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Optimisation of surgical care for rectal cancer
Borstlap, W.A.A.
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2017
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Borstlap, W. A. A. (2017). Optimisation of surgical care for rectal cancer.
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1
Preoperative iron therapy as treatment of anaemia
in patients with colorectal carcinoma;
a systematic review
W.A.A. Borstlap M.E. Stellingwerf Z. Moolla G.D. Musters C.J. Buskens P.J. Tanis W.A. Bemelman Colorectal Disease 2015Chapter 1 | Systematic review on iron therapy
Abstract
Aim:
Preoperative anaemia is associated with increased morbidity and mortality. The aim of this systematic review is to evaluate the efficacy of preoperative iron supplemen-tation in the treatment of anaemia, and its effect on the postoperative recovery of patients undergoing surgery for colorectal carcinoma.
Methods:
The systematic review was performed using MEDLINE, EMBASE and the Cochrane library to assess the current evidence on the role of iron supplementation in the treatment of preoperative anaemia. Our main outcomes were absolute haemoglo-bin increase, blood transfusion rate and postoperative morbidity. Main inclusion criteria were: preoperative iron supplementation, presence of colorectal carcinoma and elective surgery. The Downs-Black questionnaire was used for quality assess-ment of the included studies.
Results:
Of the 605 studies analysed, 7 studies comprising of 3 randomized controlled trials and 4 cohort studies were included. Despite iron supplementation, the 3 random-ized controlled trials showed a decrease in haemoglobin level. This was contrary to the 4 cohort studies which all showed a significant increase. All studies showed a decreased blood transfusion rate following iron supplementation. None of the included studies assessed postoperative morbidity. Due to heterogeneity in study design, duration of treatment, dosages and variety in iron substrates, we were un-able to perform a meta-analysis.
Conclusion:
In anaemic patients requiring surgery for colorectal carcinoma, current evidence is of inadequate quality to draw a definitive conclusion on the efficacy of the various alternatives to treat preoperative anaemia.
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Introduction
At least a third of patients with colorectal carcinoma (CRC) who require surgery are anaemic preoperatively.1 In clinical practice, however, little consideration is given
to correcting anaemia. Preoperative anaemia might potentially result in a higher rate of perioperative blood transfusion, an increase in perioperative morbidity and mortality and a prolonged recovery from surgery. Preoperative anaemia in a cohort of patients having noncardiac surgery was associated with an increased risk of 30-day morbidity and mortality.2 Furthermore, anaemia was a major predictive
factor for allogeneic blood transfusion (ABT). ABT is linked to established risks such as infection, incompatibility reactions and, most importantly, is associated with an increased incidence of recurrence of cancer.3,4
Recent studies on patients with CRC have shown the prevalence of anaemia and iron deficiency to be 40% and 60% respectively.4,5 In patients with CRC the cause
of anaemia is often multifactorial, but intestinal blood loss is the most common. Additional factors such as impaired iron absorption, nutritional deficiency and anae-mia of chronic disease, which is a cytokine-mediated disorder, may exacerbate the anaemia in patients with CRC5. Tumour cells can produce pro-inflammatory
cyto-kines resulting in suppression of erythroid progenitor cells, impaired erythropoietin production and iron utilization and decreased erythrocyte half-life.6
According to the Dutch Blood Transfusion Guideline7 there are three treatment
options in the management of anaemia, including allogenic blood transfusion (ABT), erythropoiesis stimulating agents (ESAs) and iron supplementation. ABT is associ-ated with an increased risk of recurrence of cancer and therefore should only be administered following careful consideration in patients with CRC.3,4 The use of ESA’s
is not recommended, as these are associated with a greater incidence of thrombosis and a 17% increase in overall mortality.8 Iron supplementation for the treatment of
anaemia is not associated with the negative effects on cancer recurrence, morbidity or mortality and has proven to be a cheap and save alternative option5,9, but its
efficacy in the preoperative setting has not been routinely established as iron takes longer to normalize the haemoglobin (Hb) level than ABT or ESA’s. We conducted this systematic review to assess current evidence on the efficacy of preoperative oral or intravenous (IV) iron supplementation in terms of an increase in haemoglo-bin, ABT and postoperative morbidity.
