ORIGINAL ARTICLE
Fe ic ca boxymal ose educes ans usions and hospi al s ay
in pa ien s wi h colon cance and anemia
José Luis Calleja
1
&Sal ado a Delgado
2
&Adol o del Val
3
&An onio He ás
4
&
José Luis La aona
5
&Ál a o Te án
6
&Me cedes Cucala
7
&Fe mín Mea in
8
&
on behal o he Colon Cance S udy G oup
Accep ed: 19 No embe 2015 /Published online: 22 Decembe 2015
#The Au ho (s) 2015. This a icle is published wi h open access a Sp inge link.com
Abs ac
Pu pose The pu pose o he s udy was oe alua e he e icacy
o p eope a i e in a enous (IV) e ic ca boxymal ose (FCM)
adminis a ion s. no-IV i on in colon cance (CC) anemic
pa ien s unde going elec i e su ge y wi h cu a i e in en ion.
Me hods This was a mul icen e , obse a ional s udy includ-
ing wo coho s o consecu i e CC anemic pa ien s: he no-IV
i on ea men g oup was ob ained e ospec i ely while
FCM- ea ed pa ien s we e eco ded p ospec i ely.
Resul s A o al o 266 pa ien s we e included: 111 ecei ed
FCM (median dose 1000 mg) and 155 we e no-IV i on sub-
jec s. Bo h g oups we e simila in e ms o demog aphic cha -
ac e is ics, umo loca ion, su gical app oach, and in a-
ope a i e bleeding se e i y. The FCM g oup showed a signi -
ican lowe need o ed blood cell (RBC) ans usion du ing
he s udy (9.9 s. 38.7 %; OR: 5.9, p<0.001). In spi e o lowe
hemoglobin le els a baseline diagnosis and lowe ans usion
a es in he FCM g oup, he p opo ion o esponde s was
signi ican ly highe wi h espec o he no-IV g oup bo h a
hospi al admission (48.1 s. 20.0 %, p<0.0001) and a 30 days
pos -su ge y (80.0 s. 48.9 %, p<0.0001). The pe cen age o
pa ien s wi h no malized hemoglobin le els was also highe in
he FCM g oup (40.0 s. 26.7 % a 30 days, p<0.05). A lowe
numbe o ein e en ions and pos -su ge y complica ions
we e seen in he FCM g oup (20.7 s. 26.5 %; p=0.311).
The FCM g oup p esen ed a signi ican sho e hospi al s ay
(8.4±6.8 s. 10.9±12.4 days o discha ge; p<0.001).
Conclusions P eope a i e e ic ca boxymal ose ea men in
pa ien s wi h CC and i on de iciency anemia signi ican ly e-
duced RBC ans usion equi emen s and hospi al leng h o
s ay, eaching highe esponse a es and pe cen ages o no -
malized hemoglobin le els bo h a hospi al admission and
30 days pos -su ge y.
Keywo ds I on de iciency anemia .Colon cance su ge y .
I on in a enous adminis a ion .Fe ic ca boxymal ose
In oduc ion
A la ge numbe o di e en umo s occu associa ed wi h ane-
mia, which anges om 25–75 % in cance pa ien s who un-
de go su ge y [1]. Al hough di e ing by umo loca ion, he
o e all p e alence o anemia in colon cance was a ound 48 %
The Colon Cance S udy G oup also includes Jesús-Albe o Va ela
(Hospi al G ego io Ma añón, Mad id, Spain), Te esa B oque as
(Hospi al del Ma , Ba celona, Spain), F ancisco-Ja ie Es eban (Hospi al
La Paz, Mad id, Spain), Luis Fe e (Hospi al Gene al Uni e si a io, Va-
lencia, Spain), Lau a Sanchis (Hospi al Gene al Uni e si a io, Valencia,
Spain), Fede ico A güelles (Hospi al Vi gen de la Maca ena, Se illa,
Spain), and Mon se a And eu (Hospi al del Ma , Ba celona, Spain).
