bluuebunny/crossref_metadata_2025 huggingface dataset:
O014 SIKs suppress tumourigenesis in colorectal cancer and can serve as prognostic biomarkers
Authors: Alcazaren L , Martin T , Jiang W , Ruge F
Published: May 2023

Introduction

Salt inducible kinases (SIKs) have a role in various biological process, including tumourigenesis in a tissue-dependent manner. However, their role in colorectal cancer (CRC) has yet to be established. We hypothesise that SIKs are differentially expressed in CRC, both promoting and preventing tumourigenesis.

Methods

SIK mRNA expression was determined within the Cardiff CRC cohort using reverse transcription-quantitative PCR and clinicopathological features were evaluated. Kaplan-Meier survival curves were created. SIK protein expression in CRC tissue were analysed using immunohistochemistry. SIK knockdown (KD) models were created to investigate the role of SIKs on barrier function and migration in vitro.

Results

Low SIK levels within CRC tissue were associated with poorer clinicopathological features. At the protein level, SIKs were downregulated in CRC tissue. Reduced expression of SIK2 and SIK3 were linked to poorly differentiated tumours. SIK KD induced different effects on cell barrier function, depending on the cell type. SIK KD increased cell migration in HT115 cells but reduced it in HRT18 cells.

Conclusion

Following translation, SIK expression was lower in CRC tumours than in normal tissue. Low SIK levels correlated to poorer clinicopathological characteristics, demonstrating their protective role in CRC. SIK loss contributed to cell-cell barrier dysregulation in vitro, revealing a possible mechanism of how SIKs regulate the metastatic potential of tumours. We demonstrate for the first time, the expression and role of all three SIKs in the tumourigenesis of CRC. This novel discovery has revealed possible therapeutic targets and biomarkers.
O015 CD34+ vascular stem cells play a key role in vein graft remodelling
Authors: Xu S , Smith A , Modarai B
Published: May 2023

Introduction

Venous conduits that are grafted into arterial circulation undergo neointima remodelling, causing excessive hyperplasia that contributes to early graft failure which a major drawback of surgical vein grafting. Stem cells expressing the CD34 surface protein have been postulated to have a key role in the process, but their involvement has not been studied.

Methods

A segment of the inferior vena cava of wild-type mice was interposition grafted into mice in which CD34-expressing cells were located through their genetically induced expression of tdTomato red marker protein (CD34-CreERT2xRosa26-tdTomato mice). This enabled us to determine whether CD34+ derived cells found in the vein after grafting originated from the donor mouse or from the host. Grafts were explanted 4wks after surgery and analysed by immunohistology and single cell RNA sequencing to resolve cell-level gene expression. Cells from vein grafts were also cultured in vitro and proliferation/differentiation assays were carried out on purified CD34+ cells.

Results

70% of cells in the vein graft neointima were derived from CD34+ graft lineage whereas there was no significant contribution of recipient-derived stem cells or bone marrow cells to the neointima. Vein graft neointima smooth muscle cells (SMC) are not stem cells derived. CD34+ stem cells differentiated predominantly into fibroblasts which induced vein SMC phenotype switching and proliferation.

Conclusion

The majority of CD34+ stem cells found in the neointima of veins, grafted into the arterial circulation were derived from the resident cell population. These cells
O036 Postoperative complications are predicted by surgery duration in the unilateral deep inferior epigastric perforator (DIEP) flap reconstruction: a retrospective cohort study
Authors: Shtarbanov P , Ioannidi L , Ghali S , Hamilton S , Ahmed Z , Nikkhah D
Published: May 2023

Introduction

Currently, one published study documented operative time (OT) as a predictor for postoperative outcomes in bilateral deep inferior epigastric perforator (DIEP) flap breast reconstructions. No literature has investigated this in unilateral DIEP flaps. We aimed to determine the relationship between unilateral OT, postoperative complications and length-of-stay (LOS).

Methods

Electronic hospital data of adult women that underwent elective immediate or delayed unilateral DIEP reconstruction at a tertiary centre in London, between 2021 to 2022, was retrospectively analysed. Patients were divided into four groups depending on OT quartiles to define a critical cut-off period. Data on extensive potential confounders was recorded and used in univariable and multivariable regression models. Further statistical analyses were performed where appropriate.

Results

The final cohort contained 66 patients. Through quartiles, the risk-adjusted cut-off OT was defined as 515 minutes. After risk-adjustment, operations >515 minutes had a significantly higher overall complication rate than ≤515 minutes (HR: 2.16, p=0.032, 95% CI: 1.067, 4.38). No significant difference in mean ranks of LOS (p=0.16) was noted above the cut-off period. In patients that developed at least one complication type, no significant difference was observed in the unadjusted return-to-theatre rate between the two groups (HR: 0.86, p=0.82, 95% CI: 0.23, 3.24).

Conclusion

We confirmed OT was an independent predictor for postoperative complications in the DIEP flap and demonstrated this in unilateral reconstructions. Larger multicentre prospective studies are required to ascertain the significance of the OT effects, and to deduce the minimum OT threshold below which detriment to patient outcomes arises.
O037 VEGF-A: a potential prognostic biomarker for donor liver viability
Authors: Cheemungtoo G , Dobbins J , Mahendran B , Tingle S , Bates L , Figueiredo R , Amer A , Sen G , Hammond J , Talbot D , White S , Manas D , Wilson C
Published: May 2023

Introduction

Waitlist mortality for liver transplant recipients may be tackled by increasing graft utilisation from marginal donors. At present, there are no reliable methods of assessing the quality of potential donor grafts prior to post-transplantation complications such as early allograft dysfunction (EAD). This pilot study evaluates the validity of a patented biomarker panel on flush effluent samples collected on the backbench after organ retrieval.

