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ObjectiveTo determine the rates of asymptomatic viral carriage and seroprevalence of SARS-CoV-2 antibodies in healthcare workers.DesignA cross-sectional study of asymptomatic healthcare workers undertaken on 24/25 April 2020.SettingUniversity Hospitals Birmingham NHS Foundation Trust (UHBFT), UK.Participants545 asymptomatic healthcare workers were recruited while at work. Participants were invited to participate via the UHBFT social media. Exclusion criteria included current symptoms consistent with COVID-19. No potential participants were excluded.InterventionParticipants volunteered a nasopharyngeal swab and a venous blood sample that were tested for SARS-CoV-2 RNA and anti-SARS-CoV-2 spike glycoprotein antibodies, respectively. Results were interpreted in the context of prior illnesses and the hospital departments in which participants worked.Main outcome measureProportion of participants demonstrating infection and positive SARS-CoV-2 serology.ResultsThe point prevalence of SARS-CoV-2 viral carriage was 2.4% (n=13/545). The overall seroprevalence of SARS-CoV-2 antibodies was 24.4% (n=126/516). Participants who reported prior symptomatic illness had higher seroprevalence (37.5% vs 17.1%, χ2=21.1034, pConclusions and relevanceWe identify differences in the occupational risk of exposure to SARS-CoV-2 between hospital departments and confirm asymptomatic seroconversion occurs in healthcare workers. Further investigation of these observations is required to inform future infection control and occupational health practices.

Introduction: Tumor specific MHC class II (tsMHC-II) expression impacts tumor microenvironmental immunity. tsMHC-II positive cancer cells act as surrogate antigen presenting cells and targets for CD4+ T cell-mediated lysis. In colorectal cancer (CRC), tsMHC-II negativity is common and in cell lines is attributable to CIITA promoter methylation. To clarify mechanisms of tsMHC-II repression in CRC we analyzed CRC organoids which are epigenetically faithful to tissue of origin. Methods: 15 primary CRC organoids were treated with IFNγ +/- epigenetic modifiers. Flow cytometry was used to assess for tsMHC-II inducibility. RT-qPCR, total RNAseq, nanopore sequencing, bisulfite conversion/pyrosequencing and western blotting were used to quantitate CIITA, STAT1, IRF1 and JAK1 expression, gene structure and promoter methylation and ChIP-PCR to quantitate H3K9ac, H3K9Me2 and EZH2 occupancy at CIITA. Results: We define three types of tsMHC-II response to IFNγ in CRC: strong- (≥50%), delayed/weak- (11-49%) and non-inducibility (≤10%). 8/15 demonstrated strong expression, 4/15 delayed/weak: although it was possible to overcome this weak expression with prolonged IFNγ exposure in 3/15 without additional pharmacological treatment. In 1/15 organoid, expression was restricted even with prolonged exposure due to IFNγ-mediated EZH2 occupancy at CIITA: tsMHC-II expression was enhanced by EZH2 and HDAC inhibition. Non-inducibility is seen in 3 CMS1 organoids due to JAK1 mutation. These demonstrated low level (11%) JAK1 promoter methylation, but tsMHC-II inducibility was not rescued with DNMT inhibition. No organoid demonstrated CIITA promoter methylation, despite confirming the presence in previously described 2D cell lines, suggesting this is acquired through culture methods and not reflective of disease biology. Conclusion: We demonstrate using epigenetically appropriate models the individual variation in pharmacologic tractability of epigenetic modification in CRC. Providing IFNγ signaling is intact, most CRC organoids are class II inducible. Up-regulation of restricted tsMHC-II through targeted epigenetic therapy is seen in 1/15 organoid. These data may explain some of the disappointing results of immuno-epigenetic approaches in the clinic. Citation Format: Oliver J. Pickles, Kasun Wanigasooriya, Anetta Ptasinska, Akshay J. Patel, Helen L. Robbins, Claire Bryer, Celina M. Whalley, Louise Tee, Neeraj Lal, Maria Pinna, Nahla Elzefzafy, Phillipe Taniere, Andrew D. Beggs, Gary W. Middleton. Colorectal cancer displays three patterns of tumor-specific MHC-II inducibility and dynamics, with implications for combining epigenetic therapy with immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2989.