*José Luis Calleja
[email protected]
1
Diges i e Diseases Depa men , Hospi al Pue a de Hie o, Calle
Manuel de Falla 1, Majadahonda 28222, Mad id, Spain
2
Gas oin es inal Su ge y Depa men , Hospi al Clínic,
Ba celona, Spain
3
Diges i e Diseases Depa men , Hospi al La Fe, Valencia, Spain
4
Diges i e Diseases Depa men , Hospi al Reina So ía,
Có doba, Spain
5
Diges i e Diseases Depa men , Hospi al Nues a Seño a de Valme,
Se illa, Spain
6
Diges i e Diseases Depa men , Hospi al Ma qués de Valdecilla,
San ande , Spain
7
Medical Depa men , Vi o Pha ma España, Ba celona, Spain
8
Diges i e Diseases Depa men , Cen o Médico Teknon,
Ba celona, Spain
In J Colo ec al Dis (2016) 31:543–551
DOI 10.1007/s00384-015-2461-x
wi h mode a e o se e e anemia ound in mo e han 20 % o
cases [2]. The e iology o anemia in cance pa ien s is ypically
mul i ac o ial, mainly caused by sys emic in lamma ion wi h
inc eased hepcidin le els p omo ed by he umo i sel as well
as by i on de iciency due o gas oin es inal blood loss ha
occu s in associa ion wi h umo ulce a ion and wi h malnu-
i ion de i ed om he disease i sel [3,4]. Besides, blood
losses can be s essed du ing he su ge y.
P eope a i e anemia is eme ging as a common and impo -
an heal h p oblem [5]. This condi ion is ex emely common
be o e su ge y associa ed wi h colo ec al cance (up o 70 %
o pa ien s) [6,7] and has also been demons a ed in associa-
ion wi h inc eased pos ope a i e mo bi-mo ali y and du a-
ion o hospi aliza ion as well as wi h educed quali y o li e
[5,7–10]. Anemia migh con ibu e o complica ions du ing
and pos -su ge y [6,7,9]. In addi ion, a low p eope a i e
hemoglobin concen a ion is one o he majo isk ac o s o
ans usion in su ge y wi h mode a e o high blood losses [5,
6,10]. Join ly, he pe iope a i e ans usions un a o ably a -
ec pa ien ou comes and highligh he isk o pos ope a i e
in ec ions, su gical ein e en ion, ecu ence-me as asis, and
subsequen cance - ela ed mo ali y in colo ec al cance su -
ge y [6,11,12]. The e o e, in he con ex o elec i e su ge y, i
is ad isable as a as possible o de ec and e alua e p eope -
a i e anemia ea ly enough o s a a sui able ea men .
Anemia in his pa ien popula ion is la gely due o absolu e
o unc ional i on de iciency. As such, adminis e ing i on p io
o su ge y is conside ed an app op ia e ea men [13,14].
Mos anemic pa ien s a e ea ed wi h o al i on, al hough his
he apeu ic p ocedu e is slow in e ms o i on abso p ion a e
and, in he con ex o a su gical cance pa ien , clea ly insu -
icien o es o e ea ly enough he hemoglobin le els and o
i on deposi eposi ioning [14,15]. Howe e , pa en e al ad-
minis a ion o i on could inc ease up o i e imes he e y h-
opoie ic esponse, which is also associa ed wi h a lowe e-
quency o ad e se e ec s in compa ison wi h blood ans u-
sions [13,16,17].
P e ious s udies ha e shown ha ea men wi h in a e-
nous i on adminis e ed a leas 1 week be o e su ge y in-
c eases hemoglobin le els and, consequen ly, should educe
he need o ans usion o ed blood cell (RBC) uni s du ing
he pe iope a i e pe iod [18–20]. The e o e, he implemen a-
ion o in a enous i on adminis a ion p o ocols appea s o be
an e ec i e and sa e s a egy o he ea men o p eope a i e
anemia and possibly o educe ans usion equi emen s and
hospi aliza ion in pa ien s scheduled o elec i e su ge y while
mee ing cos -e ec i eness c i e ia, whene e an ea ly de ec-
ion and diagnosis o p eope a i e anemia is achie ed wi h he
objec i e o implemen his he apeu ic choice [13,14,21].