Methods

All flush effluent samples were collected and stored with patient consent and ethical approval. Flush effluents were retrieved from cold-stored donor liver grafts on the backbench for both transplantation and research purposes. Meso Scale Diagnostics multiplex assays were used to quantify biomarker levels in each sample with a BCA protein assay for data normalisation. Graft utilisation was assessed as our primary outcome measure and post-operative EAD incidence was our secondary outcome.

Results

Thirteen donor livers were sampled, out of which 61.5% (n=8) were transplanted and 38.5% (n=5) were declined. Utilisation outcomes analysis demonstrated that only VEGF-A levels were significantly different between the transplanted and declined grafts (p<0.001). EAD incidence was 37.5% (n=3) from the 8 transplant recipients. There was no statistical significance between each biomarker level and the development of EAD post-transplantation.

Conclusion

Liver flush effluents are a rich, novel source of protein biomarkers. Flush VEGF-A may be a prognostic biomarker for donor liver viability. Further evaluation is warranted for point of care testing.
O042 Enzymatic conversion of human blood group A kidneys to universal blood group O
Authors: MacMillan S , Hosgood S , Rahfeld P , Kizhakkedathu J , Macdonald S , Withers S , Nicholson M L
Published: May 2023

Introduction

The ABO blood group restriction on allocation of donor organs leads to waiting time disadvantages for individuals of more restrictive blood types. Here, we outline the first preclinical use of two enzymes from Flavonifractor plautii to convert human blood group A kidneys to universal blood group O.

Methods

Six pairs of human kidneys rejected for transplantation and offered for research were used to in this study with approval from the National Research Ethics committee and Research and Development Office (NRES: 15/NE/0408). Three pairs were perfused for 6 h using normothermic machine perfusion (NMP), and three pairs were perfused for 24 h using hypothermic machine perfusion (HMP), with one kidney per pair randomised to enzyme treatment. Cortical biopsies collected throughout perfusion were examined for antigen loss using immunofluorescence microscopy.

Results

After 2hrs of NMP, a significant loss of 83.4±10.2% blood group A antigen expression was observed compared to pre-treatment levels (p=0.012), while no significant changes were observed in control kidneys (p=0.999). For HMP, a maximal loss of 71.2±21.9% was observed after 6 h (p=0.066), with no decrease observed in the contralateral controls (p=0.977). Haemodynamic perfusion parameters were stable in both cohorts, with no significant difference between control vs treated kidneys.

Conclusion

Our results show a loss of 70-80% of blood group A antigens in as little as 2 h of NMP and 6 h of HMP. These approaches pave the way for the first clinical studies that could herald the start of a new era that transforms donor organ allocation in kidney transplantation.
O051 Combining sarcopenia and asa status to inform emergency laparotomy outcomes: could it be that simple?
Authors: Karolewski J , Ming Y J , Howley P , Holmes M , Gani J , Pockney P
Published: May 2023

Introduction

Emergency laparotomy mortality prediction tools are usually multipoint scoring systems such as NELA, ACS-NSQIP, and P-POSSUM. However, these tools are time consuming and complex to use. Sarcopenia on CT scans is correlated with mortality in emergency laparotomy patients and we explored the combination of this (as measured by PM:L3) with ASA as a simple and efficient tool to predict the outcome of Emergency Laparotomies.

Methods

A retrospective analysis was conducted across four hospitals, identifying 500 patients who underwent emergency laparotomies between 2016-2017 and had contemporaneous abdomino-pelvic CT scans. Radiological sarcopenia was measured using the PM:L3 ratio on a cross-sectional axial CT slice. PM:L3, NELA, ACS-NSQIP, and P-POSSUM, as well as simplified ASA (sASA) were retrospectively calculated and assessed as potential predictors of 30-, 90-, and 365-day mortality.

Results

ACS-NSQIP, NELA, P-POSSUM and PM:L3/sASA were each statistically significant predictors of 30-day, 90-day and 365-day mortality (p<0.001). Logistic regression models of 30-, 90- and 365-day mortality containing just the two predictors PM:L3 and simplified ASA exhibited AUCs of 0.838, 0.805 and 0.775 respectively, which are comparable with the best currently used predictors ACS-NSQIP and NELA.

Conclusion

Combining PM:L3 with ASA scores appears to be a significant predictor of 30-, 90-, and 365-day mortality in emergency laparotomy patients in Australia. The results are comparable with some of the best performing widely used risk assessment tools and provide a more time-efficient and accessible method of performing risk assessments in Emergency Laparotomy patients.
O052 Erect chest X-ray is inadequately diagnostic and falsely reassuring in assessment of abdominal visceral perforation: a retrospective cohort study
Authors: Saji A P , Shah J , Hajibandeh S , Hajibandeh S
Published: May 2023

Introduction

Pneumoperitoneum refers to air in the abdominal cavity due to abdominal visceral perforation and can be visualised as air under the diaphragm on erect chest x-ray. This study aims to evaluate the accuracy of erect CXR in detecting the presence of abdominal visceral perforation.