Chapter 1 | Systematic review on iron therapy
Methods
Search strategy
This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.10 The search
included studies on preoperative oral and/or IV iron supplementation in patients with CRC undergoing elective surgery. Studies comparing preoperative iron with any kind of ESA were also included, but only the study arm on iron supplemen-tation was analysed. To ensure a high sensitivity of the review, non-comparative and non-randomized observational studies were also included. The reference lists of included studies were crosschecked to identify additional studies. Studies that omitted details of the operation performed were excluded. In addition, studies that included patients who had received a blood transfusion in the month prior to surgery or were prescribed postoperative iron supplementation were also excluded. Systematic reviews, congress abstracts, animal studies, case reports (<10 patients) and articles not published in English were excluded.
Search
MEDLINE (PubMed), EMBASE (Ovid) and the Cochrane library were systematically searched. No restrictions with regard to publication date, patient age or technique of colorectal resection were applied. The final search was carried out in October 2014. The keywords and medical subject heading (MeSH) terms used for MEDLINE were: Colorectal carcinoma, surgery and iron (see appendix for detailed search terms).
Data extraction and analysis
Two reviewers independently assessed the identified studies based on their titles and abstracts. Full text articles were read by both reviewers. When required, the opinion of a third researcher was obtained. The study selection progress is displayed in Figure. 1. Patient Hb levels had to be measured prior to commencing iron supple-mentation and repeated within a day before surgery. The primary end-point was absolute change in Hb concentration between start of the treatment and the day of admission for surgery.
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Secondary outcomes were the percentage of patients requiring a blood transfu-sion, postoperative morbidity, length of hospital stay and adverse events after iron supplementation.
Validity assessment and assessment of eligibility
To assess the quality of the included studies, the Downs-Black questionnaire was used (table 5). This is a questionnaire commonly used for quality assessment for RCT’s as cohort studies11. The checklist consists of 27 items distributed between five
subscales including: (1) reporting of study findings (10 items), (2) external validity (three items), (3) bias (seven items), (4) confounding (six items) and (5) power (one item). Total scores using the original checklist range from 0 to 31 but, as in the studies of Handler et al. [12] and Chudyk et al.13, we modified the last question if
the study had made a power analysis from a scale of 0 to 5 to a scale of 0 to 1.The score was 1 if a power or sample size calculation was present and 0 if no power or sample size calculation was performed. Thus, our modified version ranged from 0 to 28, with a higher score indicating a higher quality of the study. A score greater or equal to 20 is considered as good, scores between 15 and 19 moderate, and scores of 14 and below poor. Table 3 shows the total scores of the different studies.
Results
Systematic search
The literature search produced 605 studies. After remocal of duplicates (n=110) and exclusions based on title (n=367) and abstract (n=111), 17 studies were selected for full text analysis. After a thorough search one full text study was not available, leaving 16 studies for analysis. After analysing the 16 full text publications, 9 were excluded for reasons given in Figure 1. Seven studies were included in the review, of which three were RCT’s14-16 and four were cohort studies.17-20 Of the latter, three
were prospective and one retrospective. All studies were published between 1999 and 2014. The study characteristics are summarized in Table 1 and 2.