Many unsus ained misconcep ions cons i u e a ba ie o his
app oach [15].
Wi h his backg ound in mind and conside ing he lack o
s udies wi h a signi ican numbe o pa ien s wi h colon cance
(CC), his s udy was designed o e alua e he e icacy o a
p eope a i e adminis a ion p o ocol o in a enous (IV) e ic
ca boxymal ose (FCM) in colon cance pa ien s wi h i on de-
iciency anemia. E alua ion was comple ed by assessing he
ela i e educ ion in RBC ans usion equi emen s, pos -
su ge y complica ions (1 mon h a e su ge y), and he o al
leng h o hospi al s ay compa ed wi h a e ospec i e coho o
pa ien s ha had no ecei ed IV i on.
Ma e ial and me hods
This is a non-in e en ional s udy conduc ed in Spain as a
mul icen e su ey in ol ing wo coho s o consecu i e pa-
ien s wi h colon cance and i on de iciency anemia. A diag-
nosis, he compa a o g oup wi h no-IV i on ea men (no-IV
i on g oup)was ob ained e ospec i ely while pa ien s ea ed
wi h e ic ca boxymal ose (FCM g oup) (Fe injec ®; Vi o
Pha ma España S.L.) we e eco ded p ospec i ely.
Inclusion o p ospec i e pa ien s was comple ed be ween
Feb ua y 2012 and Sep embe 2012 in a specialized hospi al
se ing a 11 Spanish hospi als. In he same pa icipan cen e s,
he e ospec i e coho was ob ained in a sequen ial manne
om su gical in e en ion 2011 egis ies and independen ly
o ou comes. All subjec s ga e hei in o med consen p io o
hei inclusion in he s udy. App o al by he app op ia e
Ins i u ional Re iew Boa ds was ob ained.
The s udy popula ion in bo h g oups included pa ien s aged
18 yea s o o e , diagnosed wi h colon adenoca cinoma loca -
ed a leas 15 cm abo e he anal ma gin, wi h elec i e su ge y
p og ammed unde cu a i e pu poses. I on de iciency anemia
was de ined acco ding o WHO c i e ia (hemoglobin (Hb)
<13 g/dL in men and <12 g/dL in women) [22], se um e i in
<30 ng/mL, and/o ans e in sa u a ion index <20 %. The e
we e no es ic ions on he su gical app oach (lapa oscopy,
open su ge y, single po , e c.). The s udy excluded pa ien s
who had ec al neoplasms, eme gency o pallia i e su ge y,
o he linked illnesses associa ed wi h anemia such as enal
ailu e o hema ological synd omes, umo ecu ence, o a
clinical his o y o blood ans usions du ing he pas 30 days.
The p ima y ou come o he s udy was he ela i e educ-
ion in pe iope a i e and a 30-day pos ope a i e allogenic
RBC ans usion equi emen s. The seconda y end poin s in-
cluded he educ ion o hospi al leng h o s ay (o ime o
discha ge), he incidence o pos ope a i e complica ions eg-
is e ed du ing he i s mon h a e su ge y, he e olu ion o
hemoglobin and i on pa ame e s du ing he s udy pe iod, and
he p opo ion o pa ien s wi h no malized Hb le els and e-
sponse a e.
The physicians esponsible o he pa ien s’ca e, su ge y,
hospi al discha ge, and ollow-up we e unawa e o s udy in-
e en ions. When he cen e diagnosed a pa ien wi h colon
cance and concu en i on de iciency anemia, and who
544 In J Colo ec al Dis (2016) 31:543–551
me all he selec ion c i e ia, he in es iga o eques ed he
inclusion o he pa ien in he p og am o IV i on wi h e ic
ca boxymal ose adminis a ion. The o al dose was ob ained
using he e ic ca boxymal ose p oduc in o ma ion dosing
scheme [16,17]. Whene e possible, he FCM adminis a ion
was be ween 2 and 4 weeks be o e he scheduled su ge y.
