most common complication occurring in 19 to 47% of patients undergoing surgery for oral cancers. This study aims to assess the predictive factors of SSIs and antibiotic resistance patterns in patients undergoing surgery for oral cancers.

Method
The Clinico-pathological data of all patients who underwent surgery for oral cancers at our centre between October 2014 and May 2019 were reviewed. The differences between groups were compared by using independent samples t-test or Mann-Whitney U test and categorical data were analysed by Pearson's chi-square test, Fisher's exact or continuity correction. ROC curve was plotted to find the cut-off levels for the various predictors of SSI, using the Youden's index method. A linear regression analysis was done to define the cause-effect relationship of categorical response variables with explanatory variables.

Result
Of the 135 patients in our cohort, 43 patients(31.2%) developed SSI.Univariate and multivariate analysis showed that Diabetes, BMI&gt;25 or &lt;18, Neutrophil-to-Lymphocyte Ratio(NLR)&gt;3.75, Platelet-to-Lymphocyte Ratio(PLR)&gt;137.5, neo-adjuvant chemotherapy or radiotherapy, prolonged operative duration and prolonged anaesthesia exposure may render patients more vulnerable to SSI. On regression analysis, a PLR&gt;137.5, NLR&gt;3.75 and BMI&gt;25 or &lt;18 were found to be highly predictive of SSI. The highly resistant organisms isolated were staphylococcus aureus and enterococcus species.

Conclusion
The identification of these risk factors in patients undergoing surgery for oral cancers can help in identification of patients who may be at a higher risk of developing SSI and therefore help in improving the overall outcome, especially in an LMIC setting.

Take-home message
Identification of risk factors for surgical site infections in patients could help in prompt management of SSI and can also help in reduction of overall morbidity. The awareness and prevention of antibiotic resistance is vital for good outcomes in reconstructive surgery.
O64: GENOMIC PROFILING USING CIRCULATING NUCLEIC ACIDS IN STAGE IV MELANOMA PATIENTS RECEIVING IMMUNOTHERAPY REVEALS A NOVEL GENE AMPLIFICATION LANDSCAPE AND ALLOWS FOR DETECTION OF ACTIONABLE GENE MUTATIONS
Authors: Ita M , Wang JH , O'Leary P , Nolan Y , Toulouse A , Heffron C , Power D , Redmond HP 
Published: April 2021

Abstract

Introduction
Serial monitoring for disease progression and therapeutic efficacy at the molecular level in metastatic melanoma is hampered by a lack of reliable blood borne biomarkers. Molecular profiling of melanoma tumours is almost impractical in metastatic disease due to risks of procedure related morbidity and sampling inefficiency in representing tumour heterogeneity. Cell free DNA allows monitoring of molecular changes in melanoma over the course of immunotherapy. We investigated the utility of somatic mutation and gene amplification analyses in melanoma patients receiving immunotherapy.

Method
Cell free DNA was extracted from plasma using a QIAamp Circulating Nucleic Acid Kit (Qiagen). Pathway focused profiling of somatic mutation status was performed by ARMs PCR using QBiomarker Somatic Mutation PCR Arrays (Qiagen). Gene amplification analysis was performed by Real Time Quantitative PCR (Roche) using RT2 Profiler PCR Arrays (Qiagen).

Result
A total of twenty patients with stage IV melanoma receiving immunotherapy were enrolled in this study. The BRAF p.V600E mutation was detected in the cfDNA of 80% of BRAF positive patients. Cell free DNA was also profiled for a total of 84 genes of the cancer inflammation and immunity pathway. There was a significant difference in the copy numbers of several genes (CTLA-4, CXCL12, CXCL5, IDO1, TGFB, IFNG, IL4, PTGS2, AICDA, HLA-A, CCL4, ACKR3, TP53, MYC) between patients with progressive disease and therapeutic response (n=20, p &lt; 0.05).

Conclusion
We postulate that cell free DNA pathway focused somatic mutation and gene amplification analyses may be useful in evaluating disease progression and therapeutic response.