Chapter 1 | Systemati c review on iron therapy
Records identified through database searching (n=604)
Additional records identified through other
sources (n=1)
Records after removal of duplicates (n=495)
Records screened (n=488)
Full-text articles assessed for eligibility
(n=16) Studies included in qualitative synthesis (n=7) Studies included in quantitative synthesis (RCT: n=3, OBS: n=4) Records excluded based on title/abstract (n=471)
Excluded based on full text (n=9) No patients with CRC analysed separately (n=1) No distinction between oral and IV (n=1)
No description of postoperative outcomes (n=1)
Blood transfusion before surgery (n=1) Descriptive article (n=2) Systematic review (n=3)
No abstract available (n=7)
No full text available (n=1) Id en tif ic at io n Sc re en in g El ig ib ili ty In cl ud ed Figure 1. Flow-diagram
Methodological quality assessment
Only the studies of Edwards et al.14 and Lidder et al.15 complied with the
require-ments of good studies (Table 5). All other studies were considered moderate, except that of Bisbe et al.19, which was assessed to be of poor quality.
Increase of haemoglobin
Despite preoperati ve iron supplementati on, a decrease in Hb level was seen aft er iron supplementati on in all three included RCT’s. The trials of Edwards et al.14 and
Lidder et al.15 compared placebo with IV and oral iron, respecti vely. A greater
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compared to patients who received iron therapy (-0.19 g/dl and -0.3 g/dl), P-values for these differences were not provided (Table 3). Both these trials also included non-anaemic patients. The RCT of Qvist et al.16 included anaemic patients. They
randomized patients into three groups including two that received a different dose of Recombinant Human Erythropoietin (EPO) and a third group that received a placebo in combination with four days of oral iron. We only included the outcome of the third group that demonstrated a decrease in Hb of 0.6 within four days of iron supplementation.
The four included cohort studies demonstrated a significant increase in the level of Hb from start of iron supplementation to surgery (Table 2).17-20 The cohort studies
of Bisbe et al.19 and Keeler et al.18 showed a significant Hb-level increase of 2.5 g/dl
(1.55 mmol/L, p <0.05) and 1.65 g/d (l.02 mmol/L, p <0.01).
Okuyama et al.17 compared preoperative oral iron supplementation with
a placebo in anaemic patients and showed a significant increase in Hb of 2 g/dL (1,24 mmol/L) compared with a mean rise of 0.9 g/dl in the placebo group. The observational cohort study of Quinn et al.20, which was the only cohort study that
also included nonanaemic patients, showed a significant increase in Hb of 1.2 g/ dL (0,75 mmol/L, p <0.001) after supplementation for at least 14 days (median 39 days). Analysis of the anaemic subgroup of 58 patients identified a mean increase in Hb of 1.73 g/dL (1,08 mmol/L) (P<0,001) compared to 0,46 g/dL (0,29 mmol/L) in the nonanaemic group (table 4).
Blood transfusion
Based on the results of the RCT’s, the percentage of patients receiving an ABT varied from 14.7% to 71.4%. The trial of Edwards et al.14 showed a trend towards a lower
percentage of patients receiving an ABT in the iron-supplemented group compared with patients who received a placebo (14.7% vs. 19.2%, Table 3). In the anaemic subgroup the difference was 22% (iron) compared with 56% (placebo), however this difference was not statistically significant.
In the study of Lidder et al.15, the percentage of patients that required an ABT was
significantly lower following iron supplementation (26% vs. 59%; P=0.05). Analysis of the anaemic subgroup revealed that 59% of patients who received iron required an ABT compared with 71.4% of patients who did not, although no p-value was staed (Table 3). The study carried out by Okuyama et al.17 was the only cohort study
Chapter 1 | Systematic review on iron therapy
with a control group that did not receive iron, and the authors found a significant difference in the percentage of patients receiving ABT compared to the placebo group (9.4% vs. 27.4%;P<0.05).
Morbidity
The only study that analysed postoperative morbidity was the small noncomparative study of Keeler et al.18 Length of stay was measured in four of the seven studies14-16,18
but the differences in length of stay were not significant in any of them.