As s anda dized hospi al clinical p ac ice, a comple e blood
es was also pe o med a diagnosis, he day o admission o
su ge y, a discha ge, and a 30 days pos -su ge y. Pe i- and
pos ope a i e RBC ans usions we e based on he pe inen
blood es s and as in hospi al clinical p ac ice: being always
pe o med in pa ien s wi h hemoglobin le els unde 7 g/dL,
unde physician c i e ia be ween 7 and 9 mg/dL, and no ec-
ommended o e 9 g/dL. No malized Hb le els we e
es ablished as ≥12 g/dL in women and ≥13 g/dL in men
[22]. Pa ien esponse was conside ed when Hb inc eases
≥1.5 g/dL.
Based on he p ima y end poin , he calcula ed sample size
o he s udy was app oxima ely 111 pa ien s pe g oup. This
es ima ed size allows he de ec ion o a leas a 20 % educ ion
in RBC ans usion equi emen s wi h a s a is ical powe o
90 % and using a 95 % con idence in e al (CI). Con inuous
end poin s we e summa ized using desc ip i e s a is ics: n,
mean, s anda d de ia ion, minimum, median and maximum,
95 % CI, and numbe o missing obse a ions. Fo disc e e
end poin s, he equency and pe cen age o each esponse
ca ego y we e calcula ed as well as 95 % CI and numbe o
missing da a. Missing da a was excluded when calcula ing
pe cen ages ela i e o he o al sample. S uden es o
Mann-Whi ney U es we e used depending on dis ibu ion
o a iables.
Resul s
Baseline and clinical cha ac e is ics
Baseline cha ac e is ics we e simila o bo h coho s
s udied (Table 1). In o al, 266 pa ien s we e included:
111 ecei ed FCM (57.3 % males, mean age 72.9±11.1)
and 155 we e in he no-IV i on g oup (55.8 % males,
mean age 70.8±10.3). Bo h g oups we e simila in e ms
o umo loca ion, medical his o y, and su gical app oach
and p ocedu es, as well as he p opo ion o pa ien s wi h
mode a e o hea y blood loss (≥50 mL) du ing su ge y
(Table 1). Anemia a diagnosis was mo e p onounced in
he FCM g oup.
All pa ien s in he e ospec i e coho (no-IV i on g oup)
we e ecei ing di e en doses and o mula ions o o al i on
supplemen a ion a he ime o diagnosis. Wi hin he p ospec-
i e coho , he median o al FCM dose was 1000 mg i on
(mean 1275±430.1 mg) and he adminis a ion was 28.5±
16.7 days be o e su ge y (mean±SD).
Table 1 Baseline, clinical, and su gical cha ac e is ics o he pa ien s
No-IV i on FCM p
Numbe , N155 111
Sex, male (%) 55.8 57.3 0.817
Age, yea s (mean±SD) 70.8±10.3 72.9±11.1 0.121
BMI, kg/m
2
(mean±SD) 28.2±4.9 27.7±5.7 0.429
ASA (%) 0.088
I11.65.6
II 42.2 56.5
III 44.2 35.2
IV 2.0 2.8
Pas medical his o y (%)
Diabe es 35.7 29.2 0.276
Hype ension 56.2 56.0 0.968
EPOC 12.3 13.9 0.713
Hea disease 19.1 22.6 0.486
An icoagulan he apy 7.9 15.7 0.050
Tumo loca ion (%) 0.846
Ascending colon 55.6 59.2
T ans e se colon 9.2 6.8
Descending colon 8.5 9.7
Sigmoid colon 26.8 24.3
Symp oma ology (%) 0.181
Rec o hagia 23.2 27.0
Obs uc ion 2.6 2.7
Pain 16.8 9.9
Anemic symp oms 43.2 36.9
None 14.2 23.4
