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Background: Anaemia is highly prevalent in people with advanced, palliative cancer yet sufficiently effective and safe treatments are lacking. Oral iron is poorly tolerated, and blood transfusion offers only transient benefits. Intravenous iron has shown promise as an effective treatment for anaemia but its use for people with advanced, palliative cancer lacks evidence. Aims: To assess feasibility of the trial design according to screening, recruitment, and attrition rates. To evaluate the efficacy of intravenous iron to treat anaemia in people with solid tumours, receiving palliative care. Design: A multicentre, randomised, double blind, placebo-controlled trial of intravenous iron (ferric derisomaltose, Monofer®). Outcomes included trial feasibility, change in blood indices, and change in quality of life via three validated questionnaires (EQ5D5L, QLQC30, and the FACIT-F) over 8 weeks. (ISRCTN; 13370767). Setting/Participants: People with anaemia and advanced solid tumours who were fatigued with a performance status ⩽2 receiving support from a specialist palliative care service. Results: 34 participants were randomised over 16 months (17 iron, 17 placebo). Among those eligible 47% of people agreed to participate and total study attrition was 26%. Blinding was successful in all participants. There were no serious adverse reactions. Results indicated that intravenous iron may be efficacious at improving participant haemoglobin, iron stores and select fatigue specific quality of life measures compared to placebo. Conclusion: The trial was feasible according to recruitment and attrition rates. Intravenous iron increased haemoglobin and may improve fatigue specific quality of life measures compared to placebo. A definitive trial is required for confirmation.

Oral iron promotes intestinal tumourigenesis in animal models. In humans, expression of iron transport proteins are altered in colorectal cancer. This study examined whether the route of iron therapy alters iron transport and tumour growth. Colorectal adenocarcinoma patients with pre-operative iron deficiency anaemia received oral ferrous sulphate (n = 15), or intravenous ferric carboxymaltose (n = 15). Paired (normal and tumour tissues) samples were compared for expression of iron loading, iron transporters, proliferation, apoptosis and Wnt signalling using immunohistochemistry and RT-PCR. Iron loading was increased in tumour and distributed to the stroma in intravenous treatment and to the epithelium in oral treatment. Protein and mRNA expression of proliferation and iron transporters were increased in tumours compared to normal tissues but there were no significant differences between the treatment groups. However, intravenous iron treatment reduced ferritin mRNA levels in tumours and replenished body iron stores. Iron distribution to non-epithelial cells in intravenous iron suggests that iron is less bioavailable to tumour cells. Therefore, intravenous iron may be a better option in the treatment of colorectal cancer patients with iron deficiency anaemia due to its efficiency in replenishing iron levels while its effect on proliferation and iron metabolism is similar to that of oral iron treatment.

Aim Preoperative iron is frequently used for the correction of anaemia in colorectal cancer surgery. However, enteral iron intake may promote tumour growth and progression which could influence cancer recurrence and patient survival. We explore the long-term outcomes of patients receiving either oral or intravenous iron replacement therapy as part of a previous randomized controlled trial. Methods The IVICA trial randomized anaemic colorectal cancer patients to receive either oral (OI, control) or intravenous (IVI, treatment) iron prior to their elective operation. Follow-up analysis of all patients recruited to this multicentre trial who underwent surgical resection with curative intent was performed. Kaplan-Meier survival estimates and Cox proportional hazard models were used to compare groups. A pooled group multivariable analysis comparing patients who achieved resolution of anaemia preoperatively to those who did not was also undertaken. Results In all, 110 of the 116 patients previously enrolled were eligible for analysis (OI n = 56, IVI n = 54). Median overall follow-up duration was 61 months (interquartile range 46-67). No significant difference in 5-year overall survival (hazard ratio (HR) 1.22, 95% CI 0.65-2.28, P = 0.522) or disease-free survival (HR 1.08, 95% CI 0.61-1.92, P = 0.79) was observed between OI and IVI. A pooled analysis of treatment groups found that preoperative resolution of anaemia led to improved 5-year overall survival on multivariable analysis (HR 3.38, 95% CI 1.07-11.56, P = 0.044). Conclusion We recommend IVI for the preoperative correction of anaemia. Route of iron therapy did not significantly influence survival. Preoperative anaemia correction may lead to an overall survival advantage following elective colorectal cancer surgery.

Aims According to Good Surgical Practice set by the RCS England, surgeons need to keep themselves up to date and maintain the competence in all areas of their practice. Literature and guidelines recommended the use of AirSeal insufflation in laparoscopic surgery for the safety during the first surge of Covid-19. Our objectives were to measure the level of knowledge and confidence of surgical trainees in using the AirSeal insufflation system in laparoscopic surgery at our institution and to help trainees achieve competence. Method Multiple small group training sessions were delivered to 14 surgical doctors adhering to safety protocols. The concept of the AirSeal insufflation system, its benefits, limitations, set up and troubleshooting were delivered using lectures, videos and hands-on training. The change in level of knowledge and confidence in practical skills were assessed by analyzing the responses to the questionnaire completed before and after the course. Results Conclusion The dramatic improvement in self-perceived confidence of practical skills and knowledge of the AirSeal system was achieved among surgical doctors. Adaptation to the situation and introduction of this advanced technology to the trainees in elective and emergency settings helped promote the skills and safety at workplace during this pandemic especially with the support of flexible training sessions.

