bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer Risk in Patients With Autoimmune Hepatitis: A Nationwide Population-Based Cohort Study With Histopathology
Authors: Sharma Rajani , Verna Elizabeth C , Simon Tracey G , Söderling Jonas , Hagström Hannes , Green Peter H R , Ludvigsson Jonas F
Published: April 2021

We aimed to determine the risk of incident cancer in autoimmune hepatitis (AIH) compared with the general population and siblings. AIH was defined by the presence of a medical diagnosis of AIH and results of examination of a liver biopsy specimen in a nationwide Swedish population-based cohort study. We identified 5,268 adults with AIH diagnosed during 1969–2016 and 22,996 matched, general population, reference individuals and 4,170 sibling comparators. Using Cox regression, hazard ratios were determined for any incident cancer, and subtypes were determined from the Swedish Cancer Register. During follow-up, a cancer diagnosis was made in 1,119 individuals with AIH (17.2 per 1,000 person-years) and 4,450 reference individuals (12.0 per 1,000 person-years). This corresponded to a hazard ratio of 1.53 (95% confidence interval: 1.42, 1.66). Cancer risk was highest in those with cirrhosis. There was a 29.18-fold increased risk of hepatocellular carcinoma (HCC) (95% confidence interval: 17.52, 48.61). The annual incidence risk of HCC in individuals with AIH who had cirrhosis was 1.1% per year. AIH was also linked to nonmelanoma skin cancer (hazard ratio (HR) = 2.69) and lymphoma (HR = 1.89). Sibling analyses yielded similar risk estimates for any cancer (HR = 1.84) and HCC (HR = 23.10). AIH is associated with an increased risk of any cancer, in particular, HCC and extrahepatic malignancies. The highest risk for cancer, especially HCC, is in patients with cirrhosis.
The Longitudinal Association Between Retirement and Depression: A Systematic Review and Meta-Analysis
Authors: Li Wentao , Ye Xin , Zhu Dawei , He Ping
Published: April 2021

The purpose of this study was to collect evidence of the relationship between retirement and depression through meta-analysis and further analyze the heterogeneity of results. The quality of the studies was rated based on 10 predefined criteria. We searched for articles published between 1980 and 2020, and a total of 25 longitudinal studies were included in the meta-analysis. The meta-analysis results showed that retirement was associated with more depressive symptoms (d = 0.044, 95% confidence interval (CI): 0.008, 0.080). The association of more depressive symptoms with involuntary retirement (d = 0.180, 95% CI: 0.061, 0.299) was stronger than with voluntary retirement (d = 0.086, 95% CI: −0.018, 0.190) and regulatory retirement (d = 0.009, 95% CI: −0.079, 0.097). Retirement was significantly associated with more depressive symptoms in Eastern developed countries (d = 0.126, 95% CI: 0.041, 0.210), and the association was stronger than that in Western developed countries (d = 0.016, 95% CI: −0.023, 0.055). We found that the transition to retirement was associated with higher risk of depression, and this association varied by the type of retirement and country. Further empirical studies are needed to explore the mechanism of retirement and depression and whether such an association is linked with socioeconomic position.
Application of omics research in seaweeds with a focus on red seaweeds
Authors: Patwary Zubaida P , Paul Nicholas A , Nishitsuji Koki , Campbell Alexandra H , Shoguchi Eiichi , Zhao Min , Cummins Scott F
Published: April 2021

Targeted ‘omics’ research for seaweeds, utilizing various computational and informatics frameworks, has the potential to rapidly develop our understanding of biological processes at the molecular level and contribute to solutions for the most pressing environmental and social issues of our time. Here, a systematic review into the current status of seaweed omics research was undertaken to evaluate the biological diversity of seaweed species investigated (red, green and brown phyla), the levels to which the work was undertaken (from full genome to transcripts, proteins or metabolites) and the field of research to which it has contributed. We report that from 1994 to 2021 the majority of seaweed omics research has been performed on the red seaweeds (45% of total studies), with more than half of these studies based upon two genera Pyropia and Gracilaria. A smaller number of studies examined brown seaweed (key genera Saccharina and Sargassum) and green seaweed (primarily Ulva). Overall, seaweed omics research is most highly associated with the field of evolution (46% of total studies), followed by the fields of ecology, natural products and their biosynthesis, omics methodology and seaweed–microbe interactions. Synthesis and specific outcomes derived from omics studies in the red seaweeds are provided. Together, these studies have provided a broad-scale interrogation of seaweeds, facilitating our ability to answer fundamental queries and develop applied outcomes. Crucial to the next steps will be establishing analytical tools and databases that can be more broadly utilized by practitioners and researchers across the globe because of their shared interest in the key seaweed genera.
Null models for null hypotheses in taxonomy: a test using Scyphozoa
Authors: Brown Michael K , Gibbons Mark J
Published: April 2021

Although molecular tools are becoming more important in the delineation of scyphozoan species there is, perforce, a need to substantiate new species definitions using morphological data. Access to type material is often difficult and detailed, raw morphometric data are rarely provided in older type descriptions, which makes comparisons of new with old challenging. Here, we use null models based on simple measures of central tendency to generate morphometric data sets for four species of Aurelia, three species of Chrysaora and two species of Crambionella. The results of PERMANOVA and CAP analyses indicate no significant differences between random and real data within species, but significant differences between congeneric species (null or real), suggesting that this multivariate approach may be a useful tool for defining species when comparative data are scant.
O13: TUMOUR STROMAL CELLS - A CULPRIT IN BREAST CANCER RECURRENCE AFTER NEOADJUVANT CHEMOTHERAPY
Authors: O'Connor DJ , Kerin MJ , Barkley LR
Published: April 2021

Introduction

The goal of neoadjuvant chemothepaeutics(NACs) and surgical excision of breast cancer is to control and ultimately eliminate the malignant tumour. Despite advances in treatment, a subset of patients will develop disease recurrence. Tumour stromal cells(TSCs) are non-cancerous cells that support malignancy within the tumour microenvironment(TME). In particular, TSCs can suppress the host immune response to tumour. It is unclear if NACs affect the survival of–or alter the immunosuppressive functions of TSCs in breast cancer patients and if this correlates with recurrance or chemoresistance?