Take-home message
Genomic analysis of circulating nucleic acids may be useful in evaluating disease progression and therapeutic response in metastatic melanoma.
O65: C-MET PROTEIN AS A COLORECTAL CANCER BIOMARKER FOR FLUORESCENCE IMAGE-GUIDED SURGERY
Authors: Armstrong G , Portal C , Khot MI , West NP , Maisey T , Perry S , Tolan D , Jayne DG 
Published: April 2021

Abstract

Introduction
The c-Met transmembrane protein is vital for cell differentiation and migration and is overexpressed in many gastrointestinal cancers. This study aimed to investigate a novel c-Met targeted peptide coupled to a fluorophore (EMI-137, Edinburgh Molecular Imaging Ltd.) for use in fluorescence image-guided colorectal cancer (CRC) surgery.

Method
A high c-Met expressing cell-line, HT29, was identified with temporary RNA suppression and used to develop a mouse xenograph CRC model. Tumours were allowed to grow to 10mm. EMI-137 was injected into the tail vein and biodistribution analysed using the IVIS system.
Nine patients undergoing elective surgery for colon cancer received a single IV dose EMI-137 1-3 hours before surgery. Tumour and LN fluorescence was assessed with a prototype Karl Storz laparoscope. Intraoperative fluorescence was correlated with radiological and pathological TNM stage and tissue c-Met expression using immunohistochemistry.

Result
The HT29 xenograph CRC model demonstrated selective EMI-137 uptake and fluorescence 1- 6 hours post administration. Nine participants aged 67-77 years received EMI-137 106 minutes (S.D±17) before surgery. Marked background fluorescence was observed in all patients. 4/9 (44%) patients showed mild increase in tumour fluorescence over background. 5/9 patients had histological LN disease, but no fluorescent nodes were detected intraoperatively. There was no correlation with T-stage. At histopathological assessment 8/9 participants showed moderate or high tumour c-Met expression. 8/8 malignant LNs demonstrated high c-Met expression.

Conclusion
EMI-137 is specific for human c-Met in 2D and xenograph CRC models. EMI-137 is safe for human use but its utility is limited by insufficient tumour-to-background ratios.

Take-home message
This first-in-man study of a novel fluorescent peptide targeted to the c-Met receptor, found EMI-137 lacked the sensitivity and specificity to accurately map the tumour margins and lymph node burden in laparoscopic colonic cancer resection surgery.
O67: PERFUSATE GLUCOSE REFLECTS TISSUE GLYCOGENATION DURING LIVER PERFUSION
Authors: Matthews L , Irwin E , Ezuma P , Ibrahim I , Bates L , Thompson E , Wright M , Figueiredo R , Bury Y , Wilson C 
Published: April 2021

Abstract

Introduction
Normothermic machine perfusion (NMP) is a method of organ preservation that aims to replicate the physiological environment, achieved by perfusing the livers with a blood-based perfusate at physiological inflow pressures and temperature. NMP also permits viability assessment through evaluation of the perfusate flow rates through the portal vein and hepatic artery. In addition to this, biochemical assessment and perfusate gas analysis can be performed to provide insights into the metabolic activity of the liver.

Method
Discarded human liver grafts (n=6), were perfused for 24 hours. Core biopsies and perfusate samples were taken from each liver at 5 distinct time intervals over 24 hours. Core biopsies were fixed and stained with periodic acid-Schiff and analysed with Leica software to provide a quantitative estimate of the hepatocellular glycogen content.

Result
Hepatic glycogen concentration rose during the first hour, followed by a steady decline thereafter until the end of perfusion. Contrary to our initial hypothesis that glucose concentration within the circuit would show an inverse relationship to glycogen stores in the liver cells, we found that glucose concentration closely followed the same trend.

Conclusion
Change in hepatocyte glycogen content provides an important insight into the synthetic function of a liver destined for transplant. Our research suggests that glucose concentration can be used as a surrogate marker for the synthetic function of a liver on NMP and provides valuable information on the glycogen-synthesising capability of the hepatocytes. In future, this could potentially aid the decision-making process with regards to liver graft transplant viability.