Aims Appendicitis, biliary disease and abscesses make up almost half of the emergency general surgery (EGS) workload. Our aim was to establish whether the shift towards non-operative management during the COVID-19 pandemic for these conditions has led to adverse patient outcomes. Methods Patient data were analysed from a prospective EGS database at a large UK tertiary centre. Patients were grouped by admission date into quarters (January-March, April-June, July-September, October-December) and compared with the corresponding time period from the preceding year. Results EGS saw 8226 and 7589 patients in 2019 and 2020 respectively. Following the first lockdown EGS admissions fell by 31%. Operative management of appendicitis fell from nearly 100% in 2019 to 32.9% and 54.7% in two of the four study periods. Complicated appendicitis was more common in 2020 leading to a 50% rise in length of stay (LOS), 4.5 days average. 30 day readmissions increased by 228% (n = 7, 2019 v n = 16, 2020). Biliary disease was managed conservatively with 11 patients undergoing percutaneous drainage from Apr-Dec 2020.Very few patients received emergency cholecystectomy in 2019 or 2020 due to institution preference. Readmission rates and LOS remained similar between years. Fewer abscesses were seen and operated on in 2020 with similar readmission rates and LOS between years. Conclusions Non-operative management and delays in presentation of appendicitis during the pandemic has had an adverse effect on patient outcomes. The rise in more complex cases has led to higher readmission rates and longer lengths of stay. The outcomes for biliary disease and abscesses remained unchanged.

Background New national guidance on urgent referral for investigation of colorectal cancer included faecal occult blood testing in 2015. A service evaluation of faecal immunochemical testing (FIT) and anaemia as risk stratification tools in symptomatic patients suspected of having CRC was undertaken. Methods Postal FIT was incorporated into the colorectal cancer 2-week wait (2WW) pathway for all patients without rectal bleeding in 2016. Patients were investigated in the 2WW pathway as normal, and outcomes of investigations were recorded prospectively. Anaemia was defined as a haemoglobin level below 120 g/l in women and 130 g/l in men. Results FIT kits were sent to 1106 patients, with an 80·9 per cent return rate; 810 patients completed investigations and 40 colorectal cancers were diagnosed (4·9 per cent). FIT results were significantly higher in patients with anaemia (median (i.q.r.) 4·8 (0·8-34·1) versus 1·2 (0-6·4) μg Hb/g faeces in those without anaemia; P

Background Intravenous iron is now the standard treatment to correct preoperative anaemia. However, iron may promote tumour growth and progression which could influence cancer recurrence and survival. We explore the long term postoperative outcomes of patients receiving oral (OI) or intravenous iron (IVI) as part of a randomised controlled trial. Method The multicentre IVICA trial randomised anaemic colorectal cancer patients in a 1:1 fashion to receive either OI or IVI prior to their elective operation. Follow up analysis of all patients was performed and Kaplan-Meier survival estimates and Cox proportional hazard models were used to compare groups. A pooled analysis comparing patients who did/did not achieve preoperative resolution of anaemia was also undertaken. Result, Data were available for 106 of the 116 IVICA patients (OI n=55, IVI n=51). Median follow up was 61 months (IQR 38-68, [range 1-80]). Overall survival estimates at 3 and 5 years were 82%(95% CI 76-90) and 72%(58-83) respectively for OI and 75%(61-86) and 59%(45-72) for IVI, P=0.106. No significant difference in 5-year overall survival (HR 1.73, 95% CI 0.90-3.34 P=0.102) or disease-free survival (HR 1.50, 95% CI 0.83-2.73 P=0.182) was observed between groups. Those non-anaemic at operation demonstrated improved 5 year overall survival (HR 3.26 [1.01-10.58], P=0.05). Non-significant trends in improved disease-free survival (HR 2.29 [0.91-5.81], p=0.08) were observed for the non-anaemic group Conclusion Preoperative correction of anaemia confers a postoperative survival advantage following elective colorectal cancer surgery. Due to its superior efficacy intravenous iron is recommended as the treatment of choice for this anaemia. Take-home message Preoperative correction of anaemia, achieved most effectively with intravenous iron, may offer improved long term postoperative survival after colorectal cancer surgery.

Background: Oral iron promotes intestinal tumourigenesis in animal models. In humans, expression of iron transport proteins are altered in colorectal cancer. This study examines whether the route of iron therapy alters iron transport and tumour growth. Methods: Colorectal adenocarcinoma patients with pre-operative iron deficiency anaemia received oral ferrous sulphate (n=15), or intravenous ferric carboxymaltose (n=15). Paired (normal and tumour tissues) samples were compared for expression of iron loading, iron transporters, proliferation, apoptosis, Wnt signalling pathway and microsatellite instability using immunohistochemistry and RT-PCR. Results: Iron loading was increased in tumour and distributed to the stroma in intravenous treatment and to the epithelium in oral treatment. The protein and mRNA expression of iron transporters were increased in tumours compared to normal tissues but there were no significant differences between the treatment groups. However, intravenous iron treatment reduced ferritin mRNA levels in tumours (pConclusion: Iron distribution to non-epithelial cells in intravenous iron treatment suggests that iron is less bioavailable to tumour cells. Therefore, intravenous iron supplementation could be a safer option in the treatment of colorectal cancer patients with iron deficiency anaemia due to the differential compartmentalisation of iron within the intestinal mucosa and its efficiency in replenishing body iron levels without increasing the risk of tumour growth.Trial registration: The study was registered with the Medicines and Healthcare Regulatory Agency, clinical trials.gov (NCT01927328) and EudraCT (2013-000209-22).

Received 15th October 2020. Accepted 15th October 2020.Published online 10th November 2020. Issue published 1st January 2021.