Method

TSCs and Tumour Associated Normal Stromal Cells(TANs) were isolated from tissue harvested from breast cancer patients at surgery. Clonogenic survival assays were performed following exposure to increasing doses of Paclitaxel (range 0-1000nM), Cyclophosphamide (range 0-3μM) and Doxorubicin (0-100nM). TSCs were co-cultured with CD4+ and CD8+ T-cells to determine the effect of chemotherapeutics on their ability to suppress T-cell proliferation.

Result

TSCs(n=5) are less susceptible to the cytotoxic effects of chemotherapy compared to TANs with 21%(p-0.0001), 21%(p-0.001) and 15%(p-0.026) more colonies across all doses of Paclitaxel, Cyclophosphamide and Doxorubicin respectively. Chemo naïve TSCs suppressed CD4+ and CD8+ T-Cell proliferation by 44% and 20.5% respectively(p-0.001, p-0.042). Interestingly, Paclitaxel-treated TSCs suppressed CD4+ proliferation by a further 11.1%(p-0.047) and CD8+ proliferation by 35.6%(p-0.017). Additionally, Cyclophosphamide-treated TSCs enhanced CD8+ suppression by 25.6%(p-0.029).

Conclusion

Our data indicate that NACs enhance the immunosuppressive function of TSCs - potentially creating an immune inert TME in vivo. Future studies will explore the correlation between NAC treatment, immunosuppressive activities within patient tumours/blood and recurrence.

Take-home message

After neoadjuvant chemotherapy, Tumour stromal cells are highly immunosuppressive and may contribute to breast cancer recurrence.
O17: HYALURONIC ACID DEPENDENT ADHESION IN COLORECTAL CANCER PERITONEAL METASTASIS
Authors: Soliman F , Ye L , Jiang W , Hargest R
Published: April 2021

Introduction

Peritoneal Metastasis (PM) in Colorectal Cancer (CRC) undoubtedly remains a challenge to treat and often portends a poor prognosis for patients. Hyaluronic acid (HA) is found throughout the body, including coating of the peritoneum. Interaction of HA with HA-dependent adhesion molecules can facilitate cell adhesion within the peritoneum. HA may play a role in spread of PM in CRC in association with known HA-receptor molecules CD44, RHAMM and ICAM-1.

Method

Expression of HA-dependent and HA-independent adhesion molecules were examined in CRC using tissue microarray datasets and matched to clinicopathological data. In-vitro peritoneal modelling assessed cellular adhesion when treated with a competitive HA-inhibitor (HAi) or excess exogenous HA. An in-vivo Xenograft peritoneal model, using CD1 nude mice injected with CRC cells, were treated with either HAi or excess exogenous HA and compared to a control (PPL: PE9445FC2).

Result

There is a significant increase in expression of HA-dependent adhesion molecules seen in CD44, RHAMM and ICAM-1 in CRC (p=<0.0001). Whilst Non-HA-dependent adhesion molecules demonstrated either significant downregulation or no expression difference. Cellular adhesion was decreased in three CRC cell lines when treated with HAi or excess HA. Treatment with HAi and HA in-vivo confirmed a significant reduction in PM, compared to controls (HAi p=0.0094, HA p=0.0009).

Conclusion

HA-dependent adhesion molecules and HA appear to play a role in CRC. Targeting HA-dependent interaction in CRC influences cellular adhesion and may have a potential therapeutic use in treatment of PM in CRC. Further in-vitro and in vivo modelling is needed.

Take-home message

HA receptor adhesion molecules CD44, RHAMM and ICAM-1 have all been independently implicated in adverse outcomes in colorectal cancer. Targeting HA receptor interaction appears to reduce peritoneal dissemination in colorectal cancer.
O18: AN EXPLORATION OF THE GENOME OF MUCINOUS ADENOCARCINOMA OF THE RECTUM
Authors: Reynolds IS , O'Connell E , Fichtner M , McNamara DA , Kay EW , Prehn JHM , Furney SJ , Burke JP
Published: April 2021

Introduction

Mucinous adenocarcinoma (MA) of the rectum accounts for 5-15% of rectal cancers. This histological subtype has been shown to have a worse response to chemoradiotherapy and worse long term outcomes when compared to non-mucinous adenocarcinoma (NMA). The aim of this study was to compare the genomic landscape of rectal MA to rectal NMA.

Method

Using the BGISEQ PE100 platform, paired end whole genome sequencing was carried out on tumour and matched normal tissue from cases of MA. The Cancer Genome Atlas was interrogated to identify further cases of rectal MA and cases of rectal NMA with sequencing data that could be used as a control group. In-depth bioinformatic analysis was undertaken and the genomic landscapes of the two subtypes were compared.

Result

A total of 14 cases of MA were compared to 74 cases of NMA. The microsatellite instability-high rate in the MA group was 14.29% vs 4.05% in the NMA group. POLE mutations were found in 5.41% of the NMA group compared to 0.00% of the MA group. KRAS, BRAF and PIK3CA mutations were more frequent in the MA group whereas TP53 and APC mutations were more common in the NMA group. Significant differences between the groups were identified in the most frequently mutated genes. Copy number alteration, mutational signatures, structural variation and microbiome findings will also be described.