Background COVID-19 has a significant impact on elective surgery for benign disease. When routine services resumed in April 2021, surgeons were faced with higher number of complicated cases. The aim of this study is to examine the effect of COVID-19 related delays on the outcomes of patients undergoing elective laparoscopic cholecystectomy (LC) in an upper gastrointestinal unit in the UK. Methods Data were collected retrospectively on consecutive patients undergoing elective LC between 1/3/19 to 1/5/19 (Pre-COVID) and 1/4/21 to 11/6/21 (resumption of elective operating following COVID). The indications for surgery, intraoperative details, postoperative complications, length of stay (LoS) and 30- day readmission were compared between the two cohorts. We divided indications for surgery as inflammatory (acute cholecystitis, gallstone pancreatitis, CBD stone with cholangitis) vs non-inflammatory (biliary colic, gallbladder polyps, CBD stone without cholangitis). Data were analysed using the Mann-Whitney U-test and Chi-square or Fisher’s exact test. A p value of Results 159 patients were analysed, 106 in Pre-COVID vs 53 in Post-COVID. Both cohorts had similar age, gender, ASA-grade, BMI. 68 (64.2%) of the pre-COVID cohort were operated for a non-inflammatory pathology compared to 19(35.8%) of the post-COVID cohort (p Conclusions Surgery in the post-COVID cohort was associated with a higher incidence of inflammatory biliary disease, subtotal cholecystectomy and procedure abandoned. Although the numbers in our study are small they highlight the need for enhanced preoperative assessment in elective biliary surgery as the NHS emerges from the acute phase of the pandemic.

Gallbladder torsion is a rare cause of acute abdominal pain and can be a diagnostic challenge for the general surgeon. We herein present a case of an 81-year-old man who presented with right-sided abdominal pain and signs of intra-abdominal infection. Transabdominal ultrasound, computed tomography (CT) and magnetic resonance cholangio-pancreatography (MRCP) scans could not identify with certainty the underlying cause of the symptoms and eventually the patient underwent a diagnostic laparoscopy, which revealed the presence of gallbladder torsion. Sequentially, a laparoscopic cholecystectomy was performed in a standard fashion and the patient had an uneventful post-operative recovery. Our case highlights the importance of diagnostic laparoscopy as a diagnostic and treatment tool in unclear cases of acute abdomen. J Curr Surg. 2020;10(3):28-31 doi: https://doi.org/10.14740/jcs405

Partial or total resistance to preoperative chemoradiotherapy occurs in more than half of locally advanced rectal cancer patients. Several novel or repurposed drugs have been trialled to improve cancer cell sensitivity to radiotherapy, with limited success. To understand the mechanisms underlying this resistance and target them effectively, we initially compared treatment-naive transcriptomes of radiation-resistant and radiation-sensitive patient-derived organoids (PDO) to identify biological pathways involved in radiation resistance. Pathway analysis revealed that PI3K/AKT/mTOR and epithelial mesenchymal transition pathway genes were upregulated in radioresistant PDOs. Moreover, single-cell sequencing of pre & post-irradiation PDOs showed mTORC1 upregulation, which was confirmed by a genome-wide CRSIPR-Cas9 knockout screen using irradiated colorectal cancer (CRC) cell lines. Based on these findings, we evaluated cancer cell viability in vitro when treated with radiation in combination with dual PI3K/mTOR inhibitors apitolisib or dactolisib. Significant AKT phosphorylation was detected in HCT116 cells two hours post-irradiation (p=0.027). Dual PI3K/mTOR inhibitors radiosensitised HCT116 and radiation-resistant PDO lines. The PI3K/AKT/mTOR pathway upregulation contributes to radioresistance and its pharmacological inhibition leads to significant radiosensitisation in an organoid model of CRC and is a target for clinical trials.