Methods

A retrospective cohort study in a single centre was conducted between January 2014 and January 2020. The study population comprised of all patients with gastrointestinal perforation confirmed by assessment during emergency laparotomy. The outcome measure of this study was perforation detection rate, defined as detection of air under diaphragm in preoperative erect CXR confirmed by two independent qualified radiologists.

Results

A total of 219 patients were eligible for inclusion in this study. Among 219 patients with intraoperative evidence of abdominal visceral perforation, preoperative erect CXR showed air under diaphragm in 43 patients. The perforation detection rate was 20% (95% CI 15-26%). Subgroup analysis based on the level of perforation showed that the perforation detection rate was 32% (95% CI 21-43%) in patients with upper gastrointestinal perforation and 13% (95% CI 8-20%) in patients with lower gastrointestinal perforation.

Conclusion

Erect CXR can only detect the presence of abdominal visceral perforation in 20% of patients and does not provide any information about the level or cause of perforation. The time is to move away from the use of erect CXR in assessment of patients with acute abdominal pain. It is inadequately diagnostic and falsely reassuring. All patients with suspected perforation should have immediate CT scan.
O054 Return to pre-hospital residence following emergency laparotomy
Authors: Rugendyke A , Holmes M , Ming Y , Gani J S , Pockney P
Published: May 2023

Introduction

Poor outcomes following emergency laparotomy include death and the loss of independent living. A widely-held apprehension is the ‘salvage’ of a previously independent patient, only to render them reliant on long-term dependent care. We aimed to establish the proportion of patients who returned to their pre-hospital residence following emergency laparotomy, measured at discharge, 90 and 365 days.

Methods

Data was collected on all patients over 18 years of age who underwent emergency laparotomy across four Australian hospitals between 1 January 2018 and 31 December 2019. Data recorded included pre-hospital residence, discharge destination, mortality and place of residence at 90 and 365 days.

Results

782 patients underwent an emergency laparotomy during the study period. The mean age was 64 years (range 18-96). Prior to hospital admission, 95.5% of patients lived in their own home, while the remainder resided in supported living facilities. 7% of patients died during their hospital admission. Of those alive on discharge, 77.6% were discharged to their pre-hospital residence. At 90 days, mortality was 10.6% while 97.1% of surviving patients had returned to their pre-hospital residence. By 365 days, mortality was 17.0% while 98.0% of surviving patients had returned to their pre-hospital residence, and 94.0% were living in their own home.

Conclusion

Patients who survive 90 and 365 days following emergency laparotomy nearly all return to their pre-hospital residence, with only a small proportion of previously independent patients entering dependent care. This should inform shared decision-making regarding emergency laparotomy in the acute setting.
O063 Should the presence of a carotid web be an indication for carotid intervention? A 12-year single centre retrospective study
Authors: Erete L , Islam S , Glasgow S , Baker D
Published: May 2023

Introduction

Carotid webs are a rare form of focal fibromuscular dysplasia and a possible cause of ischaemic stroke. They are defined as an abnormal shelf-like projection of intimal fibrous tissue into the carotid bulb. We reviewed patients found to have carotid webs at our unit over a 12-year period.

Methods

Radiology reports of all cross-sectional imaging from 2010-2021 were searched for the phrase carotid web. Images were reviewed to confirm the finding. Patients with previous carotid intervention were excluded. Electronic patient records were reviewed to establish presenting symptoms, diagnosis, management and stroke recurrence.

Results

60 patients with carotid webs were identified. Ages ranged from 36-92 years. The gender ratio was 31 male:29 female. 29 patients had left-sided carotid webs, 22 right-sided and 9 bilateral. No patients had a pre-event diagnosis of fibromuscular dysplasia. 27 patients had an ischaemic intracerebral event - 18 in the territory relevant to the web location and nine in other territories. 1 patient was treated with thrombolysis, 1 with thrombectomy and 1 with thrombolysis and thrombectomy. None underwent carotid intervention. Of the 18 patients with a carotid web on the ipsilateral side to their ischaemic event, none had a repeat event recorded.

Conclusion

30% of patients had an ischaemic event corresponding to the territory supplied by a carotid artery with a web. Current management of carotid webs favours conservative management with antiplatelet therapy. However, these data suggest carotid intervention should be considered in selected patients where stroke symptoms correlate to the laterality of the carotid web.
O068 Magnesium, the anaesthetists’ friend during carotid endarterectomy (CEA)
Authors: Myers A , Baker D , Adedugbe I
Published: May 2023

Introduction

Magnesium can be used as an antihypertensive for CEA patients, with the added benefit of anti-arrhythmic and anti-convulsive effects without the negative chronotropic effect of classic antihypertensives. It however causes vasodilation and increased diuresis, possibly increasing post-operative vasopressor requirements. This study determines the postoperative haemodynamic impact of magnesium therapy on CEA patients.

Methods

A retrospective review of CEA patients’ medical records between April 2020 and December 2021 was undertaken. In our unit, the postoperative trigger for commencing vasopressors (metaraminol or noradrenaline) is a systolic blood pressure <110 mmHg. A comparison of the postoperative vasopressor requirements in patients given intraoperative magnesium {5g IV infusion over 20 min if SBP >170mmHg} with those not given magnesium therapy was made (using Chi-square test). A secondary outcome was to assess the development of new acute postoperative kidney injury (AKI) (eGFR <60 ml/min/1.73m2).