Conclusion

MA of the rectum is not just phenotypically distinct, it is a distinct genotype. This could have implications when considering neoadjuvant and adjuvant treatment strategies in the future.

Take-home message

Mucinous adenocarcinoma differs from a genomic perspective from non-mucinous adenocarcinoma and this may have implications for treatment strategies in the future
O22: CONJUGATED IRON NANOPARTICLES AS THERAPEUTIC CARRIERS FOR SPECIFIC TARGETING OF CANCER CELLS
Authors: Alfadli FF , Sarwary R , Correia J , Ramesh B , Welch H
Published: April 2021

Introduction

Precision medicine with minimal side effects remains the goal of cancer therapy. Iron oxide nanoparticles are non-toxic, successful carriers of substances, targeting tissues and delivering high payloads of conjugated agents. Interfering RNA (siRNA) disrupts protein expression, an effective treatment e.g. for hereditary amyloidosis. This study tested transferrin-conjugated dopamine-coated iron oxide nanoparticle (TF-dpFe3O4) delivery of siRNA to cells overexpressing transferrin receptor (TFR).

Method

Cells were cultured in FBS-DMEM/F12. Fe3O4 nanoparticles were prepared by co-precipitation, dopamine coated +/- transferrin conjugation. LDH/MTT assays assessed cell viability responses to [TF-dpFe3O4] or [dpFe3O4]. Protein expression was examined by PAGE, densitometry and immunofluorescence. Targeting efficacy was determined by MEK2 gene silencing using siRNA-conjugated TF-dpFe3O4 or dpFe3O4.

Result

T-47D cells expressed high levels of TFR and MEK2. No significant effect on cell viability was observed with ≤2.5mg/mL TF-dpFe3O4 or dpFe3O4. By conventional transfection, 10nM siRNA lowered MEK2 expression levels to 25% (48hr); levels rebounded to 50% by 72hr. 10nM siRNA-conjugated TF-dpFe3O4 (2.5mg/mL) reduced MEK2 expression by 50% (72hr) without rebound; expression of a-tubulin (control) was unaffected. In contrast, as MEK2 levels decreased, TFR levels increased 2.2-fold (72hrs).

Conclusion

TF-dpFe3O4 nanoparticles are safe/efficient vehicles for delivering siRNA to cancer cells over-expressing TFR. Over 72hrs, protein expression of MEK2 reduced by 50%, a target superior to conventional methods. Notably: as the MAPK pathway was inhibited, increases in TFR levels were observed, suggesting adaptations to damage or stress.

Take-home message

TF-dpFe3O4 nanoparticles are a safe and efficient vehicle for delivering siRNA to cancer cells over-expressing TFR, allowing for successful targeting and inhibition of MAPK pathway proteins, such as MEK2, that drive tumour growth.
O24: THE PANCREATIC EPSILON-CELLS RECOVER THE EMBRYONIC GHRELIN SECRETION IN RESPONSE TO BARIATRIC SURGERY
Authors: Camacho-Ramirez A , Almorza-Gomar D , Falckenheiner J , Pérez-Arana G , Prada-Oliveira JA
Published: April 2021

Introduction

Many surgical techniques are employed in the treatment of obesity. A main consequence of these techniques is the severe improvement of Type 2 Diabetes mellitus. Many hypotheses had been exposed to know the intrinsic mechanism developed in this relationship. The enterohormones seems to be a definitive effector. The ghrelin is an enterohormone released for the gastric fundus and it has been related to the mentioned improvement. We hypothesized about the role of pancreatic epsilon cells, which have the capacity to release ghrelin during the embryonic stages. We studied the changes in the ghrelin immunostaining in endocrine pancreas of rats which underwent bariatric surgery. MATERIAL AND

Method

We employed 16 non obese euglycemic male Wistar rats, randomised in the surgical groups. These groups were the surgical techniques (Sleeve gastric –SG- and Roux en Y Gastric Bypass –RYGB-), and two controls (fasting and surgical). After three months, rats were sacrificed; the pancreas were obtained and processed for the immuno-cytochemical technique.

Result

We reported a significant increase of epsilon cells (ghrelin positive/mm2 pancreatic area) in the pancreas of SG versus the control groups (vs FC, P<0.01 and vs sham, P<0.05). CONCLUSION. SG and RYGB are surgical techniques broadly employed in humans and both reduce severely the fundus. Paradoxically, the serum level of ghrelin in patients are preserved. We reported that the total suppression of the fundus gastric produced the recovery of an embryonic pancreatic function. This mechanism could be related with the complex physiologic mechanism that improve T2DM after bariatric surgery.

Take-home message

After bariatric surgery, the pancreas release of ghrelin increased as the response to gastric reduction.
O32: TRANSPARENCY IN SURGICAL RANDOMISED CONTROLLED TRIALS: CROSS-SECTIONAL, OBSERVATIONAL STUDY
Authors: Helliwell JA , Shelton B , Mahmood H , Blanco-Colino R , Fitzgerald JE , Harrison EM , Bhangu A , Chapman SJ
Published: April 2021

Introduction

Randomised controlled trials (RCT) often provide the scientific basis on which commissioning and treatment decisions are made. It is essential that their results and methods are reported transparently. The aim of this study was to explore transparency with respect to trial registration, disclosure of funding sources, conflicts of interest (COI), and data sharing.

Method

This was a cross-sectional review of surgical RCTs. Data were extracted from RCTs in ten high-impact journals published in the years 2009, 2012, 2015, and 2018. Outcomes of interest were the incidence of reported trial registration, disclosure of funding sources, disclosure of investigator COI, and presence of a statement of data sharing plans.