Background:The Covid-19 pandemic led to significant changes and disruptions to medical education worldwide. We evaluated medical student perceived views on training, their experiences and changes to teaching methods during the pandemic.MethodsAn online survey of medical students was conducted in the Autumn of 2020. An international network of collaborators facilitated participant recruitment. Students were surveyed on their perceived overall impact of Covid-19 on their training and several exposure variables. Univariate analyses and adjusted multivariable analysis were performed to determine strengths in associations.ResultsA total of 1604 eligible participants from 45 countries took part in this survey and 56.3% (n=860) of these were female. The median age was 21 (Inter Quartile Range:21-23). Nearly half (49.6%, n=796) of medical students were in their clinical years. The majority (n=1356, 84.5%) were residents of a low or middle income country. A total of 1305 (81.4%) participants reported that the Covid-19 pandemic had an overall negative impact on their training. On adjusted analysis, being 21 or younger, females, those reporting a decline in conventional lectures and ward based teaching were more likely to report an overall negative impact on their training (p≤0.001). However, an increase in clinical responsibilities was associated with lower odds of participants reporting a negative impact on training (ppConclusionMedical students reported an overall significant negative impact of the Covid-19 pandemic on their undergraduate training. The efficacy of novel virtual methods of teaching to supplement traditional teaching methods warrants further research.

Introduction The COVID-19 pandemic has resulted in a significant burden on healthcare systems causing disruption to medical and surgical training of doctors globally. Aims and objectives This is the first international survey assessing the perceived impact of the COVID-19 pandemic on training of doctors of all grades and specialties. Methods An online global survey was disseminated using Survey Monkey® between 4th August 2020 and 17th November 2020. A global network of collaborators facilitated participant recruitment. Data was collated anonymously with informed consent and analysed using univariate and adjusted multivariable analysis. Results 743 doctors of median age 27 (IQR: 25-30) were included with the majority (56.8%, n=422) being male. Two-thirds of doctors were in a training post (66.5%, n=494), 52.9% (n=393) in a surgical specialty and 53.0% (n= 394) in low- and middle-income countries. 69.2% (n=514) reported an overall perceived negative impact of the COVID-19 pandemic on their training. A significant decline was noted among non-virtual teaching methods such as face-to-face lectures, tutorials, ward-based teaching, theatre sessions, conferences, simulation sessions and morbidity and mortality meetings (p≤0.05). Doctors from low or middle-income countries were associated with perceived inadequate supervision while performing invasive procedures under general, local or regional anaesthetic. (p≤0.05) Conclusion In addition to the detrimental impact of the COVID-19 pandemic on healthcare infrastructure, there has been an indirect consequence of disrupted training within medical and surgical subspecialties. A focus on reconfiguration of training programs through a variety of additional resources will become imperative to reduce the long-term sequalae of COVID-19 on doctors’ training.

Supplemental material, sj-pdf-1-mde-10.1177_2382120520984184 for The Effectiveness of a Foundation Year 1 Doctor Preparation Course for Final Year Medical Students by William Beedham, Kasun Wanigasooriya, Georgia R Layton, Ley Taing Chan, Adnan Darr and Devender Mittapalli in Journal of Medical Education and Curricular Development