Discussion
The present review focussed on three important considerations for the implemen-tation of preoperative iron supplemenimplemen-tation into current practice. These included efficacy in terms of Hb-increase, its influence on morbidity and the rate of ABT. The review revealed contradictory results on the benefit of preoperative iron in anaemic CRC patients in contrast to orthopaedic and gynaecologic studies.21-23 In these
stud-ies preoperative iron supplementation proved to significantly increase the level of Hb significantly and to reduce the rate of ABT and length of hospital stay.
All three RCT’s all showed a decrease in the level of Hb after the initiation of iron therapy. This was in contrast to the four cohort studies which all showed a significant increase. The decrease could be explained by the design of the studies. In the trials of Edwards et al.14 and Lidder et al.15 nonanaemic patients were included, possibly
skewing positive results in anaemic patients. The efficacy of iron therapy on the level of Hb in nonanaemic patients is minimal, as these patients do not have a restriction in erythropoiesis based on iron deficiency. In order to make firm conclusions about preoperative iron therapy, RCTs focussing exclusively on anaemic patients are need-ed. A possible explanation for the inclusion of nonanaemic patients is the difficulty of obtaining approval of the ethics committee for a trial in which a treatment with known benefits is deliberately withheld from a group of patients. Another reason might be the use by Edwards et al.14 of a fixed dose of IV iron sucrose
supplementa-tion, whereas current guidelines recommend that the dose should be adjusted to level of Hb and to the weight of the patient.24 The decrease in the Hb level observed
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short duration of the iron therapy (4 days). The normal response time for oral iron to increase the HB level by 2.0 g/dl is 3-4 weeks.25
The blood transfusion rate was consistently higher in patients without preopera-tive iron supplementation. In the studies of Edwards et al.14 and Lidder et al.15 the
rate were relatively high (19% and 59% respectively) since in centralized centres transfusion rates may be as low as 4%1. Colorectal surgery is becoming less invasive
and the low ABT rate raises the question whether blood transfusion is the most relevant clinical endpoint in relation to treatment of preoperative anaemia.
Unfortunately, postoperative morbidity was poorly assessed in the included studies.
In general surgery, preoperative anaemia negatively affects morbidity and mor-tality after surgery.2,26,27 Musallam et al.2 showed in a retrospective cohort study
on 227425 patients undergoing noncardiac surgery that even mild anaemia was independently associated with higher postoperative morbidity. However, they did not specify the number of patients with CRC in this cohort.
Several side effects have been described following the administration oral and IV iron. The incidence of anaphylactic shock following IV iron has been reduced with the introduction of newer IV substrates such as ferric carboxymaltose which have resulted in a reported incidence of <0.1%.28 No anaphylactic reactions were
reported in any of the included studies. With a low incidence of adverse events (a total of three events) we conclude that iron supplementation, both oral and IV seems to be harmless.
None of the included studies reported on compliance to oral iron supplementa-tion. It is known, however, that gastrointestinal side effects and the unpleasant taste of oral iron supplements reduce compliance. Intravenous iron reduces noncompli-ance, but the potential advantages of cost, efficacy and safety in the preoperative period require further investigation.
Including only Level 1 evidence is preferable when conducting a systematic re-view is to be desired, but the included RCTs were influenced by several confounders. Two14,15 out of three RCTs mainly included nonanaemic patients and the third16 gave
oral iron for only four days. The conclusions based on the RCTs would not have been sufficient and for this reason the cohort studies were included in the present systematic review.
Chapter 1 | Systematic review on iron therapy
Based on current available data, no conclusion can be drawn on the efficacy of preoperative iron supplements in patients undergoing surgery for a colorectal carcinoma. This is due to the methodological shortcoming of the studies, including small population size, variation in the iron preparations used, lack of standardiza-tion of dosage, variastandardiza-tion in treatment periods and the inclusion of anaemic and nonanaemic patients. It was not possible, therefore, to perform a meta-analysis. The secondary end-point of length of stay and postoperative morbidity, were not adequately investigated in the included studies.