Result

A total of 475 were eligible for analysis. Trial registration was present in 73 (67%) studies in 2009, 137 (84%) in 2012, 111 (89%) in 2015 and 110 (93%) in 2018. Funding statements were provided in 55%, 65%, 69.4%, and 75.4% of manuscripts, respectively. Conflicts of interest statements were provided in 49.5%, 89.1%, 94.6%, and 98.3% of manuscripts, respectively. Data sharing statements were present in only 15 (3.2%) RCTs. Eleven of these were in studies published most recently in 2018.

Conclusion

Trial registration, presence of funding statements, and disclosure of personal conflicts of interest in surgical RCTs have improved rapidly over the last 10 years. In contrast, disclosure of data sharing plans is exceptionally low. This may contribute to research waste and represents an essential target for improvement.

Take-home message

Trial registration, presence of funding statements, and disclosure of personal conflicts of interest in surgical RCTs have improved rapidly over the last 10 years. In contrast, disclosure of data sharing plans is exceptionally low. This may contribute to research waste and represents an essential target for improvement.
O40: PRE-OPERATIVE MANAGEMENT AND SENSITISATION IN VASCULARIZED COMPOSITE ALLOTRANSPLANTATION: A SYSTEMATIC REVIEW
Authors: Geoghegan L , Al-Khalil M , Scarborough A , Murray A , Issa F
Published: April 2021

Introduction

Vascularised composite allotransplantation (VCA) permits like-for-like reconstruction following extensive soft tissue injuries. The initial management of extensive soft tissue injury can lead to the development of anti-HLA antibodies through injury, transfusion and cadaveric grafting. The role of antibody-mediated rejection, donor-specific antibodies and graft rejection in the context of VCA remains unclear. This systematic review aimed to determine whether pre-operative management strategies influence immunological outcome following VCA.

Method

A systematic review of MEDLINE, EMBASE and CINAHL using a PRISMA-compliant methodology up to February 2019 was conducted. Pre-operative, procedural and long-term outcome data were collected and recorded for all VCA recipients on an individual patient basis.

Result

The search revealed 3,847 records of which 114 met inclusion criteria and reported clinical data related to 100 patients who underwent 129 VCA transplants. Trauma (50%) and burns (15%) were the most frequent indications for VCA. Of all 114 studies, only one reported acute resuscitative management. Fifteen patients (14.7%) were sensitized prior to reconstructive transplantation with an 80% incidence of acute rejection in the first post-operative year. Seven patients demonstrated graft vasculopathy, only one of whom had demonstrated panel reactive antibodies.

Conclusion

Currently employed acute management strategies predispose to the development of anti-HLA antibodies, adding to the already complex immunological challenge of VCA. Early appropriate care is warranted in patients with extensive soft tissue loss where the resuscitative needs should be balanced against strategies to mitigate the immunological burden, particularly as reconstructive transplantation becomes a feasible option for future soft tissue coverage.

Take-home message

Acute resuscitative management may sensitise potential transplant recipients following major soft tissue injury. Early appropriate care is warranted.
O43: CLINICAL IMPACT OF GENE FUSIONS IN BREAST CANCER BRAIN METASTASES
Authors: Cosgrove N , Vareslija D , Furney SJ , Oesterreich S , Lee AV , Couch FJ , Young LS
Published: April 2021

Introduction

The incidence of brain metastases is increasing despite longer survival rates for patients with advanced breast cancer. The identification of novel therapeutic targets for these patients is an urgent unmet clinical need. Sequencing of metastatic tumours have largely focused on mutations however gene fusions have an important, yet underappreciated role in tumorigenesis and disease progression. In this study, we investigate the role of gene fusions in brain metastatic disease and their impact on altered therapeutic responses.

Method

RNA sequencing was performed on the largest reported cohort of patient matched primary and resected brain metastatic tumours (45 patients n=90 samples). Expressed gene fusions were detected computationally using STAR-Fusion and Arriba.

Result

We identified differential gene fusion burden in brain metastatic tumours (medium of 58) vs. primary breast tumours (medium of 38) (p < 0.05). Enrichment for fusions in pathways associated with tumour cell plasticity and proliferation with recurrent fusions in known cancer driver genes related to MAPK, HER signaling identified. Of note, a fusion in CDK12 is of clinical importance. Increased genomic alterations and over expression of CDK12 is associated with brain metastases free survival in an independent cohort of primary breast tumours with a recorded history of brain metastases. It has been proposed that inhibition of CDK12 may induce BRCAness in tumours making them sensitive to PARP inhibition.

Conclusion

These results highlight the significant role of gene fusions in breast cancer brain metastases.

Abbreviations

MAPK Mitogen Activated Protein Kinase, HER Human Epidermal Receptor, CDK12 Cyclin Dependent Kinase 12

Take-home message

We highlight the significant role of gene fusions in breast cancer brain metastases and offer specific actionable genomic alterations to be exploited.
O44: WOUND HEALING INFLAMMATORY MARKERS PREDICT PROGNOSIS AND SURVIVAL IN EARLY BREAST CANCER
Authors: Singh U , Castle J , Greenhalgh S , Hussain U , Descamps T , Nash S , Wilson M , Hunt R , Kirwan CC
Published: April 2021

Introduction

Cancer is likened to a non-healing wound. There is limited evidence on the expression of wound healing tissue inflammatory markers, CD68(pan-macrophage marker), HO-1(tumour cell marker) and FAP(cancer-associated fibroblast marker) in human breast cancer.