Background Preoperative anaemia is common and occurs in 5% to 76% of patients preoperatively. It is associated with an increased risk of perioperative allogeneic blood transfusion, longer hospital stay, and increased morbidity and mortality. Iron deficiency is one of the most common causes of anaemia. Oral and intravenous iron therapy can be used to treat anaemia. Parenteral iron preparations have been shown to be more effective in conditions such as inflammatory bowel disease, chronic heart failure and postpartum haemorrhage due to rapid correction of iron stores. A limited number of studies has investigated iron therapy for the treatment of preoperative anaemia. The aim of this Cochrane Review is to summarise the evidence for iron supplementation, both enteral and parenteral, for the management of preoperative anaemia. Objectives To evaluate the effects of preoperative iron therapy (enteral or parenteral) in reducing the need for allogeneic blood transfusions in anaemic patients undergoing surgery. Search methods We ran the search on 30 July 2018. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic and Embase (Ovid), CINAHL Plus (EBSCO), PubMed, and clinical trials registries, and we screened reference lists. We ran a top-up search on 28 November 2019; one study is now awaiting classification. Selection criteria We included all randomised controlled trials (RCTs) that compared preoperative iron monotherapy to placebo, no treatment, standard care or another form of iron therapy for anaemic adults undergoing surgery. We defined anaemia as haemoglobin values less than 13 g/dL for males and 12 g/dL for non-pregnant females. Data collection and analysis Two review authors collected data and a third review author checked all collected data. Data were collected on the proportion of patients who receive a blood transfusion, the amount of blood transfused per patient (units), quality of life, ferritin levels and haemoglobin levels, measured as continuous variables at the following predetermined time points: pretreatment (baseline), preoperatively but postintervention, and postoperatively. We performed statistical analysis using the Cochrane software, Review Manager 5. We summarised outcome data in tables and forest plots. We used the GRADE approach to describe the quality of the body of evidence. Main results Six RCTs, with a total of 372 participants, evaluated preoperative iron therapy to correct anaemia before planned surgery. Four studies compared iron therapy (either oral (one study) or intravenous (three studies)) with no treatment, placebo or usual care, and two studies compared intravenous iron therapy with oral iron therapy. Iron therapy was delivered over a range of periods that varied from 48 hours to three weeks prior to surgery. The 372 participants in our analysis fall far short of the 819 required - as calculated by our information size calculation - to detect a 30% reduction in blood transfusions. Five trials, involving 310 people, reported the proportion of participants who received allogeneic blood transfusions. Meta-analysis of iron therapy versus placebo or standard care showed no difference in the proportion of participants who received a blood transfusion (risk ratio (RR) 1.21, 95% confidence interval (CI) 0.87 to 1.70; 4 studies, 200 participants; moderate-quality evidence). Only one study that compared oral versus intravenous iron therapy measured this outcome, and reported no difference in risk of transfusion between groups. There was no difference between the iron therapy and placebo/standard care groups for haemoglobin level preoperatively at the end of the intervention (mean difference (MD) 0.63 g/dL, 95% CI -0.07 to 1.34; 2 studies, 83 participants; low-quality evidence). However, intravenous iron therapy produced an increase in preoperative postintervention haemoglobin levels compared with oral iron (MD 1.23 g/dL, 95% CI 0.80 to 1.65; 2 studies, 172 participants; low-quality evidence). Ferritin levels were increased by intravenous iron, both when compared to standard care ((MD 149.00, 95% CI 25.84 to 272.16; 1 study, 63 participants; low-quality evidence) or to oral iron (MD 395.03 ng/mL, 95% CI 227.72 to 562.35; 2 studies, 151 participants; low-quality evidence). Not all studies measured quality of life, short-term mortality or postoperative morbidity. Some measured the outcomes, but did not report the data, and the studies which did report the data were underpowered. Therefore, uncertainty remains regarding these outcomes. The inclusion of new research in the future is very likely to change these results. Authors' conclusions The use of iron therapy for preoperative anaemia does not show a clinically significant reduction in the proportion of trial participants who received an allogeneic blood transfusion compared to no iron therapy. Results for intravenous iron are consistent with a greater increase in haemoglobin and ferritin when compared to oral iron, but do not provide reliable evidence. These conclusions are drawn from six studies, three of which included very small numbers of participants. Further, well-designed, adequately powered, RCTs are required to determine the true effectiveness of iron therapy for preoperative anaemia. Two studies are currently in progress, and will include 1500 randomised participants.

Summary Background Closure of an abdominal stoma, a common elective operation, is associated with frequent complications; one of the commonest and impactful is incisional hernia formation. We aimed to investigate whether biological mesh (collagen tissue matrix) can safely reduce the incidence of incisional hernias at the stoma closure site. Methods In this randomised controlled trial (ROCSS) done in 37 hospitals across three European countries (35 UK, one Denmark, one Netherlands), patients aged 18 years or older undergoing elective ileostomy or colostomy closure were randomly assigned using a computer-based algorithm in a 1:1 ratio to either biological mesh reinforcement or closure with sutures alone (control). Training in the novel technique was standardised across hospitals. Patients and outcome assessors were masked to treatment allocation. The primary outcome measure was occurrence of clinically detectable hernia 2 years after randomisation (intention to treat). A sample size of 790 patients was required to identify a 40% reduction (25% to 15%), with 90% power (15% drop-out rate). This study is registered with ClinicalTrials.gov, NCT02238964. Findings Between Nov 28, 2012, and Nov 11, 2015, of 1286 screened patients, 790 were randomly assigned. 394 (50%) patients were randomly assigned to mesh closure and 396 (50%) to standard closure. In the mesh group, 373 (95%) of 394 patients successfully received mesh and in the control group, three patients received mesh. The clinically detectable hernia rate, the primary outcome, at 2 years was 12% (39 of 323) in the mesh group and 20% (64 of 327) in the control group (adjusted relative risk [RR] 0·62, 95% CI 0·43–0·90; p=0·012). In 455 patients for whom 1 year postoperative CT scans were available, there was a lower radiologically defined hernia rate in mesh versus control groups (20 [9%] of 229 vs 47 [21%] of 226, adjusted RR 0·42, 95% CI 0·26–0·69; p