Two of the three options for treating preoperative anaemia, namely ABT and ESAs, are associated with a higher incidence of recurrence of cancer and increased morbidity.3,4,8
Currently there is a paucity of information in the literature regarding the third treatment option, namely iron supplementation. Despite this lack on evidence, oral iron is being recommended in current guidelines as treatment of preoperative anaemia.7,29,30
The present study highlights the lack of conclusive data on the relation between iron supplementation and any effect on postoperative anaemia, morbidity, tumour recurrence, cost and quality of life of patients with CRC.
It is important to use the period before to elective colorectal surgery to optimize a patients’ physiological status, but more data are necessary to establish the differ-ent alternatives of iron supplemdiffer-entation.
Author contributions
W. Borstlap, M. Stellingwerf and G. Musters contributed to the literature review of this manuscript. All authors contributed to finalization of the manuscript. W. Borstlap and M. Stellingwerf contributed equally to the complete manuscript.
Conflict of interest
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Table 1. Pa tien t and s tudy char act eris tics of R CT s tudies Re fer ence Cohort size Ag e (median) In ter ven tion Per cen tag e of anaemic patien ts (%)Tumour stadia; Duk
es’ (%)
Tumour localisa
tion (%) Neoadjuv an t ther ap y Rele van t endpoin ts Sur gic al pr ocedur e Edw ar ds et al . 60 67 IV IS: 34 26% a Not report ed Not r eport ed Yes Chang e in Hb concen tra tion, trans fusion r at e, chang es in serum iron mark er s, leng th of s ta y and adv er se perioper ativ e e ven ts. Resectional sur ger y 70 Placebo: 26 35% Lidder et al. 45 69 (r ang e 47-69) Or al f err ous sulpha te: 23 25% a A: 4,3, B: 34,8, C: 56,5 Not r eport ed Not r eport ed Chang e in Hb and ferritin c oncen tra tion, re ticulocy te c oun t, es tima
ted blood loss,
blood tr ans fusion requir emen ts and leng th of s ta y. An terior r esection (n=12), A-P r esection (n=2), le ft hemi (n=2), righ t hemi (n=5) 72 (r ang e 57-80) No ir on: 22 : 14) 56%% A: 13,6, B: 31,8, C: 50 An terior r esection (n=13), A-P r esection (n=1), righ t hemi (n=8), sub tot al colect om y (n=1) Qvis t e t al. 81 69 (r ang e 48-86) ES A: 38 100% Not report ed Not r eport ed Not r eport ed Hb c oncen tra tion a t
various time poin
ts.
Number of blood trans
fusions. Incr ease in r eticulocy te c oun t. Adv er se e ven ts. LAR (n=13), r ect al ex tirpa tion (n=3), other colonic r esection (n=22), pallia tiv e c olos tom y (n=5) 69 (r ang e 40-85) Or al ir on: 43 100% a Hb le vel a t leas t 13·5 g /dl in males and 12·5 g /dl in f emale
Chapter 1 | Systematic review on iron therapy Table 2. Pa tien t and s tudy char act eris tics of Cohort s tudies. Re fer ence No. pa tien ts Ag e (median) In ter ven tion Per cen tag e of anaemic patien ts (%) Tumour stag e; Duk es’ (%) or TNM
Tumour localisa
tion (%) Neoadjuv an t ther ap y Rele van t endpoin ts Sur gic al pr ocedur e Bisbe et al. 24 45 65 (r ang e 36-87) IV F CM: 15 100% Not r eport ed Not r eport ed Not r eport ed Eff ects on Hb and aneamia c orr ection.