Results

Of the 89 CEA patients; 8 had incomplete data and 65% were over 70 years old. The Surgical Outcome Risk Tool (SORT) score identified 44 (53%) patients as high risk (>5% risk of perioperative mortality). There was no difference between the magnesium vs non-magnesium therapy groups postoperatively in vasopressor requirement. (p=0.38, X2=0.74) or AKI rates (n=14, 16.8%).

Conclusion

Organ perfusion and cardiac stability can be achieved perioperatively in CEA patients with magnesium therapy without increasing vasopressors requirement or renal impairment; making it a good first-line therapy for intraoperative hypertension.
O072 A 6-year cohort study assessing outcomes following calf fasciotomies at a single tertiary vascular trauma centre
Authors: Gnanasundaram A , Laloo R , Bailey M , Scott D
Published: May 2023

Introduction

Acute compartment syndrome (ACS) is a surgical emergency. Delayed diagnosis and fasciotomy can result in irreversible muscle necrosis causing permanent disability and major amputation. This study compared outcomes following prophylactic (Group1) versus therapeutic calf fasciotomies (Group2), as well as early (within 6 hours) versus delayed fasciotomies (>6 hours) at a single tertiary vascular trauma centre.

Methods

All patients undergoing calf fasciotomies between 1st January 2017 and 31st November 2022 were identified from a prospectively collected vascular departmental database. The primary outcomes included foot drop, amputation and mortality while infection, wound debridement, neuropathic pain and negative-pressure dressing were secondary outcomes. Statistical analysis with SPSS was performed using Fisher's exact test.

Results

88 patients (65 men, 23 women) of median age (IQR) 67 (56-74) underwent calf fasciotomies. Of these, 43 (48.9%) were therapeutic (Median age=62) and 45 (51.1%) were prophylactic (Median age=67).Ischaemia was more prevalent among Group1 while trauma among Group2.There were no significant differences among outcomes between both groups apart from higher 30-day mortality rate (26.7% vs. 7.0%, p=0.014)and incidence of neuropathic pain (22.2% vs. 4.7%, p=0.027)in Group1 versus Group2.Most patients (79.5%) underwent early calf fasciotomy with no significant differences in primary and secondary outcomes between early and delayed fasciotomy groups. The delay was attributed to theatre unavailability (n=6) and on-going resuscitation (n=5).

Conclusion

Higher rates of neuropathic pain and 30-day mortality in group1 may be attributed to co-existing lower limb ischaemia. Further work is required to establish the impact of neuropathic pain. Pathways should be developed to ensure rapid access to theatres for patients with suspected ACS.
O080 Evaluation of patient post-operative outcomes after deep inferior epigastric perforator (DIEP) flap surgery
Authors: Shatskikh M , Coe L , McMahon M , Kennedy-Williams S , Hil A , Martin-Smith J
Published: May 2023

Introduction

The Deep Inferior Epigastric Perforator (DIEP) flap is considered the gold standard procedure for breast reconstruction. The long-term cosmetic outcomes of the reconstructed breast are unmatched by alternative reconstructive methods, however the donor site morbidity, including pain, scarring and extended recovery periods, require patients to consider their preferred option.

Methods

There is a paucity of data regarding return to pre-surgical activity timelines, and effect of reconstruction on psychosocial, sexual, and physical wellbeing. After obtaining audit approval, we utilized the Breast-QTM questionnaire to conduct a prospective cohort study. DIEP breast reconstruction patients in a tertiary referral, high-volume centre (N=26) were assessed prior to surgery and at 3 months post-operatively.

Results

An average of 20.3 days were lost to hospital admissions, follow-up, and post-operative recovery. Of employed patients, 68% had not yet returned to work. For those that did, an average of 6 weeks was required to feel well enough. Additionally, patients reported needing 4.8 weeks to drive again, 4.4 weeks to resume chores, 3.7 weeks to recommence childcare duties and 4.3 weeks to resume exercise. Comparing pre-operative and post-operative Rasch Transformed Scores, patients’ sexual wellbeing score decreased (58.3 to 52.2, p=0.09), while their psychosocial wellbeing score increased (62.1 to 66.7, p=0.16). Qualitatively, patients reported significant challenges impacting return to baseline, particularly involving abdominal scar site, size, and associated healing delays.

Conclusion

Ultimately, results of our work indicate the need for additional patient supports to improve outcomes, decrease the burden of recovery and time required to return to baseline.
O081 De-escalating axillary dissection in mastectomy cases for ductal carcinoma in-situ
Authors: Hamza E , Doherty E , Tafangombe L , Downey E , Butt A , Hill A
Published: May 2023

Introduction

Axillary surgery has been de-escalated in invasive breast carcinoma and may be omitted in certain age groups according to the Choosing Wisely initiative. Invasion can be found in 10-20% of patients with ductal carcinoma in-situ (DCIS). Therefore, Sentinel lymph node biopsy (SLNB) is indicated to rule out nodal metastasis. Our purpose was to study the risk factors and outcome of positive SLNB.

Methods

A retrospective analysis was performed on a series of 67 cases of patients who underwent mastectomy with SLNB for DCIS at Beaumont Hospital, Ireland, Royal College of Surgeons in Ireland, between 2015 and 2021. We evaluated their clinical, histopathological characteristics and regional recurrence.