Introduction Colorectal cancer (CRC), a major cause of cancer-related mortality, is associated with iron deficiency anaemia (IDA) and is typically treated with oral iron. Iron is an essential nutrient element that is required for a diverse range of biological activities including the immune function (1). However, studies in animal and cell line models have shown that accumulation of iron in the gut can generate toxic reactive oxygen species and proinflammatory cytokines that results in tissue damage and CRC progression (2). We studied, for the first time in humans, the effect of oral (OI) versus intravenous iron (IVI) treatment on iron distribution, immune cell infiltration and systemic cytokine profile in CRC patients with IDA. Methods Patients with CRC and IDA received oral-ferrous sulphate (n=20) or intravenous ferric carboxymaltose (n=20) for 2 weeks. Tissue was analysed for iron loading using Prussian-Blue staining. Tissue cytokine and immune cell distribution was determined using immunohistochemistry. Systemic cytokine production was evaluated by multiplex-cytokine assays. Results Iron expression was distributed to the epithelium of tumour tissues in OI treatment (p Conclusions Intravenous iron is compartmentalised to non-epithelial cells indicating that iron is potentially less bio-available to the tumour cells. Oral iron treatment induces inflammatory immune responses both systemically and within the tumour microenvironment. Further functional studies are ongoing to evaluate the mucosal immune response to differential iron loading. References Bergman M, et al., Biomed Pharmacother. 2005;59(6):307. Glei M, et al., Mutat Res. 2002 26;519(–):151.

Anaemia is associated with a reduction in quality of life, and is common in patients with colorectal cancer . We recently reported the findings of the intravenous iron in colorectal cancer-associated anaemia (IVICA) trial comparing haemoglobin levels and transfusion requirements following intravenous or oral iron replacement in anaemic colorectal cancer patients undergoing elective surgery. In this follow-up study, we compared the efficacy of intravenous and oral iron at improving quality of life in this patient group. We conducted a multicentre, open-label randomised controlled trial. Anaemic colorectal cancer patients were randomly allocated at least two weeks pre-operatively, to receive either oral (ferrous sulphate) or intravenous (ferric carboxymaltose) iron. We assessed haemoglobin and quality of life scores at recruitment, immediately before surgery and at outpatient review approximately three months postoperatively, using the Short Form 36, EuroQoL 5-dimension 5-level and Functional Assessment of Cancer Therapy - Anaemia questionnaires. We recruited 116 anaemic patients across seven UK centres (oral iron n = 61 (53%), and intravenous iron n = 55 (47%)). Eleven quality of life components increased by a clinically significant margin in the intravenous iron group between recruitment and surgery compared with one component for oral iron. Median (IQR [range]) visual analogue scores were significantly higher with intravenous iron at a three month outpatient review (oral iron 70, (60-85 [20-95]); intravenous iron 90 (80-90 [50-100]), p = 0.001). The Functional Assessment of Cancer Therapy - Anaemia score comprises of subscales related to cancer, fatigue and non-fatigue items relevant to anaemia. Median outpatient scores were higher, and hence favourable, for intravenous iron on the Functional Assessment of Cancer Therapy - Anaemia subscale (oral iron 66 (55-72 [23-80]); intravenous iron 71 (66-77 [46-80]); p = 0.002), Functional Assessment of Cancer Therapy - Anaemia trial outcome index (oral iron 108 (90-123 [35-135]); intravenous iron 121 (113-124 [81-135]); p = 0.003) and Functional Assessment of Cancer Therapy - Anaemia total score (oral iron 151 (132-170 [69-183]); intravenous iron 168 (160-174 [125-186]); p = 0.005). These findings indicate that intravenous iron is more efficacious at improving quality of life scores than oral iron in anaemic colorectal cancer patients.

Anaemia reduces the efficacy of chemotherapy in gastric cancer. However, it has not been studied in oesophageal cancer. We investigated whether anaemia impacts on survival and the efficacy of chemotherapy, in adenocarcinoma of the oesophagus for those undergoing neoadjuvant chemotherapy and then surgical resection.This prospective study included 268 patients who received neoadjuvant chemotherapy for oesophageal adenocarcinoma. Patient clinical data as well as Mandard's tumor regression grading (TRG), haemoglobin pre-chemotherapy and during the chemotherapy were compiled. The association between anaemia and TRG was tested using Chi-squared analysis, whilst survival outcomes were investigated by Kaplan-Meier and Cox regression.One hundred participants were anaemic before chemotherapy whilst 224 were anaemic during chemotherapy cycles. Survival analyses found a significant association between lower haemoglobin levels and decreased overall survival (P=0.048). Comparing those without anaemia against those with moderate -severe anaemia (10.9 g/dL) found a statistically significant association in overall survival (P=0.026). Multivariate cox regression showed those with anaemia were statistically more likely to have decreased overall survival (HR 1.735, 95% CI, 1.050-2.867, P=0.032). No statistical association was seen between those with pre-chemotherapy anaemia and TRG (OR 0.675, 95% CI, 0.420-1.161, P=0.130) or those with anytime anaemia (OR 0.881, 95% CI, 0.406-1.914, P=0.931).These results suggest that anaemia is associated with poorer overall survival time, with lower haemoglobin levels reducing prognosis. However, there does not appear to be an association between anaemia and chemotherapy response in oesophageal adenocarcinoma.