Number of blood trans
fusions and adv er se e ven ts. Ir on tr ea tmen t c os ts. Major electiv e sur ger y Ok uy ama et al. 22 116 Mean 68,9 (SD 9,6) Or al f err ous citr at e: 32 100% A: 9,4,: B:40,6, C:25, D: 25 C: 12,5, A: 43,8, T : 6,3, S: 21,9, R: 15,6 Not r eport ed Chang e in Hb and hema tocrit le vels, in traoper ativ e blood loss and tr ans fusion ra te. Ileocec al r esection, righ t/ le ft/tr ans ver se/ sigmoid/ sub tot al/t ot al c olect om y, an terior r esection, Hartmann pr ocedur e, in tes tinal b ypass sur ger y colos tom y Mean 67,7 (SD 11,2) No ir on: 84 100% 0: 1,2, A: 1,2, B: 41,7, C:31, D:21,4, Unkno wn: 3,6 C: 13,1, A: 27,4, T : 13,1, D: 8,3, S: 22,6, R: 15,5 Quinn et al. 23 103 (a*: 58) M: 68 (44- 88), F: 62 (37-86) Or al f err ous sulpha te: 103 56% Not r eport ed Righ t: 23,3, le ft: 26,2, R: 48,5 Not r eport ed Chang e in Hb and trans fusion r at e. St andar d open pr ocedur e Keeler et al. 20 20 77 (36-85) IV F CM: 18 100% T1: 5, T2: 25, T3: 60, T4: 10, Not r eport ed Not r eport ed
Feasibility of a single 15 minut
e IV in fusion, chang e in Hb and ARB T. Pot en tial pr edict or s of r esponce, me thods of selection of candida tes. (Ex tended) righ t hemic olect om y (& sigmoid c olect om y), an terior r esection, panpr oct oc olect om y.
Open and lapar
osc opic access. FCM: F erric c arbo xymalt
ose; C: Cecum; A: Ascending; T
: T
rans
ver
se; D: Descending; S: Sigmoid; R: R
ectum; M: male; F: f emale; SD: s tandar d de via tion.* Quinn et al. 23 used participan ts with diff er en t Hb le vels, ther ef or e the
y made an anaemic (a) subgr
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Table 3. Main out comes Randomiz ed Con trolled trials Re fer ence In ter ven tion Dose Dur ation (median) Hb a t recruitmen t ( g/ dL) (mean) Mean Hb rise ( g/dL) P-in ter val AB T (%) P-in ter val Blood trans fusion policy Tr ea tmen t rela ted adv er se ev en ts Edw ar ds et al. IV 2x300mg 17 da ys (rang e 11- 32) 13,4 (SD 2.4) (a: 11,7 (SD 0.6)) -0,19 (a: -0,46) 0,355 14,7 (n=5) a: 22 (n=2) 0.335 Hb <8 g /dl or 8-10 g /dl with c ar diac/ respir at or y disease, opinion anaes the tis t 5.8% (2/34) Symp toma tic hypot ense Lidder et al. Placebo 200mg unkno wn 13,7 (SD 0.5) (a: 11,8 (SD 0.9)) -0,5 (a: -0,11) NS 19,2 (n=5) a: 56 (n=5) Or al ir on 200mg 14 da ys (rang e 12- 56) 13,4 (SD 1,9) -0,3 NS 26 (n=6) a: 50 (n=3) 0.0471 Hb <8 g /dl or 8-10 g /dl with c ar diac/ respir at or y disease, opinion anaes the tis t Not r eport ed Qvis t e t al. No ir on 12,4 (SD 2,1) -0,6 0,002 59 (n=13) a: 71,4 (n=10) Or al ir on 200mg 4 da ys Median 12,2 (rang e 8,2-13,7) -0,6 -53,0 (n=23) Opinion anaes the tis t and sur geon 0% (0/81)Chapter 1 | Systematic review on iron therapy Table 4. Main out comes of Cohort s tudies Re fer ence In ter ven tion Dose Dur ation (median) Hb a t recruitmen t ( g/ dL) (mean) Mean Hb rise ( g/dL) P-in ter val AB T (%) P-in ter val Blood tr ans fusion policy Tr ea tmen t rela ted adv er se ev en ts Bisbe et al. IV F CM FCM (500-1000 mg , 3 ± 1 doses)