Take-home message
Perfusate glucose concentration could provide an insight into the viability of liver transplants
P10: LYMPH NODE YIELD IS NOT A RELIABLE PROGNOSTIC MARKER IN ANTERIOR RESECTION AND ABDOMINOPERINEAL RESECTION FOLLOWING NEOADJUVANT THERAPY FOR RECTAL CANCER
Authors: Harris J , Fleming CA , Ullah MF , McNamara E , Murphy S , Shelly M , Waldron D , Condon E , Coffey JC , Peirce CB 
Published: April 2021

Abstract

Introduction
International guidelines recommend a minimum lymph node yield (LNY) of ≥12 for oncological resection in colorectal cancer (CRC). Neoadjuvant chemoradiotherapy (NACRT) decreases LNY, which questions its ability to provide accurate prognostic information. The consensus of this significance remains undetermined. This study aimed to investigate the significance of LNY on recurrence and survival following anterior resection and abdominoperineal resection with or without NACRT for rectal cancer.

Method
Prospectively collected data on patients diagnosed with rectal cancer in a tertiary referral centre was interrogated retrospectively. Patients were divided into primary surgery and NACRT groups. Univariable analysis was performed using Fisher's exact test, t-test, and x2 test, while multivariable analysis utilised a multiple regression model. Disease recurrence and survival was analysed with logrank test for Kaplan-Meier curves.

Result
148 patients were included [56.1% (n=83) receiving NACRT]. The median LNY of the primary surgery group was 14 [interquartile range (IQR) 11-19] and for the NACRT group was 12 (IQR 8-14) (p &lt;0.001). Disease recurrence was similar in both primary surgery and NACRT groups. There was a significant decrease in overall mortality in NACRT patients (p = 0.03), but there was no significant difference observed in recurrence or mortality amongst LNYs of &lt;8, 8-11, and ≥12.

Conclusion
LNY less than 12 was not a negative prognostic indicator following NACRT and surgery for rectal cancer.

Take-home message
A lymph node yield of less than 12 is not a negative prognostic indicator in rectal cancer patients who receive neoadjuvant chemotherapy.
P16: PHYSICAL THERAPIES FOR DVT PROPHYLAXIS IN SURGICAL PATIENTS: A SYSTEMATIC REVIEW AND EVIDENCE QUALITY APPRAISAL
Authors: Berner JE , Geoghegan L , Kyriazidis I , Nanchahal J , Jain A 
Published: April 2021

Abstract

Introduction
Venous thromboembolism represents a significant clinical and socioeconomic burden. Surgical patients are an inherently high-risk cohort for VTE although traditional prophylactic pharmacological therapies are contraindicated in select cohorts. Novel physical therapies such as calf exercises and electrostimulation have been proposed for such patients. The aim of this systematic review is to appraise the clinical utility of novel physical therapies used for DVT prophylaxis in surgical and trauma patients.

Method
A systematic review of MEDLINE, EMBASE and CINAHL using a PRISMA-compliant methodology up to July 2019 was conducted. Abstract screening and data extraction were performed in duplicate. Risk of bias and quality assessments were performed for each study using the GRADE framework.

Result
A total of 272 articles were identified, of which 10 met inclusion criteria. Five studies evaluated the use of calf electrostimulation, the remaining studies evaluated active toe movement, bespoke compression bandages, blood flow restriction exercises, calf massage and a portable compression device. Four randomized controlled trials demonstrated a significant reduction in radiological DVT incidence with electrostimulation, post-operative massage and pneumatic compression versus controls. All included studies had a moderate to high risk of bias.

Conclusion
The role of physical therapies as prophylactic measures in VTE remain equivocal. No study demonstrated a significant reduction in clinically evident DVT. The physical therapies can be beneficial in patients who also received pharmacological therapy, whilst physical therapies alone may be of no benefit. Heterogenous study design and poor methodological quality limit comparison of study findings at present.

Take-home message
Physical therapies as prophylactic measures in venous thromboembolism may offer benefit when combined with pharmacotherapy. When used alone, physical therapies may offer no benefit.