Results

Only one invasive component was identified out of 67 cases (1.5%). Eight patients (11.9%) had positive SLN, six with isolated tumour cells, one micro-metastasis and one macro-metastasis. The three patients who proceeded for axillary lymph node dissection (ALND) presented with palpable lump, nipple discharge and through family history screening; however, all additional nodes retrieved were negative. All three patients had >5 cm high/intermediate grade disease. They were ER receptor positive and HER-2 negative. Regional recurrence was not reported in any.

Conclusion

This study identified a low rate of positive SLNB in DCIS and microinvasion on final histopathology. Factors which may increase the risk of positive SLNB are large tumours, palpable lump or nipple discharge. Our results indicate that ALND can be safely omitted in DCIS with positive SLNB but may be considered in high-risk patients.
O085 Estimating postoperative mortality in colorectal surgery- a systematic review of risk prediction models
Authors: Dosis A , Helliwell J , Syversen A , Tiernan J , Zhiqiang Z , Jayne D
Published: May 2023

Introduction

Risk prediction models are frequently used to support decision-making in colorectal surgery but can be inaccurate. Machine learning (ML) is becoming increasingly popular, and its application may increase predictive accuracy. We compared conventional risk prediction models for postoperative mortality (based on regression analysis) with ML models to determine the benefit of the latter approach.

Methods

The study was registered in PROSPERO(CRD42022364753). Following the PRISMA guidelines, a systematic search of three databases (MEDLINE, EMBASE, WoS) was conducted (from 1/1/2000 to 29/09/2022). Studies were included if they reported the development of a risk model to estimate short-term postoperative mortality for patients undergoing colorectal surgery. Discrimination and calibration performance metrics were compared. Studies were evaluated against CHARMS and TRIPOD criteria.

Results

3,052 articles were screened, and 45 studies were included. The total sample size was 1,356,058 patients. Six studies used ML techniques for model development. Most studies (n=42) reported the area under the receiver operating characteristic curve (AUROC) as a measure of discrimination. There was no significant difference in the mean AUROC values between regression models (0.833 s.d.±0.52) and ML (0.846 s.d.±0.55), p=0.539. Calibration statistics, which measure the agreement between predicted estimates and observed outcomes, were less consistent. Risk of bias assessment found most concerns in the data handling and analysis domains of eligible studies.

Conclusion

Our study showed comparable predictive performance between regression and ML methods in colorectal surgery. Integration of ML in colorectal risk prediction is promising but further refinement of the models is required to support routine clinical adoption.
O087 Predictors of persistent opioid use after discharge following colectomy: a population-based cohort study from England
Authors: Baamer R , Humes D J , Toh L , Knaggs R , Lobo D N
Published: May 2023

Introduction

Little is known regarding whether opioid prescriptions following colectomy lead to persistent use. We aimed to determine the prevalence of persistent post-discharge opioid use following colectomy, stratified by preadmission opioid exposure, and identify associated predictors of prolonged use.

Methods

This cohort study on adults undergoing colectomy between 2010 and 2019 used linked primary (Clinical Practice Research Datalink), and secondary (Hospital Episode Statistics) care data. Patients were categorised as opioid-naïve, currently exposed (opioid prescription 0-6 months before admission) and prior exposed (prescription 6-12 months before admission). Persistent use was defined as needing an opioid prescription within 90 days of hospital discharge, along with another opioid prescription 91 to 180 days after discharge. Multivariable logistic regression analyses were performed to identify predictors of persistent use.

Results

Of the 93,262 patients, 15,081 (16.2%) were issued at least one opioid prescription within 90 days of discharge. Of these, 45.0% were opioid-naïve, 49.9% currently exposed, and 5.0% prior exposed. From the whole cohort, 7540 (8.1%) developed persistent opioid use. Patients with preoperative opioid exposure had the highest persistent use: 5317 (40.4%) from the currently exposed group and 305 (9.8%) from the prior exposed group, with only 2.5% from the opioid-naïve group. Predictors of persistent use included prior opioid exposure, high deprivation index, multiple comorbidities, White ethnicity, and open surgery.

Conclusion

After colectomy, more than 1:12 patients continued to receive opioids three months beyond discharge. Minimally invasive surgery was associated with lower risk of persistent opioid use and may represent a modifiable risk factor.
O088 Is it possible to predict which patients need prolonged intensive care support after elective oesophageal surgery?
Authors: Radford D , Parry M , Wilson V , Vohra R , Beed M
Published: May 2023

Introduction

Oesophagectomy for oesophageal cancer is associated with post-operative complications and physiological instability, with cardio-respiratory disturbance in up to 30% of patients. Oesophagectomy patients are regularly admitted to an intensive care unit (ICU) for the first 24 hours after surgery. Increased demand for ICU beds has sparked interest in identifying patients who could be managed in lower intensity environments. We examined pre-operative features potentially associated with increased complication risk.

Methods

Data from 526 patients who underwent elective oesophagectomy 07/01/2015 - 10/12/2019 was reviewed with basic demographic data available for 485. From 211 patients, data relating to past medical history, American Society of Anesthesiology score (ASA), prescription drug history, and pre-operative blood tests was retrospectively analysed [SPSS v.28; IBM, Chicago] to identify features associated with prolonged ICU stay.

Results

Median length of post-operative ICU stay was 31 hours. 327 (67.4%) remained on ICU <48 hours, and 158 (32.6%) ≥48 hours. Age >70, ASA ≥3, and female sex were associated with stay ≥48 hours (p=0.044; p=0.036; p<0.001). Increased pre-operative white cell count and serum urea were associated with prolonged ICU stay (p=0.002; p=0.007), as was lower sodium and albumin (p=0.002; p=0.02).