Background The coronavirus disease 2019 (COVID-19) pandemic is likely to lead to a significant increase in mental health disorders among healthcare workers (HCW). Aims We evaluated the rates of anxiety, depressive and post-traumatic stress disorder (PTSD) symptoms in a population of HCW in the UK. Method An electronic survey was conducted between the 5 June 2020 and 31 July 2020 of all hospital HCW in the West Midlands, UK using clinically validated questionnaires: the 4-item Patient Health Questionnaire(PHQ-4) and the Impact of Event Scale-Revised (IES-R). Univariate analyses and adjusted logistic regression analyses were performed to estimate the strengths in associations between 24 independent variables and anxiety, depressive or PTSD symptoms. Results There were 2638 eligible participants who completed the survey (female: 79.5%, median age: 42 years, interquartile range: 32–51). The rates of clinically significant symptoms of anxiety, depression and PTSD were 34.3%, 31.2% and 24.5%, respectively. In adjusted analysis a history of mental health conditions was associated with clinically significant symptoms of anxiety (odds ratio (OR) = 2.3, 95% CI 1.9–2.7, P < 0.001), depression (OR = 2.5, 95% CI 2.1–3.0, P < 0.001) and PTSD (OR = 2.1, 95% CI 1.7–2.5, P < 0.001). The availability of adequate personal protective equipment (PPE), well-being support and lower exposure to moral dilemmas at work demonstrated significant negative associations with these symptoms (P ≤ 0.001). Conclusions We report higher rates of clinically significant mental health symptoms among hospital HCW following the initial COVID-19 pandemic peak in the UK. Those with a history of mental health conditions were most at risk. Adequate PPE availability, access to well-being support and reduced exposure to moral dilemmas may protect hospital HCW from mental health symptoms.

BackgroundThe Covid-19 pandemic is likely to lead to a significant increase in mental health disorders amongst healthcare workers (HCW).AimsWe evaluated the prevalence of anxiety, depressive and post-traumatic stress disorder (PTSD) symptoms in a HCW population in the United Kingdom (UK), to identify subgroups most at risk.MethodsAn electronic survey was conducted between the 05/06/2020 and 31/07/2020 of all hospital HCW in the West Midlands, UK using clinically validated questionnaires: Patient Health Questionnaire-4 (PHQ-4) and the Impact of Event Scale-Revised (IES-R). Univariate analyses and adjusted logistic regression analyses were performed to estimate the strengths in associations.ResultsThere were 2638 eligible participants who completed the survey (female: 79.5%, median age: 42 [IQR: 32-51] years). The prevalence rates of clinically significant symptoms of anxiety, depression and PTSD were 34.3%, 31.2% and 24.5% respectively. In adjusted analysis a history of mental health conditions was associated with clinically significant symptoms of anxiety (odds ratio 2.3 [95% CI 1.9–2.7]; pppp≤0.001).ConclusionsWe report a high prevalence of clinically significant symptoms of anxiety, depression and PTSD in hospital HCW following the initial Covid-19 pandemic peak in the UK. Those with a history of mental health conditions were most at risk. Adequate PPE availability, access to wellbeing support and reduced exposure to moral dilemmas may protect hospital HCW from mental health symptoms.

BackgroundStarting work as a junior doctor can be daunting for any medical student. There are numerous aspects of the hidden or informal curriculum which many students fail to acquire during their training.ObjectivesTo evaluate the effectiveness of a novel foundation year one (FY1) doctor preparation course focusing on certain core topics, practical tips and components of the hidden curriculum. The primary objective was to improve the confidence level and knowledge of final year medical student transition to FY1 doctors.MethodA two-day, practical course titled “Preparation 2 Practice” delivering hands-on, small-group and lecture-based teaching, covering core medical student undergraduate curriculum topics in medicine and surgery. The course content spanned therapeutics, documentation skills and managing acute clinical tasks encountered by FY1 doctors during an on-call shift. A pre- and post-course survey and knowledge assessment were carried out to assess the effectiveness of the course. The assessment was MCQ-based, derived from topics covered within our course. The 20-question test and a short survey were administered electronically.ResultsTwenty students from a single UK medical school attended the course. 100% participation was observed in the pre- and post-course test and survey. The median post-course test result was 22 (IQR 20.25 –23.75) which was higher than the median pre course test score of 18.75 (IQR 17–21.75). A Wilcoxon sign rank test revealed a statistically significant difference between the pre- and post-course test results (p=0.0003). The self-reported confidence score of delegates on starting work as a junior doctor was also significantly higher following the course (p=0.004).ConclusionThe results show a significant improvement in perceived confidence and knowledge on core curriculum topics amongst final year medical students having attended our FY1 doctor preparation course. We conclude that there is scope for similar supplementary courses as an adjunct to the undergraduate medical curriculum.