Anemia is common with esophagogastric adenocarcinoma, increasing mortality, blood transfusions, and reducing quality of life (QOL). No clear evidence exists for safe and effective treatment.Anemic patients (Hb12 g/dl women,13 g/dl men) with esophagogastric adenocarcinoma were recruited before initiation of palliative chemotherapy. Patients were randomized to standard care or single dose of intravenous iron isomaltoside (IVI) before chemotherapy. Post-chemotherapy changes in hemoglobin (Hb), ferritin, transferrin saturations (TSAT), blood transfusions, and QOL were recorded for three cycles of chemotherapy.Twenty-seven patients were randomized to standard care (n = 13) or IVI (n = 14). No significant change in Hb was seen (standard care MD -0.6 g/dl 95% CI -0.1-1.1 g/dl, P = 0.336; IVI MD +0.5 g/dl 95% CI -0.1-1.1 g/dl, P = 0.903). An increase in ferritin was seen with IVI after cycle one of chemotherapy (standard care 116 ng/ml; IVI 770 ng/ml, P 0.05). No difference in blood transfusions was seen between groups (P = 0.851). IVI improved QOL with physical well-being, emotional well-being, anemia-specific QOL, trial outcome index, and total scores all exceeding minimum clinically important difference. No improvement was seen with standard care.This feasibility study suggests IVI improves quality of life and ferritin. Larger adequately powered studies are required to definitively conclude if hemoglobin and blood transfusion changes with IVI.

Introduction Anaemia is associated with cancer. In 2014 a new form was introduced in our department requesting a haemoglobin (Hb) result on every two-week wait referral for suspected colorectal cancer (CRC). The aim of this study was to review the impact of this intervention. In particular, the significance of any evidence of anaemia (without additional indices) was investigated. Methods A review was conducted of 1,500 consecutive suspected CRC referrals recorded prospectively over a 10-month period. Data on demographics, referral Hb, referral criteria and outcomes were analysed. Anaemia was defined according to World Health Organization criteria (Hb Results Overall, 1,015 patients were eligible for inclusion in the study. Over a third (38.2%) were documented as anaemic on referral. These patients were three times more likely to be diagnosed with CRC than non-anaemic patients (odds ratio [OR]: 3.22, 95% confidence interval [CI]: 1.87–5.57). Using a more stringent threshold (Hb Conclusions Nearly a quarter of patients not referred with iron deficiency anaemia had evidence of anaemia and this was still associated with a higher rate of CRC detection. A full blood count alone might help to risk stratify symptoms such as change in bowel habit in patients on urgent pathways and identify those cases most likely to benefit from invasive investigation.

Introduction Colorectal cancer (CRC) is a major cause of mortality. Dendritic cells (DC) promote tumour immunity or tolerance dictated by tissue microenvironment. Proximal colon (right-sided) CRC has lower incidence but poorer prognosis than distal colon (left-sided) CRC. This may be due to immunological differences between the proximal and distal colon. However, cellular and molecular studies on these differences especially in CRC are scarce. We aimed to characterise the immune activity in both compartments. Method Activation and migration of DC from human mucosal and tumour biopsies in health and CRC were investigated using flow-cytometry, immunohistology. Functional studies were performed using migration assay techniques. E-Cadherin, a tumour dissemination inhibitor was determined by real time PCR in a separate group of tumours from anaemic CRC patient. Results Co-stimulatory molecules (CD40/CD86) were expressed on more DC from proximal than distal colon in health and CRC (p=0.03; p=0.01 respectively). In CRC, DC from proximal mucosa and tumour showed increased skin-homing (CLA) and ILT3 (marker for immature DC) indicating reduced potential to focus immune activity to this compartment (p=0.03; p=0.01 respectively). CRC-DC showed increased CCR7 (lymph node homing) with greater migration but with negative correlation with tumour size. E-Cadherin mRNA fold-change was significantly lower on proximal tumour cells compared with those in the distal compartment. Functional studies using supernatants from normal mucosae or tumours reproduced the above changes in CRC-DC; changes thus reflected changed gut micro-environment in CRC. Conclusion Higher immune activity, in proximal colon, may underlie lower tumour incidence but higher tumour aggression due to tumour evolution in immunologically active microenvironment. This may have an impact on colorectal cancer treatment, for example, optimisation of current therapies based on the anatomical site of the colorectal tumour. Hence, establishment of standardised management for colon cancer by tumour location is needed. Reference . Bernardo D, et al., Chemokine (C-C Motif) Receptor2 Mediates Dendritic Cell Recruitment to the Human Colon but Is Not Responsible for Differences Observed in Dendritic Cell Subsets, Phenotype, and Function Between the Proximal and Distal Colon. Cell Mol Gastroenterol Hepatol2016;2(1):22–39. Disclosure of Interest None Declared

Introduction Latest NICE guidance (NG12) on criteria warranting urgent referral for investigation for colorectal cancer (CRC) includes the use of faecal occult blood testing. We present an interim analysis of the ‘Getting FIT’ project – a service evaluation of faecal immunochemical testing (FIT) in symptomatic patients suspected of having CRC. Method In September 2016 we incorporated FIT into our Straight to test (STT) pathway with the support of our local commissioners. GPs were given access to FIT for eligible low risk patients using a specific referral form vetted by the STT team. In two week wait (2WW) referrals, excluding those for rectal bleeding, a FIT kit is posted to patients. STT patients received a vetting telephone call and were told they shall receive a FIT test. Patients are investigated as normal and FIT results, when available, used for prioritisation within our 2WW pathway. Anaemia was defined as haemoglobin We present the results of kits analysed on the OC Sensor according to manufacturer’s protocols (EIKEN OC-Sensor io) expressed in µgHb/gFaeces. Patient outcomes are prospectively recorded on our STT database. Data on patients who returned kits between 6/9/16 and 10/2/17 are included. Results 17 of 19 (89.5%) GP requests and 348 of 441 (78.9%) 2WW kits were returned. Median time for kit return was 7 days (Range 2–24 days) with 94.9% of returned kits received within 14 days. 343 kits yielded results that were analysable and of 325 patients undergoing investigation 14 had confirmed CRC (4.3%). FIT results were significantly higher in patients who were anaemic compared to non-anaemic patients (MannWhitney p 24.9% of FIT samples yielded a zero result, 68.6% a faecal haemoglobin 150 µgHb/gFaeces. Conclusion We report a high return rate for FIT within a 2WW pathway and a turnaround time of Disclosure of Interest None Declared