I on ea men a diagnosis (%)
O al 100.0 15.3
Fe ic ca boxymal ose 0.0 100.0
Su gical app oach (%) 0.105
Open su ge y 52.6 42.7
Lapa oscopy 47.4 54.5
Single-po su ge y 0.0 0.9
NOTES 0.0 1.8
Su gical in e en ion (%) 0.838
Righ hemicolec omy 61.4 64.0
Sigmoidec omy 24.1 21.0
Le hemicolec omy 9.0 11.0
Segmen al esec ion 5.5 4.0
In aope a i e blood losses (%) 0.857
Low 47.1 43.3
Mode a e (≥50 ml) 44.2 46.3
High (>250 ml) 8.7 10.4
In aope a i e mode a e/se e e blood losses (%)
Open su ge y 62 73 0.356
Lapa oscopic 43 39 0.817
ASA Ame ican Socie y o Anes hesiologis s, BMI body mass index,
EPOC excess pos -exe cise oxygen consump ion, FCM e ic
ca boxymal ose, NOTES
In J Colo ec al Dis (2016) 31:543–551 545
P ima y ou come: ans usion equi emen s
A signi ican ly lowe pe cen age o pa ien s in he FCM
g oup equi ed allogenic RBC ans usion du ing he
s udy: 9.9 s. 38.7 % (OR: 5.9, 95 % CI: 2.9–11.1,
p<0.001). This s a is ically and clinically signi ican di -
e ence was also obse ed in he indi idual pe i- and
pos -su ge y pe iods un il day 30 and independen ly o
he ype o su gical app oach (lapa oscopic o open su -
ge y) (Table 2). O e all, he mean numbe o RBC uni s
ans used du ing he s udy pe iod was s a is ically lowe
in pa ien s ea ed wi h FCM (0.2±0.5 s. 0.8±0.4,
p<0.0001) (see Table 2 o pe i- and pos -su ge y pe-
iods). When analyzed by su ge y, FCM- ea ed pa ien s
ecei ed s a is ically signi ican lowe mean uni s o
RBC as well (Table 2). Th oughou he en i e s udy pe-
iod, 9 % o pa ien s in he no-IV i on g oup ecei ed 4
o mo e RBC uni s s. 0 % in he FCM g oup (p=
0.5817).
E olu ion o hemoglobin and i on me abolism pa ame e s
All he hema ological pa ame e s, excep se um e i in and
ans e in sa u a ion index a hospi al discha ge, p esen ed
signi ican di e ences be ween he FCM and no-IV i on
g oups a admission ime poin and 1 mon h a e su ge y
(Table 3,Fig.1). Impo an ly, he FCM g oup ecei ed o e all
less RBC ans usions, and da a has no been censo ed o
ans usions.
Figu e 1 e lec s he e olu ion o hemoglobin le els in
bo h g oups a he ou s udy-de ined ime poin s.
Despi e he lowe le els o hemoglobin a diagnosis o
he FCM g oup (9.6±1.4 s. 10.0±1.2 g/dL, p<0.005),
and much lowe RBC ans usion a e, signi ican ly
highe hemoglobin concen a ions we e achie ed by he
FCM g oup a hospi al admission, discha ge, and 30 days
pos -su ge y (Table 3;Fig.1). Mean o al hemoglobin
inc eases signi ican ly a o he FCM g oup be ween di-
agnosis and hospi al admission (1.5 s. 0.5 g/dL;
p<0.0001) and be ween diagnosis and 30 days pos -
su ge y(3.1 s.1.5g/dL;p<0.0001). This was also he
case when doing he analysis o ans used and non-
ans used pa ien s: mean o al hemoglobin inc ease be-
ween diagnosis and 30 days pos -su ge yin ans used
pa ien s was 3.5±1.9 FCM s. 1.4±1.6 no-IV (p<0.05)
and in non- ans used pa ien s was 3.1±1.9 FCM s. 1. 6
±1.8 no-IV (p<0.001).