Background The correlates of protection against SARS-CoV-2 and their longevity remain unclear. Studies in severely ill individuals have identified robust cellular and humoral immune responses against the virus. Asymptomatic infection with SARS-CoV-2 has also been described, but it is unknown whether this is sufficient to produce antibody responses. Methods We performed a cross-sectional study recruiting 554 health care workers from University Hospitals Birmingham NHS Foundation Trust who were at work and asymptomatic. Participants were tested for current infection with SARS-CoV-2 by nasopharyngeal swab for real-time polymerase chain reaction and for seroconversion by the measurement of anti-SARS-CoV-2 spike glycoprotein antibodies by enzyme linked immunosorbent assay. Results were interpreted in the context of previous, self-reported symptoms of illness consistent with COVID-19. Results The point prevalence of infection with SARS-CoV-2, determined by the detection of SARS-CoV-2 RNA on nasopharnygeal swab was 2.39% (n=13/544). Serum was available on 516 participants. The overall rate of seroconversion in the cohort was 24.4% (n=126/516). Individuals who had previously experienced a symptomatic illness consistent with COVID-19 had significantly greater seroconversion rates than those who had remained asymptomatic (37.5% vs 17.1%, χ2 =21.1034, p Conclusions In a large cross-sectional seroprevalence study of health-care workers, we demonstrate that asymptomatic seroconversion occurs, however prior symptomatic illness is associated with quantitatively higher antibody responses. The identification that the potential for seroconversion in health-care workers can associate differentially with certain hospital departments may inform future infection control and occupational health practices. Research in context Evidence before the study To date, no study has examined the cross-sectional seroprevalence of anti-SARS-CoV-2 antibodies in health care workers during the COVID-19 pandemic. Existing evidence suggests that the levels of SARS-CoV-2 antibodies developing following infection may vary with disease severity in keeping with previous coronavirus pandemics. Added value of this study We demonstrate that seroconversion can occur in health care workers who have suffered no previous symptoms of SARS-Cov-2 infection. However, prior symptomatic infection tends to drive quantitatively superior antibody responses against the virus. We observed differential seroconversion rates in individuals working within different hospital departments. Using intensive care as a reference, the relative risk for seroconversion was greatest for those working in housekeeping, acute and general internal medicine. Implications of all the available evidence Insight into the current seroprevalence of SARS-CoV-2 antibodies within a high-risk cohort of health-care workers is of direct relevance as a reference point for future community serological surveys. We provide further evidence of asymptomatic infection and seroconversion, strengthening the argument for regular, routine screening of health-care workers. Finally, we provide evidence that individuals working in particular roles within the NHS are at greater risk of seroconversion with significant implications for their occupational health.

Background In January 2020 reports of unidentified severe respiratory illness were described in Wuhan, China. A rapid expansion in cases affecting most countries around the globe led to major changes in the way people live their daily lives. In the United Kingdom, the Department of Health and Social Care directed healthcare providers to establish additional resources to manage the anticipated surge in cases that could overwhelm the health services. A priority area was testing for SARS-CoV-2 RNA and its detection by qualitative RT-PCR. Design A laboratory workflow twinning research environment with clinical laboratory capabilities was implemented and validated in the University of Birmingham within 4 days of the project initiation. The diagnostic capability was centred on an IVD CE-marked RT-PCR kit and designed to provide surge capacity to the nearby Queen Elizabeth Hospital. The service was initially tasked with testing healthcare workers (HCW) using throat swabs, and subsequently the process investigated the utility of using saliva as an alternative sample type. Results Between the 8th April 2020 and the 30th April 2020, the laboratory tested a total of 1282 HCW for SARS-CoV-2 RNA in throat swabs. RNA was detected in 54 % of those who reported symptoms compatible with COVID-19, but in only 4% who were asymptomatic. Conclusion This capability was established rapidly and utilised a cold-chain free methodology, applicable to a wide range of settings, and which can provide surge capacity and support to clinical laboratories facing increasing pressure during periods of national crisis.