Introduction Anaemia is associated with multiple symptoms including fatigue which in turn can contribute to impaired quality of life. It is a common finding in colorectal cancer as a result of chronic insidious haemorrhage and impaired iron haemostasis. Consequently, colorectal cancer patients are at risk of the symptomatology of anaemia. Method Preoperative colorectal cancer patients (n=116) who were found to be anaemic (>1g/dL below the World Health Organisation definition) were randomised to receive either intravenous (IV) or oral iron. Quality of life (QOL) questionnaires were performed at; [i] recruitment, [ii] at least 14 days after iron therapy and [iii] post-operatively in the first outpatient follow-up. QOL assessments undertaken included the following; [a] Functional Assessment of Cancer Therapy-Anaemia (FACT-AN) [b] EuroQol EQ-5D-5L (EQ5D) and [c] modified Short-Form 36 (SF36) v1 questionnaires. Results Both groups were comparable in patient demographics, starting haemoglobin, operative details, tumour histology and time from recruitment to postoperative review (oral 101 days [IQR 62-193]; IV 91 days [IQR 61-135, P=0.98]. Despite homogeneity in all initial QOL scores at recruitment significant differences were evident between groups at outpatient review in the all bar two of the SF36 components including: General Health (Oral 64.79u [58.8-70.8]; IV 73.63u [68.4-78.8]; P Conclusion Intravenous iron is more efficacious than oral iron at improving the post-operative quality of life of anaemic colorectal cancer patients. The usage of intravenous iron should be considered in patients who are found to have colorectal cancer during evaluation of anaemia by Gastroenterologists to optimise these outcomes. Disclosure of Interest: M. Brookes Conflict with: Vifor International, Conflict with: Vifor International, B Keeler: None Declared, O Ng: None Declared, H Padmanabhan: None Declared, A Simpson: None Declared, A Acheson Conflict with: Vifor International

Introduction Iron is essential for the proliferation of all mammalian cells. We previously showed that the expression of iron transport proteins are altered in colorectal cancer (CRC) [1]. This is the first study to examine whether iron therapy further alters iron transport expression at both protein and mRNA level in human CRC. Method 30 patients with colorectal adenocarcinoma and pre-operative iron deficiency anaemia received iron therapy a minimum of 2 weeks before surgery as part of the IVICA trial (15 oral ferrous sulphate, 15 intravenous (IV) ferric carboxymaltose) [2]. Paired normal and tumour tissue from surgical resection were analysed for iron loading using Prussian blue staining; TfR1, DMT1 and ferroportin proteins using immunohistochemistry and IREB2, FTH1, TFRC and DMT1 mRNA using real time PCR. Expression was compared between normal and tumour and treatment groups. Results Iron loading was increased in tumour tissues compared to normal tissues (p 0.001). No significant differences in the other iron transporters were seen between treatment groups. Conclusion Similar to our previous findings iron loading is seen in CRC through an increase in the expression of iron transporters compared to normal colon. When the two treatment arms were compared the only significant difference seen was that tumour ferritin expression was higher in those receiving oral iron. This might suggest that iron supplementation by IV compared to oral iron lead to a differential effect on intracellular iron loading. Further work is needed to determine if IV iron supplementation is safer due to differential compartmentalisation of the iron within the mucosa which might avoid tumour cell iron loading. References . Brookes, MJ, et al. Modulation of iron transport proteins in human colorectal carcinogenesis . Gut2006;55(10):1449–60. . Keeler, BD, et al. Randomised clinical trial of preoperative oral versus intravenous iron in anaemic patients with colorectal cancer Br J Surg, 2017;104(3):214–221. Disclosure of Interest None Declared

Introduction Hepcidin has a key role in systemic iron homeostasis. We assessed if serum hepcidin predicts response to either intravenous or oral iron therapy in the treatment of pre-operative anaemia. Method As part of the IVICA trial [1], patients with iron-deficiency anaemia undergoing elective surgery for colorectal cancer were randomised to receive oral ferrous sulphate (n=58) or intravenous Ferinject (n=54) for a minimum of two weeks before surgery. Blood samples were taken at recruitment (prior to iron therapy) and on the day of surgery (after iron therapy). Clinical data was collected prospectively. Changes in haemoglobin from recruitment to day of surgery were measured. Serum were analysed using an ELISA assay to determine hepcidin levels. Association between hepcidin levels and mean haemoglobin change from recruitment to day of surgery were tested using the Mann Whitney U test. High hepcidin was defined as >56 ng/ml. Results Both oral and intravenous iron groups were similar at baseline for recruitment haemoglobin (9.9 g/dL and 9.6 g/dL respectively, p=0.2). Median hepcidin levels were 1.9 ng/mL (range 0–86) in the oral iron group and 1.7 ng/mL (range 0–205 ng/mL) in the IV iron group. No correlation was found between hepcidin levels and haemoglobin change in either oral or intravenous groups. Mean haemoglobin change was similar for those with high hepcidin levels (1.14 g/dL) compared to low hepcidin levels (1.12 g/dL) with no statistical difference found (p=0.949). Subset analysis of oral and intravenous groups also showed no differences (p=0.679 and p=0.775 respectively). Conclusion In this study, neither absolute hepcidin nor high hepcidin levels>56 ng/ml predicted response to iron therapy, irrespective of the route of administration of iron therapy. Reference . Keeler BD, et al. Randomised clinical trial of preoperative oral versus intravenous iron in anaemic patients with colorectal cancer. Br J Surg, 2017;104(3):214–221. Disclosure of Interest None Declared