Conclusion

Predicting which patients are more likely to require prolonged ICU support after oesophagectomy may allow others to be admitted to lower dependency beds. The associations identified could be used in future multivariate analysis to derive a pre-operative scoring system.
O094 Urinary-derived immune cell profiling to predict bladder cancer progression and treatment response
Authors: Natarajan M , OBrien J , Wooldridge T , Annels N , Perry M , Pandha H
Published: May 2023

Introduction

A quarter of newly diagnosed bladder cancers are muscle-invasive (MIBC) (45% 5-year disease free survival). 30% patients with apparent non-muscle-invasive cancer (NMIBC) have MIBC on histology following cystectomy (RARC). Tumour associated macrophages (TAMs) polarise into an immunogenic M1 phenotype or immunosuppressive M2 phenotype. This study assesses accuracy and validity of quantifying urinary macrophages for earlier recognition of treatment resistant bladder cancer.

Methods

Urine-derived cells and tumour and adjacent normal bladder derived cells were collected from 18 RARC patients between May-October 2022. Flow cytometry performed for immune cell profiling (MACSQuant).

Results

The urinary immune cell profile closely reflected the tumour immune profile. Females had higher CD206+CD163+ M2 phenotype cells in urine and in tumour (p<0.05). In adjacent normal bladder and in males we identified higher CD3+CD8+ T cell expression in tumour tissue (p<0.05) despite non-significant difference in distribution of male and female disease stage at final histology. NMIBC demonstrated an immunogenic urinary and tumour profile with more M1 macrophages (CD68+CD80+) (p<0.05) vs. MIBC. The 3 males upstaged from NMIBC to MIBC on final histology had lower representation of CD68+CD80+ M1 phenotype cells in urine and tumour (p<0.05).

Conclusion

The TAM immune cell profile is reflected accurately in urine sampled at RARC: a higher proportion of M2 phenotypic macrophages and lower proportion of M1 macrophages in the tumour and urine is predictive of more aggressive disease. This study highlights the potential application of urinary derived TAM analysis for disease outcome prediction and early consideration of adjuvant immune checkpoint therapy.
O095 hCNT (human concentrative nucleoside transporter) and hENT (human equilibrative nucleoside transporter) in human gastric cancer and response to chemotherapies
Authors: Li A , Lane J , Ruge F , Zhuang X , Zeng J , Jia S , Fu J , Jiang W
Published: May 2023

Introduction

hCNT (Human Concentrative Nucleoside Transporter, also known as SLC28A1) and hENT (Human Equilibrative Nucleoside Transporter, SLC29A1) belong to the large solute carrier (SLC) family, a large membrane transport molecule group for the influx and efflux across cell membrane of various solutes including some of the anticancer drugs. hCNT and hENT are suggested to be involved in the transportation of certain chemotherapeutic drugs. The present study investigated the role of both transporters in gastric cancer and the response of gastric cancer cell and patients to chemotherapeutic drugs.

Methods

The expression levels of hCNT and hENT gene transcripts and proteins were determined in two independent gastric cancer cohorts and assessed against patient's responses to neoadjuvent chemotherapies. Their value in assessing patient's survival, clinical and pathological indicators was also assessed.

Results

Gastric tumour tissues expressed significantly higher levels of hCNT and hENT than normal stomach tissues (p=0.022 and p=0.0071, respectively for hCNT and hENT). Expression levels of the hCNT and hENT gene transcripts presented significant correlation with the overall survival (OS) (Hazard Ration (HR)=2.885, p<0.001 for hCNT; HR=2.078, p<0.001 for hENT) and disease-free survival of the patients (HR=2.434, p=0.004 for hCNT; HR=2.072, p<0.001). Patients with high levels of hCNT in their gastric tumours were more resisted to neoadjuvant therapies (HR=3.437, p=0.013, by ROC model), although the same was not seen with hENT.

Conclusion

hCNT and hENT have significant prognostic factors for patients with gastric cancer and theranostic factor for response to neoadjuvant therapies.
O096 Expression of MLN70 in breast cancer and the connection with skeletal metastasis
Authors: Cong B B , Martin T A , Mansel R E , Davies E , Jiang W G
Published: May 2023

Introduction

MLN70 ([metastatic lymph node gene 70 protein], also known as S100A11 [S100 Calcium-Binding Protein A11] or Calgizzarin), a nucleic and cytosolic protein suspected to have a role in regulation of cellular invasion, migration and tubulin polymerisation in cancer cells and has been implicated in cancer progression. The present study explored how MLN70 might have a value in the clinical outcome of the patients.

Methods

Expression of MLN70 transcripts was quantified in a clinical cohort of breast cancer and was evaluated against the clinical, pathological, hormonal receptor status and clinical outcome of the patients.

Results

Breast tumour tissues had higher levels of MLN70 than normal tissues and high levels of MLN70 linked to a shorter overall survival of the patients. MLN70 had a significant correlation with three members of the ERBB family including ERBB1 (EGFR), Her2 (ERBB2) and ERBB4. There were no significant different between node positive and node negative tumours (p=0.237). The most striking finding was that MLN70 showed a significant predictive value in identifying patients who subsequently developed skeletal metastasis (RUC=0.793, p<0.0001 by ROC analysis) and high levels of MLN70 was associated with skeletal metastases (p=0.019, Hazard Ratio 10.93 by regression analysis). Furthermore, multivariate analyses using both linear and regression models indicated MLN70 as being an independent factor for bone metastasis (p=0.016) amongst clinical, pathological and hormone receptor status.