Radiotherapy is routinely used as a neoadjuvant, adjuvant or palliative treatment in various cancers. There is significant variation in clinical response to radiotherapy with or without traditional chemotherapy. Patients with a good response to radiotherapy demonstrate better clinical outcomes universally across different cancers. The PI3K/AKT/mTOR pathway upregulation has been linked to radiotherapy resistance. We reviewed the current literature exploring the role of inhibiting targets along this pathway, in enhancing radiotherapy response. We identified several studies using in vitro cancer cell lines, in vivo tumour xenografts and a few Phase I/II clinical trials. Most of the current evidence in this area comes from glioblastoma multiforme, non-small cell lung cancer, head and neck cancer, colorectal cancer, and prostate cancer. The biological basis for radiosensitivity following pathway inhibition was through inhibited DNA double strand break repair, inhibited cell proliferation, enhanced apoptosis and autophagy as well as tumour microenvironment changes. Dual PI3K/mTOR inhibition consistently demonstrated radiosensitisation of all types of cancer cells. Single pathway component inhibitors and other inhibitor combinations yielded variable outcomes especially within early clinical trials. There is ample evidence from preclinical studies to suggest that direct pharmacological inhibition of the PI3K/AKT/mTOR pathway components can radiosensitise different types of cancer cells. We recommend that future in vitro and in vivo research in this field should focus on dual PI3K/mTOR inhibitors. Early clinical trials are needed to assess the feasibility and efficacy of these dual inhibitors in combination with radiotherapy in brain, lung, head and neck, breast, prostate and rectal cancer patients.

Retroperitoneal liposarcomas are rare tumours that carry a poorer prognosis than their extremity counterparts. Within their subtypes - well differentiated (WDL), dedifferentiated (DDL), myxoid (MLS) and pleomorphic (PLS) - they exhibit a diverse genomic landscape. With recent advances in next generation sequencing, the number of studies exploring this have greatly increased. The recent literature has deepened our understanding of the hallmark MDM2/CDK4 amplification in WDL/DDL and addressed concerns about toxicity and resistance when targeting this. The FUS-DDIT3 fusion gene remains the primary focus of interest in MLS with additional potential targets described. Whole genome sequencing has driven identification of novel genes and pathways implicated in WDL/DDL outside of the classic 12q13-15 amplicon. Due to their rarity; anatomical location and histologic subtype are infrequently mentioned when reporting the results of these studies. Reports can include non-adipogenic or extremity tumours, making it difficult to draw specific retroperitoneal conclusions. This narrative review aims to provide a summary of retroperitoneal liposarcoma genomics and the implications for therapeutic targeting.