Mean 3 times (sd 1), leng
th unkno wn Mean 9,2 (SD 1.0) 2,5 (SD 1,3) <0.05 7,0 (n=1) -Not r eport ed 1/45 (7%) “mild se ver e ev en t” , unspecified Ok uy ama et al. Or al ir on Ferr ous citr at e (200 mg /d) ≥ 2 wk Mean 8,1 (SD 1,4) 2.0 <0.05 9,4 (n=3) <0.05 In traoper ativ e Hb of 7 g /dl with uns table hemodynamics Not r eport ed No ir on No ir on Mean 8 (SD 1,6) 0,9 27,4 (n=23) Quinn et al. Or al ir on FS (200 mg 3x/d), short -cour se <14d, long-c our se >14d 39 da ys (rang e 7-63) Mean 12 (10-13,9) (a*: 10,2, IQR 9-12) 1,2 (a: 1,7) <0,001 <0,001 20,6 (n=20) -Hb <8 g /dl or >8 g / dl in e xcep tional cir cums tances such as c ar diac ischaemia 0/116 (0%) Keeler e t al. IV FCM (1000 mg , 1 dose) 27,5 da ys (rang e 16-43) Male: 9,25 (6,7- 11,9), F emale: 10,2 (4,6-11,7) Median 1,65 <0,001 20% (n=4) -Hb <7 g /dl, <9 g / dl with c ar diac/ respir at or y
disease, opinion clinic
al t eam 0/20 (0%) IV : In tra venous; F CM: F erric c arbo xymalt ose; AB T: Allog eneic blood tr ans fusion
1
Table 5. Down-Black Quality assessment. Bisbe
et al.24 Edwards et al.19 Lidder et al.20 Okuyama et al.22 et al.Quinn 23 et al.Qvist 21 Keeler et al.20
Reporting 6/10 9/10 9/10 9/10 8/10 10/10 9/10 1. Hypothesis 2. Main outcomes 3. Patients 4. Intervention 5. Confounders(2 points) 6. Main findings 7. Variability 8. Adverse events 9. Follow up External validity 1/3 2/3 2/3 1/3 2/3 0/3 2/3 10. P-values 11. Representative .1 12. Representative .2 Bias 3/8 8/8 6/8 4/8 6/8 6/8 5/8 13. Hospitals
14. Blinding study subjects 15. Blinding those measuring 16. Retrospective 17. Length of follow up 18. Statistical tests 19. Compliance 20. Accurate Confounding 0/6 6/6 4/6 3/6 2/6 2/6 1/6 21. Selection 22. Time period 23. Random 24. Concealment 25. Confounding 26. Loss to follow up Power 0/1 1/1 1/1 0/1 0/1 0/1 0/1 27. Power Total score 10/28 26/28 22/28 17/28 18/28 18 15/28
Quality Low Good Good Moderate Moderate Moderate Moderate
Chapter 1 | Systematic review on iron therapy
Search terms:
(“Colorectal Neoplasms”[Mesh] OR colorectal neoplasm*[tiab] OR colorectal cancer*[tiab] OR colorectal carcinoma*[tiab] OR colorectal tumor*[tiab] OR CRC[tiab] OR colon cancer*[tiab] OR colonic cancer*[tiab] OR colon neoplasm*[tiab] OR colonic neoplasm*[tiab] OR cancer of the colon[tiab] OR rectal cancer*[tiab] OR rectum cancer*[tiab] OR rectal neoplasm*[tiab] OR rectum neoplasm*[tiab] OR rec-tal tumor*[tiab] OR rectum tumor*[tiab] OR cancer of rectum[tiab]) AND (“General Surgery”[Mesh] OR “Surgical Procedures, Operative”[Mesh] OR surgery*[tiab] OR resection*[tiab] OR “surgery”[Subheading]) AND (Iron[Mesh] OR ferritins[Mesh] OR iron*[tiab] OR ferric[tiab] OR ferrous[tiab]).
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