Conclusion

The present study reveals MLN70 as a significant and independent predictive factor for skeletal metastasis of patients with breast cancer and a prospective target in this cancer type.
O103 Digital light processing 3D printed collagen/PEGDA hydrogel for regenerative medicine
Authors: Chen J , Wang C , Wu L , Chang J , Song W
Published: May 2023

Introduction

Digital light processing represents a rapid approach to constructing 3D structures with superior resolution. However, it imposes demanding requirements on the properties of bioink. Methacrylated gelatin has long been the major option but results in limited mechanical properties. The development of collagen-based bioinks provides a wider stiffness tuning range, native bioactivities, and versatility in regenerative medicine applications.

Methods

Purified collagen solution was obtained via enzymolysis and ultrafiltration, then went through methacrylation. The photo-crosslinkable bioink comprises methacrylated collagen, PEGDA, acetic acid, yellow food dye, and photoinitiator LAP. The 3D structures were fabricated utilising a commercial digital light processing printer with 405 nm visible light.

Results

The collagen/PEGDA bioink showed translucent and low viscosity suitable for digital light processing printing. The printed scaffolds reached a compressive modulus of ∼100 kPa with 0.6 wt% collagen. Sharp-edged and fine structures (∼250 μm) were obtained via printing. The hydrogels show tuneable mechanical properties and flexibility in post processing. A series of structures were fabricated to test the printability, including ear, nose, osteons, microfluidic pads, and porous scaffolds. Aligned micro structures (∼50 μm) of dehydrated scaffold were also achieved via directional freezing. Moreover, the scaffolds could be further stiffened by immersing into the mineralisation solution, to mimic nanocomposite ECM of native bone. The hydrogels exhibited low cytotoxicity and supported the attachment and proliferation of 3T3 fibroblasts.

Conclusion

The collagen/PEGDA bioink was fabricated for the digital light processing technique. It is capable of being printed into high-resolution structures with tuneable properties for various tissue regeneration applications.
O118 Timing of surgery in open hand fractures - a single centre, closed-loop audit
Authors: Iakovou D , Sequeira Campos M , Woollard A
Published: May 2023

Introduction

The British Society for Surgery of the Hand (BSSH) standards dictate the management of open hand fractures (OHFs). A wound washout and closure (WWC) in an OHF should take place within 24 hours of injury if definitive treatment is not possible in that timeframe.

Methods

A retrospective cross-sectional design was used to collect data from patients with OHFs. Data was taken from Cerner® EPR, Powerchart. Information was gathered about the date and type of surgery, whether surgery took place within 24 hours and, or whether WWC took place within the 24 hour timeframe. Two 3-month audit cycles were carried out: 03/12/2021–24/03/2022 (Cycle 1) and 24/03/2022–24/05/2022 (Cycle 2). Between cycles, simple interventions were implemented, including the distribution of flyers amongst departmental staff and weekly announcements in departmental meetings.

Results

Cycle 1 analysed 5 patients with OHFs. Of these patients, 60% (n=3) had definitive surgery within 24 hours and 40% (n=2) had neither definitive surgery nor WWC. Cycle 2 included 13 patients with OHF. Of these, 53.8% (n=7) had definitive surgery within 24 hours, 46.2% (n=6) did not have definitive surgery but had WWC and 16.7% (n=1) did not have surgery or WWC within 24 hours.

Conclusion

There was a 30% improvement in the cases for which BSSH guidelines were followed. Simple interventions can lead to significant change in compliance with gold-standards. We aim to conduct further cycles and include other units to assess multi-centre compliance.
O119 Validity of current screening practices for cardiac injury in patients presenting with traumatic sternal fractures
Authors: Burrows R , Boardman S , Spiers D , Friej R , Brooks A , O'Connor R
Published: May 2023

Introduction

Sternal fractures are a common injury found in trauma patients that are transferred to Level I trauma centres. Current practice for patients presenting with a sternal fracture is to perform an electrocardiogram (ECG) and serum troponin. All patients are subsequently admitted for 24 hours of observation with cardiac monitoring, irrespective of the initial investigation findings. We therefore considered the utility of this strategy.

Methods

Some 209 patients with sternal fractures who presented over a 2 year period were identified from the Trauma Audit and Research Network (TARN) database for retrospective analysis. We considered the predictive value of both ECG and serum troponin in predicting underlying cardiac injury.

Results

Troponin rise occurred in 44 patients (20% of the cohort). ECG changes were noted in 12 patients (5.5% of cohort). Echocardiograms were performed in 55 patients, of these 6 (10.9%) showed changes potentially relating to trauma. The positive predictive value of these initial investigations to rule out clinically relevant cardiac injury was 0.12 and the negative predictive value was 1.00.