Method

In 201 invasive breast cancer and 58 DCIS patients, CD68+TAM expression, tumour HO-1 and fibroblast FAP expression, quantified by immunohistochemistry(dichotomised: high/present vs low/absent), was correlated with tumour factors (grade, proliferation(Ki67), ER, HER2); demographic factors, behavioural factors (smoking, alcohol) and survival status(DFS, OS)

Result

High CD68+macrophage expression was increased in invasive breast cancer, compared to DCIS, and normal tissue distant from the tumour(59%,41%and 6% respectively; p<0.001).In invasive cancer,CD68+TAM expression increased with increasing tumour grade(Grade 1:42%, Grade 2:58%, Grade 3:72%; p=0.006), high Ki67(71%vs.47%; p=0.004), ER negativity(79.4%vs.55.4%; p=0.01) and HER2(HER2 positive 81.8% vs. HER2 negative 56.3%; p=0.03). CD68+TAM expression was higher in high compared to low/intermediate grade DCIS(44% % vs. 31% p=0.52). CD68+TAM expression was increased in patients who self-reported alcohol intake(non-drinker 43% vs. drinker 62%; p=0.01). HO-1 was associated with shorter DFS(HR:3.22,p=0.027) and OS(HR:2.86,p=0.029).FAP fibroblast expression correlated with longer DFS (HR:0.296,p=0.029) and OS (HR:0.271,p=0.008).

Conclusion

Tumour inflammation as assessed by CD68+TAM expression shows utility in identifying aggressive breast cancer sub-types. The association reported between CD68+TAM density and alcohol intake suggests a possible mechanism for alcohol as a risk factor for breast cancer. The prognostic value of HO-1 and FAP expression demonstrated here suggests a functional role of these wound healing markers in breast cancer. HO-1:Heme-oxygenase-1; FAP:Fibroblast activation protein; TAM:Tumour associated macrophage; DCIS: Ductal carcinoma in situ

Take-home message

Wound healing pathways of inflammation may be implicated in early breast cancer development
O46: PERIOPERATIVE LIQUID BIOPSY MAY HELP PREDICT THE RISK OF RECURRENCE IN BREAST CANCER PATIENTS
Authors: Hassan F , O'Leary DP , Ita M , Corrigan M , Wang JH , Redmond HP
Published: April 2021

Introduction

Liquid biopsy analysis using cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) has emerged as a promising non-invasive technique to detect fragmented circulating tumour DNA. It has shown excellent diagnostic and prognostic potential in breast cancer. Here, we aimed to evaluate the peri-operative dynamics of cfDNA and ctDNA to determine their prognostic ability in breast cancer.

Method

Breast cancer patients undergoing curative surgery were included. Blood samples were taken pre-operatively and 30 days post-operatively. cfDNA was extracted and measured using spectrophotometry. DNA integrity (long/short DNA fragments) was measured using ALU247 and ALU115 primers. PIK3CA mutation at exon 9 and 20 in ctDNA was detected using high resolution melting (HRM) real-time PCR combined with parallel internal controls. Ethical approval was granted.

Result

A total of 29 patients were studied, 14 disease-free group (DF) and 15 disease recurrence group (DR). The median follow-up was 36 months. cfDNA concentrations and DNA integrity were significantly higher in DR group compared to the DF group pre-operatively (cfDNA concentrations, p=0.0004; DNA integrity, p=0.039) and at 30 day post-operative time period (cfDNA concentrations, p=0.04; DNA integrity, p=0.03). Higher post–operative cfDNA concentrations were predictive of poor disease-free survival (HR: 3.8, p=0.02). Post-operative PIK3CA mutation detection in ctDNA was associated with a higher risk of recurrence (Odds ratio: 1.86, 95% CI: 0.36-12.9).

Conclusion

cfDNA and ctDNA assessment can provide valuable prognostic information at the time of surgery and have the potential to stratify the risk of recurrence and allow more personalised follow-up plan in breast cancer patients.

Take-home message

Liquid biopsy is a non- invasive and easily reproducible blood test that can provide important prognostic information at 30 days following surgery and may help clinicians to predict which breast cancer patients are at higher risk of recurrence following surgery.
O49: EFFECT OF AFIMOXIFENE (Z-4-HYDROXYTAMOXIFEN) ON ADIPOSE-DERIVED STEM CELLS
Authors: Challapalli RS , Dwyer RM , McInerney N , Kerin MJ , Lowery AJ
Published: April 2021

Background

Adipose-derived stem cells (ADSCs) are a promising cell source for adipose tissue engineering. Currently, novel breast reconstruction techniques using ADSCs are actively being explored. Systemic chemo- & hormonal therapy may impede tissue regeneration in breast cancer patients. However, the effect of hormonal therapy on ADSCs and their regenerative capabilities is poorly understood.

Aims

The current study aims to analyse the effect of Afimoxifene, an active metabolite of Tamoxifen, on proliferation and viability of ADSCs in vitro

Method

Lipoaspirates or adipose tissue were obtained with informed consent from breast cancer patients and healthy controls. The isolated ADSCs were subjected to single or multiple dose(s) of Z-4-Hydroxytamoxifen (12.5nM, 25nM, 50nM, 100nM and 1μM) and, analyzed on days 1, 3 and 5, using CellTitre 96 ® AQueous Cell proliferation assay. T47D and MDA-MB-231 cell lines were used as positive and negative controls, respectively.

Result

ADSCs were obtained from a total of 3 patients. ADSCs were isolated from a cancer patient with/without active disease at the time of sample procurement and healthy subjects opting for elective cosmetic procedures. Morphology, CFU assay and adipogenic differentiation assay were used to validate stem cell population. Afimoxifene demonstrated no statistically significant reduction in the viability or proliferation of the ADSCs, irrespective of the dose- or time-dependent exposure or cancer status (p >0.05).

