O Ng

Iron therapy for pre-operative anaemia

BACKGROUNDnPre-operative anaemia is common and occurs in up to 76% of patients. It is associated with increased peri-operative allogeneic blood transfusions, longer hospital lengths of stay and increased morbidity and mortality. Iron deficiency is one of the most common causes of this anaemia. Oral iron therapy has traditionally been used to treat anaemia but newer, safer parenteral iron preparations have been shown to be more effective in other conditions such as inflammatory bowel disease, chronic heart failure and post-partum haemorrhage. A limited number of studies look at iron therapy for the treatment of pre-operative anaemia. The aim of this Cochrane review is to summarise the evidence for use of iron supplementation, both enteral and parenteral, for the management of pre-operative anaemia.nnnOBJECTIVESnThe objective of this review is to evaluate the effects of pre-operative iron therapy (enteral or parenteral) in reducing the need for allogeneic blood transfusions in anaemic patients undergoing surgery.nnnSEARCH METHODSnWe ran the search on 25 March 2015. We searched the Cochrane Injuries Groups 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, clinical trials registries, conference abstracts, and we screened reference lists.nnnSELECTION CRITERIAnWe included all randomised controlled trials (RCTs) which compared pre-operative iron monotherapy to placebo, no treatment, standard of care or another form of iron therapy for anaemic adults undergoing surgery. Anaemia was defined by haemoglobin values less than 13 g/dL for males and 12 g/dL for non-pregnant females.nnnDATA COLLECTION AND ANALYSISnData were collected by two authors on the proportion of patients who receive a blood transfusion, amount of blood transfused per patient (units) and haemoglobin measured as continuous variables at pre-determined time-points: pre-treatment, pre-operatively but post-treatment, and post-operatively. Statistical analysis was performed using the Cochrane statistical software, Review Manager 2014. Outcome data were summarised in tables and a forest plot.nnnMAIN RESULTSnThree prospective randomised controlled studies evaluated pre-operative iron therapy to correct anaemia (two in colorectal and one in gynaecological surgery) and included 114 patients in total. One compared oral iron versus standard care (Lidder 2007); one intravenous iron versus control (Edwards 2009); and one study compared oral versus intravenous iron (Kim 2009). Both colorectal trials reported the primary outcome (proportion of patients who received allogeneic blood transfusions) and meta-analysis showed a reduction in blood transfusions with the administration of iron therapy, but the reduction was not statistically significant (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.27 to 1.18). All studies reported haemoglobin change but data for the anaemic patients were only available for two studies (Edwards 2009 and Kim 2009). Edwards 2009 showed no difference in haemoglobin at the end of treatment pre-operatively. The intravenous versus oral iron study showed an increase in haemoglobin with intravenous iron at the end of treatment pre-operatively (MD 1.90 g/dL, 95% CI 1.16 to 2.64; participants = 56), but the results are at high risk of bias because participants with less than 80% compliance with therapy were excluded from the analysis and compliance was lower in the oral iron group due to the side-effects of treatment (Kim 2009).None of the studies reported quality of life, short- or long-term mortality or post-operative morbidity.nnnAUTHORS CONCLUSIONSnThe use of iron therapy for pre-operative anaemia does not show a statistically significant reduction in the proportion of patients who received an allogeneic blood transfusion compared to no iron therapy. However, the 38 patients in our analysis falls far short of the 819 patients our information size calculation recommended to detect a 30% reduction in blood transfusions. Intravenous iron may be more effective than oral iron at increasing haemoglobin. However, all these conclusions are drawn from only three small randomised controlled studies. Further well designed, adequately powered randomised controlled studies are required to determine the true effectiveness of iron therapy for pre-operative anaemia.

Iron, microbiota and colorectal cancer

SummaryIron 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 axa0shift 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.

