The impact of pre-operative intravenous iron on quality of life after colorectal cancer surgery: outcomes from the intravenous iron in colorectal cancer-associated anaemia (IVICA) trial.

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.

Randomized clinical trial of preoperative oral versus intravenous iron in anaemic patients with colorectal cancer.

BACKGROUND: Treatment of preoperative anaemia is recommended as part of patient blood management, aiming to minimize perioperative allogeneic red blood cell transfusion. No clear evidence exists outlining which treatment modality should be used in patients with colorectal cancer. The study aimed to compare the efficacy of preoperative intravenous and oral iron in reducing blood transfusion use in anaemic patients undergoing elective colorectal cancer surgery. METHODS: Anaemic patients with non-metastatic colorectal adenocarcinoma were recruited at least 2 weeks before surgery and randomized to receive oral (ferrous sulphate) or intravenous (ferric carboxymaltose) iron. Perioperative changes in haemoglobin, ferritin, transferrin saturation and blood transfusion use were recorded until postoperative outpatient review. RESULTS: Some 116 patients were included in the study. There was no difference in blood transfusion use from recruitment to trial completion in terms of either volume of blood administered (P = 0·841) or number of patients transfused (P = 0·470). Despite this, increases in haemoglobin after treatment were higher with intravenous iron (median 1·55 (i.q.r. 0·93-2·58) versus 0·50 (-0·13 to 1·33) g/dl; P < 0·001), which was associated with fewer anaemic patients at the time of surgery (75 versus 90 per cent; P = 0·048). Haemoglobin levels were thus higher at surgery after treatment with intravenous than with oral iron (mean 11·9 (95 per cent c.i. 11·5 to 12·3) versus 11·0 (10·6 to 11·4) g/dl respectively; P = 0·002), as were ferritin (P < 0·001) and transferrin saturation (P < 0·001) levels. CONCLUSION: Intravenous iron did not reduce the blood transfusion requirement but was more effective than oral iron at treating preoperative anaemia and iron deficiency in patients undergoing colorectal cancer surgery.

The risk of oesophageal adenocarcinoma in a prospectively recruited Barrett's oesophagus cohort.

BACKGROUND: Varying rates of oesophageal adenocarcinoma (OAC) complicating Barrett's oesophagus (BO) have been reported. Recent studies and meta-analyses suggest a lower incidence, questioning the value of endoscopic surveillance. AIM: We aimed to retrospectively examine the rate of OAC, risk factors and causes of death in a prospectively recruited BO cohort. METHODS: Data from patients with BO from a cohort from 1982-2007 were studied. Patients were subdivided into surveyed, failed to attend surveillance and unfit for surveillance. Standardised mortality ratios (SMR) were calculated for common causes of death. Cox proportional hazards models were used to determine which factors were associated with progression to OAC. RESULTS: In total, 671 BO patients (61% male) were studied; 37 (76% male) were diagnosed with OAC. OAC incidence was 0.47% per annum and stable across three decades (1982-1991 0.56%, 1992-2001 0.46%, 2002-2012 0.41% (p = 0.8)). All-cause mortality was increased for the whole cohort (SMR 163(95% CI 145-183)). Mortality from OAC appeared higher in patients who failed to attend surveillance (SMR 3216(95% CI 1543-5916)) compared with surveyed (SMR 1753(95% CI 933-2998)) and those unfit for surveillance due to co-morbidity (SMR 440(95% CI 143-1025)). Multivariable analysis identified low-grade dysplasia (HR 4.4(95% CI 1.56-12.43), p = 0.005) and length of BO (HR 1.2(95% (1.1-1.3)), p < 0.001)) as associated with OAC. CONCLUSIONS: Progression to OAC appeared stable over three decades at 0.47% per annum. Patients with BO had a modest increase in all-cause mortality and a large increase in OAC mortality, particularly if fit for surveillance. Low-grade dysplasia and the length of the BO segment were associated with developing OAC.

Molecular logic of neocortical projection neuron specification, development and diversity.

The sophisticated circuitry of the neocortex is assembled from a diverse repertoire of neuronal subtypes generated during development under precise molecular regulation. In recent years, several key controls over the specification and differentiation of neocortical projection neurons have been identified. This work provides substantial insight into the 'molecular logic' underlying cortical development and increasingly supports a model in which individual progenitor-stage and postmitotic regulators are embedded within highly interconnected networks that gate sequential developmental decisions. Here, we provide an integrative account of the molecular controls that direct the progressive development and delineation of subtype and area identity of neocortical projection neurons.