Background
Colorectal carcinoma has a peak incidence in the seventh decade of life and patients often presents with comorbid iron deficiency anaemia. At least a third of patients with a colorectal carcinoma who undergo surgery, are anaemic preoperatively.
Anaemia in patients with colorectal carcinoma is partly caused by gastro-intestinal (GI) blood loss and is partly cancer-related. Cancer related anaemia is multifactorial and is caused by impaired iron absorption, nutritional deficiency and anaemia of chronic disease, which is a cytokine-mediated disorder. These effects cause functional iron deficiency, which is characterized by insufficient available iron at the site of erythroblast production (iron restricted erythropoiesis) with adequate iron stores. In addition, iron is an essential component of a large number of human metabolic enzymes, including ribonucleotide reductase and NADH dehydrogenase. Therefore iron deficiency even without concomitant anaemia is associated with fatigue, impaired physical performance and cognitive function.
Currently there are three options in the treatment of anaemia: blood transfusion, erythropoietin stimulating agents (ESA) and iron supplementation. Blood transfusion and ESA are effective modalities in increasing haemoglobin (HB) levels, however both modalities should be given with caution in oncologic patients as they are associated with an increased risk of cancer recurrence and ESA is even associated with an 17 % increase in overall mortality in oncologic patients.
With the application of laparoscopic surgery, blood loss is limited and blood transfusions are rarely necessary. In the LAFA study including 50 % open and 50 % laparoscopic segmental colectomies the blood transfusion rate was only 4 %. This decreasing rate of blood transfusion could be a reason for the moderate attention for the treatment of light to moderate anaemia in the preoperative setting. However it has been shown that preoperative anaemia, even to a mild degree, is independently associated with an increased risk of morbidity and 30-day mortality.
There is no standard of care in the treatment of light to moderate anaemia in the preoperative setting; some will have oral iron prescribed others not. A more profound treatment of iron deficiency anaemia could play a crucial role in optimizing patient's condition prior to surgery. Even tumour response on chemotherapy, as suggested by Lindsey, could be negatively influenced by low HB levels. In the Netherlands, average waiting time before surgery in case of a colorectal carcinoma is two to three weeks. This period could be used more effective in the optimisation of patients towards surgery. Studies on iron supplementation (both oral and intravenous) prior to orthopaedic and gynaecologic surgery showed that iron supplementation is effective in treating anaemia, reducing blood transfusions and also reducing length of stay.
However, in patients with colorectal carcinoma and concomitant anaemia current evidence on the role of iron supplementation seems inconclusive. This is due to methodological short comings of the studies, with small study populations, heterogeneity in iron preparations supplied, the lack of data on surgical outcomes and most importantly due to inclusion of both anaemic and non-anaemic patients. All of the above underlines the need for a new trial on the efficacy of pre-operative iron therapy in treatment of anaemia in patients with a colorectal carcinoma and its effect on outcomes after surgery.