Colorectal cancer outcomes in patients aged over 85 years

INTRODUCTIONnThe prevalence of colorectal cancer is increasing in the elderly. We examined the treatment and outcomes in our institution of patients aged over 85 years with proven colorectal adenocarcinoma.nnnMETHODSnOne hundred and five patients were identified and stratified by treatment received: curative surgery (CS), other treatments (OT) or best supportive care (BSC). Data on demographics, staging, treatment and survival was collected and analysed.nnnRESULTSnForty two patients received CS, 36 OT and 27 BSC. While the treated groups (CS and OT) were similar in terms of age (p=0.35) and staging (p=0.16), BSC patients were significantly older and had higher stage disease (p<0.01). Survival was significantly poorer among BSC patients, at a mean of 9.7 months (95% confidence interval [CI] 4.7-14.7) versus 41.6 months (95% CI 32.5-50.7) and OT 27.3 months (95% CI 20.4-34.1) for the CS and OT groups (p<0.001). There was no significant survival difference between CS and OT groups within 2 years of treatment (p=0.12). Thereafter, OT patients had a very similar 5-year survival to that of the BSC group, at 13% versus 43% in CS patients (p<0.001).nnnCONCLUSIONSnThese data suggest that, up to 2 years following treatment, the risks of resectional surgery for colorectal cancer may neutralise any benefit. However, those that survive beyond this period show improvements. The challenge of improving patient selection is most acute in the growing ageing population, and highlights the current focus on presenting all treatment options to a reasonable patient.

PWE-027 An interim analysis of the ‘getting fit’ project in nottingham: integrating faecal immunochemical testing in a two week wait pathway

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 <120u2009g/L women, <130u2009g/L men(WHO). 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<0.01). 24.9% of FIT samples yielded a zero result, 68.6% a faecal haemoglobin <10 µgHb/gFaeces and 91.1% a result <150 µgHb/gFaeces. Using a cut off of <10 µgHb/gFaeces the sensitivity for diagnosis of colorectal cancer was 85.7% (95%u2009CI 57.2%–98.2%) and specificity 71.1% (95% CI 65.7%–76.0%) with a cut off of <150 µgHb/gFaeces the sensitivity was 78.6% (95%CI 49.2%–95.3%) and specificity of 94% (95% CI 91.0%–96.5%). The PPV was 11.7% and 37.9%u2009respectively for <10 µgHb/gFaeces and <150 µgHb/gFaeces with a NPV of 99% for both. All cancers were diagnosed in patients who were either anaemic or had a FIT>150 µgHb/gFaeces. Conclusion We report a high return rate for FIT within a 2WW pathway and a turnaround time of <14 days in most cases. The most appropriate cut-off for FIT in symptomatic patients is yet to be determined but other factors such as anaemia should be considered when designing pathway. Disclosure of Interest None Declared

PTU-113 Hepcidin does not predict response to iron therapy in pre-operative anaemia in patients with colorectal cancer

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 >56u2009ng/ml. Results Both oral and intravenous iron groups were similar at baseline for recruitment haemoglobin (9.9u2009g/dL and 9.6u2009g/dL respectively, p=0.2). Median hepcidin levels were 1.9u2009ng/mL (range 0–86) in the oral iron group and 1.7u2009ng/mL (range 0–205u2009ng/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 (1.14u2009g/dL) compared to low hepcidin levels (1.12u2009g/dL) with no statistical difference found (p=0.949). Subset analysis of oral and intravenous groups also showed no differences (p=0.679u2009and p=0.775u2009respectively). Conclusion In this study, neither absolute hepcidin nor high hepcidin levels>56u2009ng/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

PWE-006 Differential immune responses between proximal and distal colorectal cancer

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=0.01u2009respectively). 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=0.01u2009respectively). 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

PTU-110 The use of pre-operative intravenous iron improves post-operative patient reported quality of life in anaemic colorectal cancer patients: results from a multicentre randomised controlled trial.

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<0.01), Vitality (Oral 60.49u [53.7-67.3]; IV 74.83u [69.2-80.5]; P<0.001). EQ5D scores for the visual analogue scale were also significantly higher in the IV group at outpatient review (OI 70.9u [65.1-76.8]; IV 82.53u [77.8-87.2]; P<0.001), with parity in the remaining 4 components. Furthermore, significant differences were evident in FACT-AN Total scores (Oral 148.3u [139-158];IV 166.1u [160-172.3]; P<0.01), FACT-AN Anaemia subscale scores (Oral 59.6u [54.4-64.8]; IV 69.1u [65.7-72.5]; P<0.01), Functional Well Being (Oral 20.2u [17.9-22.5]; IV 24.1u [22.2-26];P<0.01) and Emotional Well Being (Oral 19.9u [18.5-21.2]; IV 21.5u [20-23]; P<0.05) at outpatient review. None of the QOL measures had higher scores in the oral group. 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