Conclusion

Afimoxifene has no deleterious effect on viability or proliferation of human ADSCs up to 1μM concentration.

Key words

Adipose-derived stem cells, Afimoxifene, Breast reconstruction, Hormone therapy, Tamoxifen.

Take-home message

Afimoxifene has no deleterious effect on viability or proliferation of human ADSCs up to 1μM concentration
O52: THE IMPACT OF STUDENT BACKGROUND ON PERFORMANCE AND STRESS DURING SURGICAL SIMULATION
Authors: Soualhi A , Amin MSA , Aydin A , Khan MS , Dasgupta P , Makanjuola J , Ahmed K
Published: April 2021

Introduction

Early exposure of medical students to surgical skills has been associated with an increased interest in pursuing a career in surgery. This study aimed to investigate the impact of student background on basic laparoscopic skills acquisition and perceived stress to workload during simulation.

Method

Students were recruited to a course modelled on the European Basic Laparoscopic Urological Skills (E-BLUS) programme. Students filled out a pre-course demographic survey, and a post-course survey that evaluated perceived stress to workload (SURG-TLX). Pre- and post-course confidence in laparoscopic skills, performance in the course, as well as SURG-TLX parameters were statistically compared for all demographic factors.

Result

Twenty-three participants completed the course, fifteen (65%) of which were female. Ten students were junior (first and second year), and thirteen were senior (third year and above). Hobbies were grouped into either requiring hand-eye coordination (n=9), manual dexterity (n=9), or no relevance to surgery (n=5). No significant differences were found in demographic factors for course performance or pre- and post-course confidence. No significant differences were found between male and female students, and between different hobby groups, in all SURG-TLX parameters. Senior students reported a significantly higher Physical Demand of the SURG-TLX compared to juniors (p=0.042). No differences were found in other parameters.

Conclusion

Our study showed no correlation between student background (notably sex and stage of medical school) and basic laparoscopic skills acquisition or stress during simulation. We therefore suggest that medical students are provided with more exposure to acquire basic laparoscopic skills regardless of their background.

Take-home message

Medical student background is not a discriminator in surgical simulation performance and stress. All medical students, regardless of their sex or stage of medical school, should be given the opportunity to practice laparoscopic skills.
O53: SO YOU WANT TO BE A ROBOTIC SURGEON? THE EFFECT OF BASELINE PSYCHOMOTOR ABILITY AND VIDEO-GAME EXPERIENCE ON ROBOTIC SURGICAL SKILL: A RANDOMISED CONTROL TRIAL
Authors: Hay D , Ahmed K , Dasgupta P , Challacombe B
Published: April 2021

Introduction

We assessed whether expert mentoring improved the rate of uptake of robotic surgical skill and whether general advanced psychomotor ability (PMA), and specific video-game experience (VGE) had any impact on robotic surgical skill.

Method

Twenty robotically naive medical students were blinded and randomised to two cohorts; control (CC) and intervention (IC). Each student's initial performance on a variety of da Vinci Skills Simulator (dVSSim) exercises was measured and then reassessed following an independent practice (CC) or mentor guided practice session (IC). Outcome metrics were overall score, time to completion, economy of motion and master workspace range. Quantitative, questionnaire data was collected to evaluate the relationship between robotic surgical skill, PMA and VGE. Statistical analysis was performed with SPSS software utilising the independent t-test.

Result

On average, overall score for CC improved by 16.8% compared to 43.3% for the IC (p=0.04). Time to completion improved by 26.2% (CC) vs. 40% (IC), economy of motion by 16.5% vs. 25% and master workspace range by 8% vs. 11%. PMA correlated with better initial performances for all metrics, especially for overall score (p=0.003) and economy of motion (p=0.03). Students with more VGE had overall scores that were on average 20% better than those with little or no experience and this relationship was also seen for economy of motion and master workspace range.

Conclusion

Expert mentoring leads to a greater improvement in performance than independent practice alone. Advanced PMA correlates with greater innate robotic skill, as does VGE, but to a lesser extent.

Take-home message

1) Expert mentoring leads to a greater improvement in performance than independent practice alone. 2) Advanced PMA correlates with greater innate robotic skill, as does VGE, but to a lesser extent.
O55: FOSTERING A CULTURE OF INNOVATION IN MEDICAL STUDENTS AS FUTURE SURGEONS
Authors: Sawhney R , Kenner M , Bolton W
Published: April 2021

Introduction

In recent years, new technologies and rising costs in the NHS have created a thirst for innovation, particularly in surgical specialties. Centres for medical education are being encouraged to cultivate enterprise and innovative thinking among their students.

A one-day educational conference was organised by a student-led surgical society to introduce students to technological advancements in surgery and underline the scope for innovation within the NHS.

Method

The conference included: three keynote speeches, surgical skills workshops (basic and advanced suturing, plastics and general surgery-oriented skills), 3D-printing demonstration, minimally-invasive surgery simulation, virtual reality interaction and an innovation ‘hack-a-thon’ addressing an unmet need in surgery.

An online questionnaire comprising Likert-scale and free-text responses was circulated to all attendees.

Result

72 delegates attended and 63 completed feedback forms (87.5%). As a consequence of attending the conference, participants reported an increase in interest in surgical careers (4.40-4.68, p <0.001), inspiration to innovate (3.77-4.21, p <0.001), and ability to innovate (3.69-4.06, p <0.001) before and after attending. Furthermore, 89% of delegates saw more scope for innovation in the NHS as a result of attending the conference. Finances and cultural attitudes resisting change were identified as major barriers to innovation; necessity for innovation (cost-cutting, improving patient outcomes and quality of life) was the primary driver.