Conclusion

Within this cohort, a negative troponin and a normal ECG proved in 100% of patients to rule out a clinically relevant cardiac injury. This finding gives weight to these being a valid screening tool not simply to guide further investigation, but to also guide management. Their early use in patients with a sternal fracture could be used to avoid unnecessary admissions for observation and cardiac monitoring. Further exploration of the validity of these findings should consider increasing the number of cases and multicentre studies.
O121 Signal-induced proliferation-associated protein 1 (SIPA1) expression in gastric cancer, clinical and prognostic value
Authors: Yu R Y , Martin T A , Li A X , Ji E K , Jia S , Ji J , Jiang W G
Published: May 2023

Introduction

SIPA1 (Signal-Induced Proliferation-Associated Protein 1) is a mitogen induced GTPase activating protein and known to regulate cycle progression and barrier function of cancer cells. It is reported to influence the disease progression in lung and colorectal cancers. Here, we report the clinical and prognostic value of SIPA1 in gastric cancer.

Methods

Two independent gastric cancer cohorts were tested for SIPA1 expression. The expression profile of SIPA1 was analysed against the clinical, pathological, outcome and the expression of the ERBB (Her) family members in the same cohorts.

Results

Gastric tumour tissues had a higher level of SIPA1 transcript than normal stomach tissues. High levels of SIPA1 were seen in high grade, node positive and high TNM tumours. SIPA1 had a significant correlation with the ERBB family members in both normal tissues and in tumour tissues. SIPA1 levels only had a weak relationship with the overall (OS) and disease free (DFS) survival. However, stratification of patients by expression pattern of ERBB3 (Her3), the ERBB family significantly correlated with SIPA1 (p<0.0001), identified a subgroup of patients who had low ERBB3. In this subgroup, levels of SIPA1 had a marked prognostic value in predicting both OS (p=0.004 by Mantel-Cox log rang survival analysis) and DFS (p=0.008). Finally, it was demonstrated that SIPA1 was associated with patient's response to neoadjuvant therapies in a ERBB dependent manner.

Conclusion

SIPA1 expression is frequently seen in gastric cancer and together with members of the ERBB family influences the clinical outcome and responses to chemotherapies of the patients.
O137 Strictureplasty for small bowel Crohn's disease in the biologic era: long-term outcomes and risk factors for recurrence
Authors: Nasasra A , Morrison T , Carvello M , Williams K , Davies J , Spinelli A , Mehta A , Warusavitarne J
Published: May 2023

Introduction

Strictureplasty is a mainstay bowel-preserving technique for small bowel Crohn's disease (CD). We sought to audit international practice across three high volume centres.

Methods

A retrospective audit was performed for all strictureplasties undertaken for small bowel CD, over a 15-year period (2006-2021), in three high volume centres in the United Kingdom and Italy.

Results

123 patients were included. 58% were male, 25% smoked, 60% had previous abdominal surgery for CD. Median age was 40 years (IQR 30-52 years), weight 64kg (56-72kg) and disease duration 138 months (81-255 months). 42% had biologics pre-operatively. 338 strictureplasties were performed in 123 patients, median 2 per patient (IQR 1-3). Complications occurred in 35%, with 8% being Clavien Dindo grade 3; there were no grade 4/5 complications. 84/123 patients (68.3%) received postoperative biological treatment. Median follow-up was 54 months. 41/123 patients (33.3%) developed clinical recurrence. Radiological recurrence of stricturing disease was confirmed in 39/123 (31%). 26/123 patients (21%) underwent re-operation for radiologically confirmed stricturing recurrence.

Radiological recurrence rates were 53% in patients who continued to smoke after index surgery versus 30% in patients who did not (P=0.04). Radiological recurrence rates did not differ significantly in patients receiving postoperative biologics versus those who did not (33.3% vs 36.7%; P>0.05).

Conclusion

Strictureplasty remains safe and effective surgical treatment for small bowel CD. Recurrence rates remain high with patients likely to undergo multiple procedures in their lifetime, regardless of postoperative biologic therapy. Smoking cessation strongly limits the risk of recurrence.
O146 Natural history and clinical outcomes in patients with groove pancreatitis: an observational study
Authors: Oyende O , Sanyal S , Jackman J , Mitchell W K , Adiamah A , Clarke C , Bannur U , Zaitoun A M , Lobo D N
Published: May 2023

Introduction

Groove pancreatitis (GP) is a rare and focal form of pancreatitis affecting the para-duodenal groove area. Diagnosis is usually made by radiological imaging or histological analysis. This study aimed to determine the disease pattern, treatment modalities and outcomes.

Methods

Data were retrospectively collected for patients diagnosed with GP radiologically and/or histologically at our tertiary hospital from 2010 to 2019. A search of our imaging database was conducted using the term groove pancreatitis totalling 1,040 patients. Duplicates (95) and reports mentioning only groove or only pancreatitis (945) were eliminated. All included patients were then re-assessed by two expert hepatopancreaticobiliary radiologists and a specialist histopathologist to confirm inclusion.

Results

Our cohort comprised of 54 patients, 39 males and 15 females. The mean age was 67 years (range 39-101 years). Of the 54 patients, 11 had pancreatic cancer (20%). Pain as a main presenting complaint occurred in 78% and jaundice in only 13%. 26% had elevated lipase and 37% had deranged LFTs. 69% were managed conservatively as first line. 11% of patients failed conservative management and proceeded to endoscopic treatment. Surgical intervention occurred in 24%. 11% of all patients had complete symptom relief, and 76% showed symptom improvement. Mortality at 2years of follow-up, was 45% and 28% in those with and without cancer.

Conclusion

GP is a benign disease with a non-specific natural history. It remains unclear if there is a transition between GP and GP-associated mass. This emphasises a high index of suspicion in diagnosis, using radiological, endoscopic, and cytological analysis.