Introduction Oral iron (but not intravenous iron) promotes intestinal tumourigenesis in animal models [1]. This is the first study to examine the effect of iron therapy on proliferation and apoptosis in human colorectal cancer (CRC) in vivo. Method 30 patients from the IVICA trial with CRC and pre-operative iron deficiency anaemia were given a minimum of 2 weeks iron therapy (15 oral ferrous sulphate, 15 intravenous ferric carboxymaltose) [2]. Tumour tissue and adjacent normal tissue from surgical resection were collected. Protein markers for proliferation (Ki67, betaccatenin) and apoptosis or DNA damage (p53, γH2AX) were analysed using immunohistochemistry. c-MYC mRNA was examined using real time PCR. Expression was compared with paired normal tissue and differences between treatment groups analysed. Results All markers of apoptosis, proliferation and DNA damage were more strongly expressed in tumour tissue compared to normal. Differences between treatment groups were seen in these proteins by immunohistochemistry but did not reach statistical significance. The intravenous group had similar Ki67 (35% oral vs 37% IV, p=0.77) and similar nuclear (16% oral vs 13% IV, p=0.6614) and membranous betaccatenin (67% oral vs 66% IV, p=0.89). Lower p53 (45% oral vs 24% IV, p=0.09) but similar γH2AX (32% oral vs 31% IV, p=0.91) were seen in the intravenous group. c-MYC mRNA fold-change were significantly higher in tumour cells compared with normal tissue (p Conclusion IV iron therapy does not cause significant increases in proliferation or apoptosis in tumours when compared to oral iron. This was despite IV iron being more effective in correcting clinical anaemia in the IVICA trial [2]. A trend towards increased proliferation and more apoptosis with oral iron therapy when compared to intravenous iron therapy is seen with c-MYC and p53. Our future studies will include a larger sample number and will also focus on the effect of intravenous therapy on systemic changes of proliferation and apoptosis markers in human colorectal cancer. References . Seril DN, et al. Systemic iron supplementation replenishes iron stores without enhancing colon carcinogenesis in murine models of ulcerative colitis: comparison with iron-enriched diet. Dig Dis Sci2005;50(4):696–707. . Keeler BD, et al. Randomised clinical trial of preoperative oral versus intravenous iron in anaemic patients with colorectal cancer. Br J Surg2017;104(3):214–221. Disclosure of Interest None Declared

Iron deficiency and anaemia are common in colorectal cancer. Replacement with oral or intravenous iron effectively treats this deficiency. However, mechanistic and population studies suggest that excess iron promotes colorectal carcinogenesis. Growing research into gut microbiota and dysbiosis suggests one explanation for this association. Iron is growth limiting for many pathogenic bacteria and may promote a shift in the ratio of pathogenic to protective bacteria. This may increase the toxic bacterial metabolites, promoting inflammation and carcinogenesis. This has important implications as we seek to correct anaemia in our patients.

Introduction Anaemia is common and new NICE guidelines (NG12) for suspected colorectal cancer (CRC) broaden the age and type of anaemia qualifying for urgent two week wait (2 WW) referral. Further, NICE now recommend iron therapy (including intravenous iron) for anaemia prior to surgery. Our study examines how anaemia in 2 WW referrals is related to outcome and the potential for iron therapy as treatment. Methods Retrospective review of 1000 consecutive patients from 01/12/2014 to 13/07/2015 referred for suspected CRC. Anaemia was defined by WHO ( Results 202/1000 (20.2%) had no haemoglobin at time of referral. 305/798 (38.2%) of patients were anaemic at the time of referral. Only 101/305 (33.1%) had been referred for anaemia and 204/305 (66.8%) for other symptoms. 173/305 (56.7%) had a ferritin recorded. Of 249 anaemic patients who completed investigations 40 (16.1%) had CRC detected. Anaemia was associated with detection of cancer (p Conclusion Anaemia (but not iron deficiency) is associated with CRC detection. About half of patients have no recorded ferritin on referral despite anaemia, but identification of iron deficiency is important as it indicates those patients that would likely benefit from iron therapy in anaemia. Nottingham Colorectal Service historically has not insisted on checking for iron deficiency in our 2 WW referral pathway, these results vindicates this approach and are consistent with new NICE guidance. The introduction of faecal occult blood testing in anaemia as per NICE guidance may help to identify those most likely to benefit from investigations. Disclosure of Interest None Declared

Introduction In the UK population those aged over 85 will almost double by 2037. An ageing population, rising bowel cancer and recognition that chronological age is no longer a barrier to individualised treatment, renders colorectal cancer (CRC) in this age-group increasingly important. We report the outcomes for patients over 85 diagnosed with CRC in our institution. The aim was to appraise treatment choices and outcomes in order to inform decision making for patients in this age group. Method We reviewed all patients from 2008–10 discussed in colorectal MDT >85 years old with proven colorectal adenocarcinoma. Data was collected from electronic notes, GP and public records. Patients were assigned to 3 treatment arms; curative surgery (CS), other treatments (OT) and best supportive care (BSC). OT group included chemotherapy, radiotherapy, local or endoscopic excision and stents. Results 105 patients (64 female) were included in this study. 42 had CS (7 laparoscopic), 36 OT and 27 BSC. Treated groups (CS and OT) were similar in age (p = 0.35) and staging (p = 0.16) while the BSC group were significantly older with higher stage disease (p Survival was significantly poorer in BSC than those who are treated, mean 9.7 months (95% CI 4.7–14.7) vs. 41.6 months (95% CI 32.5–50.7) for CS and 27.3 months (95% CI 20.4–34.1) for OT (p Right sided tumours dominated CS (p Conclusion Our study highlights that despite what is regarded curative treatment for CRC there appears to be no difference in survival over the first 2 years compared to other treatments. However, beyond 2 years a clear survival benefit is apparent. This is important when treating patients at the extremes of age who are the most likely to ask ‘what happens if I don’t have a big operation?’ and indeed, it is a duty of informed consent to talk about alternatives. Our results also suggest that the site of the cancer may matter. Right-sided cancers were more likely to be treated with CS. Rectal tumours were more likely to receive other treatment. Does this reflect our intuitive understanding of outcomes and risks in over 85 years old or are we prejudice? Disclosure of interest None Declared.