Background The Covid-19 pandemic is likely to lead to a significant increase in mental health disorders amongst healthcare workers (HCW). Aims We evaluated the prevalence of anxiety, depressive and post-traumatic stress disorder (PTSD) symptoms in a HCW population in the United Kingdom (UK), to identify subgroups most at risk. Methods An electronic survey was conducted between the 05/06/2020 and 31/07/2020 of all hospital HCW in the West Midlands, UK using clinically validated questionnaires: Patient Health Questionnaire-4 (PHQ-4) and the Impact of Event Scale-Revised (IES-R). Univariate analyses and adjusted logistic regression analyses were performed to estimate the strengths in associations. Results There were 2638 eligible participants who completed the survey (female: 79.5%, median age: 42 [IQR: 32-51] years). The prevalence rates of clinically significant symptoms of anxiety, depression and PTSD were 34.3%, 31.2% and 24.5% respectively. In adjusted analysis a history of mental health conditions was associated with clinically significant symptoms of anxiety (odds ratio 2.3 [95% CI 1.9–2.7]; p Conclusions We report a high prevalence of clinically significant symptoms of anxiety, depression and PTSD in hospital HCW following the initial Covid-19 pandemic peak in the UK. Those with a history of mental health conditions were most at risk. Adequate PPE availability, access to wellbeing support and reduced exposure to moral dilemmas may protect hospital HCW from mental health symptoms.

Esophagectomy is a mainstay in curative treatment for esophageal cancer; however, the reported techniques and outcomes can vary greatly. Thirty-day mortality of patients with an intact anastomosis is 2-3% as compared to 17-35% in patients who have an anastomotic leak. The subsequent management of leaks postesophagectomy has great global variability with little consensus on a gold standard of practice. The aim of this multicentre prospective audit is to analyze current techniques of esophagogastric anastomosis to determine the effect on the anastomotic leak rate. Leak rates and leak management will be assessed to determine their impact on patient outcomes. A 12-month international multicentre prospective audit started in April 2018 and is coordinated by a team from the West Midlands Research Collaborative. This will include patients undergoing esophagectomy over 9 months and encompassing a 90-day follow-up period. A pilot data collection period occurred at four UK centers in 2017 to trial the data collection form. The audit standards will include anastomotic leak and the conduit necrosis rate should be less than 13% and major postoperative morbidity (Clavien-Dindo Grade III or more) should be less than 35%. The 30-day mortality rate should be less than 5% and the 90-day mortality rate should be less than 8%. This will be a trainee-led international audit of esophagectomy practice. Key support will be given by consultant colleagues and anesthetists. Individualized unit data will be distributed to the respective contributing sites. An overall anonymized report will be made available to contributing units. Results of the audit will be published in peer-reviewed journals with all collaborators fully acknowledged. The key information and results from the audit will be disseminated at relevant scientific meetings.

Malnutrition results in a significant increase in postoperative morbidity and mortality after abdominal surgery. Apart from the anthropometric assessments, malnutrition can be also assessed using laboratory scores, with the most widely used being Onodera's Prognostic Nutritional Index (PNI). The purpose of our study was to assess if the presence of malnutrition as calculated by the Onodera's PNI was associated with higher postoperative morbidity after elective colorectal cancer resection.We performed a retrospective analysis of our institutional database including the patients who underwent elective colorectal cancer resection over a 24-month period. PNI scores were calculated and correlated amongst other parameters, such as cancer stage, severity of postoperative complications, unplanned transfusion of blood products, need for unplanned level 2/3 care after surgery and overall length of hospitalization.A total of 213 patients were included in this analysis, with 22.5% being classified as malnourished based on the preoperative PNI. Of note, PNI values were inversely associated with advanced-stage disease, severity of postoperative complications and unplanned intensive care unit (ICU) admission postoperatively. Also, malnourished patients had a statistically significant prolonged length of in-hospital stay. No difference in PNI scores was identified between groups requiring unplanned blood products' transfusions.Preoperative malnutrition status as defined by PNI is associated with greater postoperative morbidity after elective surgery for colorectal cancer. Routine nutritional assessment and ad hoc nutritional support prior to surgery could contribute to an improvement of postoperative outcome after colorectal cancer resections.