Conclusion

This event had a significant impact on fostering innovative thinking among medical students. From the results, interventions listed above are meaningful in encouraging a culture of innovation among future surgeons.

Take-home message

This student-led conference had a positive impact on fostering innovative thinking among medical students. From the results, interventions such as inspiring talks, interactive skills workshops, and hack-a-thons can be meaningful tools for encouraging a culture of innovation among future surgeons.
O56: THE TREND OF SURGICAL PUBLICATIONS IN THE UNITED KINGDOM OVER THE LAST 10 YEARS
Authors: Kwan LYA , Chan J
Published: April 2021

Introduction

Research plays an important role in the surgical field. It has been deemed to be the keystone on the progression of surgical care and the introduction of new directions in surgery. We aimed to evaluate the output of UK surgeons in ten high impact factor surgical journals over the last three decades.

Method

Ten surgical journals were selected and investigated, based on 1997,2007, and 2017 journal impact factors. All articles that have contributed academically were examined, these included: original research articles, meta-analysis, debate articles, case reports and studies.

Result

The number of total publications from the ten journals has increased by 35.4% (from 2403 papers in 2007 to 3722 papers in 2017). The number of papers from these journals from the UK has increased by 19.5% (63 papers), however, the percentage output when compared to other regions, has decreased by 2.1% from 10.8% in 2007 to 8.7% in 2017. The USA remains to have the greatest contribution.

Conclusion

The result shows a decline in the percentage output of the UK when compared to other countries. This result aligns with other studies published. Focus should be made on improving the current situation of academic medicine in the UK.

Take-home message

There is a decline in the percentage output of the UK when compared to other countries. Focus should be made on improving the current situation of academic medicine in the UK.
O61: TEXTBOOK SURGICAL OUTCOMES IN OESOPHAGO-GASTRIC CANCER: THE INFLUENCE OF NATIONAL KEY PERFORMANCE INDICATORS
Authors: Al Azzawi M , Bolger JC , Bolger EM , Whooley J , Allen J , Trench L , Downey E , Arumugasamy M , Robb WB
Published: April 2021

Introduction

High quality surgery remains the cornerstone of treating oesophago-gastric malignancy. Recent work from the Dutch Upper-gastrointestinal Cancer Audit (DUCA) have defined ten surgical and perioperative ‘textbook’ parameters that correlate with improved overall survival. The aim of this project was to examine the proportion of patients attaining ‘textbook’ outcomes for oesophagectomy and gastrectomy in our unit before and after the introduction of national key performance indicators (KPIs).

Method

A retrospective review of all oesophagectomies and gastrectomies from January 2010 until June 2019 was performed. Clinical, pathological, perioperative, morbidity and mortality outcomes were recorded. 10 ‘textbook’ parameters were studied pre- and post-KPI introduction.

Result

269 and 284 patients underwent oesophagectomy and gastrectomy respectively, 167 pre-KPI and 386 post-KPI. There were no significant differences in age (67.6 vs 66.4 years, p=0.6), gender (71% male, 29% female vs 68% male, 22% female, p=0.48), ASA grade (p=0.6) or tumour stage (p=0.37) pre- and post-KPI. In the pre-KPI era, 28/167 (17%) patients achieved all ten textbook parameters, compared with 157/386, (41%, p=0.001) post-KPI. This compares favourably to DUCA ‘textbook’ data. There was an improvement in adequate lymphadenectomy (56% vs 83%, p=0.002), a reduction in margin positivity (21% vs 7%, p= 0.001) and peri-operative mortality (6% vs 2%, p=0.03) post-KPI.

Conclusion

There has been a significant improvement in perioperative outcomes in esophagectomy following the introduction of national KPIs in our unit. The number of patients achieving ‘textbook’ outcomes is comparable with international standards. The identification of textbook parameters allows further focus for future quality improvement initiatives.

Take-home message

National KPIs improve peri-operative outcomes in oesophago-gastric cancer.
O68: REDUCING VENOUS CONGESTION FOLLOWING LOWER LIMB RECONSTRUCTION WITH ISOMETRIC CALF EXERCISES: A PROSPECTIVE CLINICAL STUDY
Authors: Geoghegan L , Kwasnicki RM , Henton JM , Hettiaratchy S , Jain A
Published: April 2021

Introduction

Early post-operative dependency aids healing following lower limb reconstruction although increases venostasis and reduces perfusion in the acute setting. The commonest cause of lower limb flap failure is venous congestion and external compression with stockings and pneumatic devices is contraindicated. The aim of this clinical study was to determine whether venous congestion could be reduced through patient-led isometric contractions following lower limb reconstruction.

Method

A single centre prospective clinical study was conducted at St. Marys Hospital, Imperial College NHS Trust. Combined tissue photospectroscopy and laser Doppler (O2C, LEA, Germany) was used to assess superficial oxygen saturation, venous congestion and flow during standardised training regimens. Haemodynamic parameters were collected in an acute post-operative and outpatient rehabilitation cohort.

Result

In the acute post-operative cohort, isometric contractions failed to improve superficial flow following dependency on the post-operative day (POD) one (-44% ± 8). Isometric contractions improved superficial flow from POD5 (+11% ± 102) although venous congestion remained higher than measurements taken during rest (+32% ± 54). In the outpatient rehabilitation cohort isometric contractions significantly increased superficial flow following dependency (+16% ± 33, p=0.01) at a mean of 14 weeks since discharge.

Conclusion

This study provides objective physiological evidence of the haemodynamic changes that occur with dependency and isometric contraction following lower limb reconstruction. These physiological changes evolve following extremity reconstruction and it appears that a continued healing effect exists to accommodate progressive changes in flow dynamics. The present findings could be used to inform enhanced recovery programmes following limb reconstruction.