Introduction Anaemia is common in oesophagogastric cancer. Major operations performed for these cancers are associated with significant blood loss and need for transfusions. Concerns exist about the side effects of blood transfusion, cost and availability of donated blood. Our study aims to identify incidence of anaemia, change in haemoglobin, rates of blood transfusion and mortality associated with the diagnosis and treatment of oesophagogastric cancer. Method We conducted a retrospective analysis of all patients diagnosed with oesophagogastric cancer in 2012–2013 at a single high-volume referral centre. Data was collected on site, histology, staging, haemoglobin, blood transfusions, survival and treatment. WHO definitions were used to define anaemia. Results 550 patients were included in the study. Median haemoglobin at time of diagnosis was 127 g/L (37–188 g/L). 227 patients (45%) were anaemic at diagnosis. Higher haemoglobin at diagnosis improved survival (irrespective of a diagnosis of anaemia) with high normal haemoglobin (>150 g/L) showing significantly better survival than low normal haemoglobin (130–150 g/L), p Anaemia prior to surgery was also associated with poorer survival (p Conclusion Anaemia is common in oesophagogastric cancer and becomes worse during treatment. Neoadjuvant treatment increases the rates and severity of anaemia. Lower haemoglobin at diagnosis and anaemia prior to surgery are both associated with poorer survival and more blood transfusions. A more proactive strategy to the management of anaemia is required if we are to attempt to avoid the excess mortality and blood transfusions seen here in oesophagogastric cancer. Disclosure of interest None Declared.

Introduction Perioperative allogeneic red blood transfusions (ARBT) are associated with impaired short and long term outcomes. 1 Consequently, perioperative ARBT should be avoided, yet preoperative anaemia increases this need. The study aimed to compare the efficacy of preoperative intravenous (IVI) and oral iron (OI) in reducing ARBT use in anaemic patients undergoing colorectal cancer (CRC) surgery. Method 116 anaemic patients with non-metastatic CRC adenocarcinoma were recruited preoperatively and randomised to receive either OI (ferrous sulphate) or IVI (ferric carboxymaltose). Perioperative changes in Haemoglobin (HB) and ARBT were recorded across groups. Parametric data was compared with 2 tailed T-test and non-parametric data with Wilcoxon Rank test, and Mann-Whitney U test. Nominal data was compared with 2 tailed Chi squared test. Results There was no difference in demographic data between groups. HB levels at recruitment were comparable (OI 10.4g/dL 95% CI 10.1–10.7; IVI 10.2g/dL 95% CI 9.8–10.5; P = 0 .24), as was median treatment duration (OI 21days IQR15–33; IVI 21days IQR15–34; P = 0 .75). However, HB was higher on day of Surgery with IVI (11.9g/dL 95% CI 11.5–12.3 vs OI 11g/dL 95% CI 10.6–11.4; P .01). Median preoperative HB change in patients not transfused preoperatively was higher with IVI (1.5g/dL IQR0.9–2.6 vs. OI 0.5g/dL IQR-0.1–1.3; P .01). There were fewer anaemic patients at surgery in the IVI group after treatment (75% vs. 90% ; P .05). OI patients received a mean 0.63u (95% CI 0.26–1) from recruitment to day 28 postoperatively vs. mean 0.47u (95% CI 0.1–0.84) for IVI. Neither number of patients transfused ( P = 0 .33) nor mean units transfused ( P = 0 .54) differed over this period. When patients with heavy intraoperative losses (>1.5L) were excluded, a significant difference in mean units of blood transfused was seen up to 7 days post operatively ( n = 1 08; OI 0.6u 95% CI 0.23–0.96; IVI 0.16u 95% CI 0.01–0.3 ; P .05) and significantly less IVI patients were transfused (10% vs. 25%; P .05). Conclusion In patients undergoing CRC surgery, IVI appears more efficacious than OI at treating preoperative anaemia. It does not appear to minimise overall ARBT requirement, but may reduce ARBT use in the immediate perioperative period when the implications of ARBT are probably at their greatest. 2 Disclosure of interest B. Keeler: None Declared, J. Simpson: None Declared, O. Ng: None Declared, H. Padmanabhan: None Declared, M. Brookes Grant/ Research Support from: MB’s research department has received grant support from Syner-Med, UK, and Vifor Pharma, Switzerland, Speaker Bureau of: He has received honoraria or travel support for consulting or lecturing from the following companies: Vifor Pharma Ltd, Glattbrugg, Switzerland; Merck Sharp and Dohme Limited, UK. MB is also an advisory board member to Vifor International and to Sanofi UK, A. Acheson Grant/ Research Support from: AA’s research department has received grant support from Syner-Med, UK, Vifor Pharma, Switzerland, and Pharmacosmos A/S, Denmark, Consultant for: He is an advisory board member for Pharmacosmos A/S, Denmark., Conflict with: received honoraria or travel support for consulting or lecturing from the following companies: Ethicon Endosurgery, Johnson and Johnson Ltd, UK; Olympus, Essex, UK; and Vifor Pharma Ltd, Glattbrugg, Switzerland. References Acheson AG; Brookes MJ; Spahn DR. Effects of allogeneic red blood cell transfusions on clinical outcomes in patients undergoing colorectal cancer surgery:a systematic review and meta-analysis. Ann Surg. 2012;256(2):235–44 Nielsen HJ. Detrimental effects of perioperative blood transfusion. BJS 1995;82(5):582–7