Perioperative nutritional optimisation is one of the key aspects of the Enhanced Recovery after Surgery (ERAS) pathway after elective colorectal cancer resections. Despite the general acceptance of ERAS as a safe and cost-effective perioperative care bundle, significant variations in terms of nutritional support exist among colorectal units.To assess these variations, we performed a cross-sectional online survey among colorectal surgical residents within a UK region.Our survey of practice demonstrated that despite the international recommendations, a considerable percentage of colorectal units would still advocate prolonged fasting prior to surgery without routine use of carbohydrate loading, as well as delaying resumption of oral intake postoperatively. In addition, in almost one in five colorectal units, the patients would not be assessed by the specialist nutrition team for potential support during their hospitalisation.Therefore, we believe that further education of the medical and allied health professional staff is required regarding the correct implementation of ERAS pathway guidelines after elective surgery for colorectal cancer.

Background More than 70% of patients diagnosed with colorectal cancer with liver metastasis have unresectable disease, so the available treatment is systemic chemotherapy that has limited efficacy and causes harmful side-effects. Thus novel and more effective drugs are needed to improve patients’ survival and quality of life. Recent studies have identified several genomic alterations in CRLM that can theoretically be targeted by novel cancer-specific drugs. Among those is the gain-of-function mutations in PIK3CA – the gene encoding the p110a catalytic subunit of PI3K – that are present in 18% of metastatic colorectal tumours. Following the recent FDA-approval of Alpelisib (a PI3Ka-specific inhibitor) HR-positive breast cancer, there is increasing interest to test this drug efficacy to treat CRLM patients with PIK3CA mutations. Although widely used to test cancer cell response, immortalized cell lines fail to represent tumour genomic alterations and heterogeneity. Our goal is to develop patient-derived primary cell models that can be used to reliably test patients’ drug response. Methods Fresh colorectal cancer liver metastasis surgical specimens were dissociated and digested into single cells and seeded in matrigel with appropriate culture media. Originated organoid cultures were then submitted to a minimum of 5 passages followed by a freeze-thaw cycle before deemed established culture. To validate organoid tumour origin, we then performed whole-genome sequencing of paired organoid and respective fresh tumour. Results The established patient-derived organoids from colorectal liver metastasis add an overall mutation match of > 80% when compared to with the original tumour. We have found so far two CRLM organoid lines with mutations in the helical domain of PIK3CA (E545A and E542K). Conclusions We have demonstrated patient-derived organoids recapitulate the genome of their tumour of origin. Libraries of these primary cell models should in the near future be used to more accurately determine drug effectiveness prior to clinical trials. Ongoing testing of Alpelisib alone or in combination with other PI3K pathway target genes will determine whether these patients could benefit from these drugs. Legal entity responsible for the study Barros-Silva, J.D. Funding Cancer Research UK. Disclosure All authors have declared no conflicts of interest.

Aim NHS England deems 90-day readmission rates as a marker of quality of care. The causes of readmission have not been previously reported in the UK. The aim of this study was to examine the factors associated with 90-day readmission following colorectal cancer surgery at a hospital trust with a catchment population 1.2 million. Method A retrospective review was performed of all patients undergoing resection for colorectal cancer between January 2012 and December 2013. Unplanned readmission was defined as an emergency admission to the trust for any cause within 90 days of surgery. Readmission analyses were restricted to patients discharged from hospital within 28 days of resection. Results A total of 570 patients underwent surgery, of whom 522 were discharged within 28 days and are included for readmission analysis. The readmission rate was 24.3% (127 patients with a total of 163 episodes of hospital readmissions) within 90 days following surgery. The most frequent cause for readmission was complications related to adjuvant chemotherapy (18.4%) followed by wound-related complications (14.1%). Most patients presenting with wound-related complications were admitted within 60 days and patients with chemotherapy-related complications after 61 days; 13/127 (10.2%) patients who were readmitted underwent emergency surgery, and one patient died following readmission. Multivariate analysis demonstrated that comorbidity was the only independent risk factor. Conclusion Ninety-day readmissions include a high number of readmissions secondary to chemotherapy-related complications, whereas most surgical-related readmission present within 60 days.