Take-home message

Simple patient-led calf contractions reduce venous congestion and improve cutaneous flow following lower extremity reconstruction.
O71: INTRA-OPERATIVE SPINAL CORD MONITORING DURING SPINAL SURGERY: DOES IT HAVE ANY CLINICAL VALUE?
Authors: Murphy B , McCabe JP
Published: April 2021

Introduction

Spinal cord surgery is a technically challenging endeavour with potentially devastating complications for patients and surgeons. Spinal cord monitoring (SCM), is one method of preventing and identifying damage to the spinal cord. At present, indications for its use are based more on individual surgeon preference and for medico legal purposes. Our study aimed to determine SCM's utility as a clinical tool.

Method

This is a retrospective case series of 169 patients who underwent spinal surgery with SCM at two institutions between 2013 and 2018. Signal changes detected were recorded as well as the surgeon's response to these changes. Patients were followed up to one-year post-surgery using our institution's EVOLVE system. The main outcome measure in this study was new post-operative neurological signs and/or symptoms and what effect, if any, IONM and subsequent surgeon intervention had on these complications.

Result

Indications for SCM included cervical stenosis, cervical disc prolapse, unstable fractures and bony metastases. Signal changes were observed in 33% (n=55) of cases. 24 of these patients responded to re-positioning. There were 7 total complications with full resolution by 12 months. False negative rate was 2.4% (n=4). There was one true positive. The largest cohort of patients included those who experienced no signal changes and subsequently no post-operative deficits (n=124).

Conclusion

SCM is a non-invasive clinical tool that may be utilised for medicolegal reasons. Its use as a clinical tool is questionable given its relatively high false negative rate and low false positive rate.

Take-home message

Spinal cord monitoring may be used by spinal surgeons for medicolegal reasons if desired. Its use as a clinical tool is questionable at best.
O74: ASSESSING THE USEFULNESS OF THREE-DIMENSIONAL IMAGING AND VIRTUAL REALITY IN SURGICAL PLANNING: A MEDICAL STUDENT LED PILOT STUDY
Authors: Ryan C , O'Malley E , Sheppard D
Published: April 2021

Introduction

Nephron-sparing surgery is becoming more common as surgical techniques advance. VR and 3D visualisation appear to provide better anatomical understanding in presurgical planning than two-dimensional alone. 3D models may enable greater tissue salvation and fewer complications. 3D model preparation and advancing research is expensive and time consuming. We aim to pilot study led by medical student, create reliable anatomical kidney models and assess usefulness in surgical planning.

Method

Routine CT urograms were performed on 128 slice scanner using split bolus technique. Medical student segmented and displayed models in VR using 3DSlicer. Radiology registrar and consultant validated models. Two urology surgeons completed qualitative questionnaires.

Result

We included two patients. Only minor segmentation tweaks by radiologist ensured accurately demonstrated tumors. Tissue contrast quality varied between CT scans complicating segmentation. Both surgeons deemed models helpful in visualising hilar anatomy, predicting bleeding complications, determining laparoscopic/open and partial/full nephrectomy approach. Surgeons prioritised vasculature visualisation over collecting system. Surgeons suggested gauging tumor depth would be useful. Considering 3D printing cost, surgeons agreed VR alone may suffice.

Conclusion

Surgeons found 3D and VR enabled accurate surgical planning and patient counselling regarding nephrectomy risk. Minor CT protocol recommendations enable easier and more accurate segmentation, without increasing patient's radiation exposure. Annual leave during 8-week summer project reflects case numbers. Since, we've identified more cases to assess surgical parameters against matched cohort. We've begun work for adrenal surgery. It's feasible for medical students with minimal surgical/radiological knowledge to advance this research, gaining valuable experience.

Abbrev

Virtual Reality(VR), Three-dimensional(3D), Computerised Tomography(CT)

Take-home message

Three-dimensional imaging and virtual reality may improve surgical planning and patient counselling. Regarding nephrectomy, this could give surgeons the confidence to convert from full nephrectomy to partial nephrectomy approach, improving patient outcome.
O76: SERUM JAM-A AS A PREDICTOR OF TREATMENT RESISTANCE IN BREAST CANCER PATIENTS
Authors: Rutherford EJ , Richards CE , Leech AO , Hill ADK , Hopkins AM
Published: April 2021

Introduction

Junctional Adhesion Molecule-A (JAM-A) has important physiological functions in epithelial and endothelial barriers, but its overexpression has also been linked with tumour progression and poor prognosis in various malignancies. Since JAM-A can be enzymatically cleaved (cJAM-A) and has been detected in the bloodstream, we hypothesized that cJAM-A shed from tumours overexpressing JAM-A may represent a possible predictor of treatment resistance in breast cancer.

Method

An assay was optimised to detect cJAM-A in serum/plasma. Samples were obtained from HER2-positive breast cancer patients (n=20) in Beaumont Hospital. Independently, serial samples were obtained from a Canadian cohort of locally advanced breast cancer (LABC) patients (n=53).

Result

Serum cJAM-A levels in therapy-resistant patients was significantly higher than those in treatment-sensitive patients (p<0.05) in an Irish cohort of HER2 positive patients. In a diverse international cohort of LABC patients, the development of metastatic disease was associated with higher levels of cJAM-A (p<0.05) as well as shorter time to progression (p<0.05).

Conclusion

Our data suggest that cJAM-A merits further investigation as a novel biomarker enabling prospective identification of patients at greatest risk of developing therapeutic resistance.

Take-home message

Our data suggest that cJAM-A merits further investigation as a novel biomarker enabling prospective identification of patients at greatest risk of developing therapeutic resistance.