A simila pe cen age o pa ien s wi h Hb≤10 g/dL was
obse ed a diagnosis (79 %) in bo h g oups. This a e
descends by nea ly 20 % o he no-IV g oup and 30 %
in he FCM g oup a ime o hospi al admission. The
pe cen age o pa ien s wi h Hb≤10 g/dL was signi ican -
ly lowe in he FCM g oup a hospi al discha ge (61.6 %
FCM s. 75.7 % no-IV i on, p<0.05)anda 30days
pos -su ge y (12.0 % FCM g oup s. 28.9 % no-IV i on,
p<0.05). Fu he mo e, he pe cen age o pa ien s wi h
no malized hemoglobin a 30 days pos -su ge y was sig-
ni ican ly highe in he FCM g oup s. no-IV i on (40.0
s. 26.7 %, p<0.05).
Figu e 1also shows he e olu ion o se um e i in
le els. A 30 days a e -su ge y, he a e age FCM-
ea ed pa ien p esen ed no ecognizable signs o i on
de iciency anemia (being he mean o Hb: 12.6 g/dL
[≥12 g/dL]; se um e i in: 218 ng/mL [≥30 ng/mL]; and
sa u a ion ans e in index: 25.1 % [≥20 %]) compa ed
wi h he no-IV g oup ha did no each no malized mean
alues (Table 3).
Figu e 2illus a es how he pe cen age o hemoglobin e-
sponde s (Hb inc ease o ≥1.5 g/dL) signi ican ly inc eased in
he g oup ea ed wi h FCM compa ed o he no-IV g oup:
Table 2 Need o allogenic RBC
ans usion (pe cen age o
pa ien s) and mean RBC uni s
ans used
No-IV i on FCM p
Need o RBC ans usion (o e all), % 38.7 9.9 <0.001
Need o RBC ans usions (pe i-su ge y pe iod), % 31.8 8.3 <0.001
Need o RBC ans usion (pos -su ge y un il day 30), % 16.7 5.0 0.005
Need o RBC ans usion (by su ge y), %
Open su ge y, % 37.7 17.1 <0.05
Lapa oscopic, % 25.4 0.0 <0.0001
Mean uni s o RBC ans used (o e all) 0.8 0.2 <0.0001
Mean uni s o RBC ans used (pe i-su ge y) 0.5 0.1 <0.0001
Mean uni s o RBC ans used (pos -su ge y un il day 30) 0.3 0.1 <0.05
Mean uni s o RBC ans used (by su ge y)
Open su ge y 1.0 0.4 <0.01
Lapa oscopic 0.6 0.0 <0.0001
FCM e ic ca boxymal ose, RBC ed blood cell
546 In J Colo ec al Dis (2016) 31:543–551
48.1 s. 20.0 % be ween diagnosis and hospi al admission
(p<0.0001) and 80.0 s. 48.9 % be ween diagnosis and
30 days a e su ge y (p<0.0001).
Pos -su ge y complica ions
A nume ically lowe o al numbe o ein e en ions and
complica ions ela ed o su ge y (including su u e dehis-
cence, pa aly ic ileus, hemope i oneum, ec al bleeding,
h omboembolism, e c.) a 30 days a e su ge y we e
seen in he FCM g oup in compa ison wi h no-IV pa-
ien s: 20.7 s. 26.5 % (OR=1.4; 95 % CI: 0.8–2.4; p=
0.311) (Table 4).
Impac on hospi al s ay
The leng h o hospi al s ay, measu ed om he day o
su ge y un il he day o discha ge, is shown in Fig. 3.
Table 3 Mean (±SD)
hemoglobin, hema oc i , MCV,
and i on pa ame e s a di e en
ime poin s be o e and a e
su ge y. G oups we e no
censo ed o ans usions
Hb
(g/dL)
Hema oc i
(%)
s-Fe i in
(ng/mL)
T-SAT index
(%)
MCV
(10
−15
L)
Diagnosis
No-IV i on 10.0±1.2 31.8±3.4 20.0±20.8 7.6±4.9 78.4±8.6
FCM 9.6±1.4** 31.1±3.9 39.6±62.9 8.0±5.9 79.3±8.2**
Hospi al admission
No-IV i on 10.5±1.3 33.1±3.9 24.0±21.6 7.9±3.1 80.6±7.9
FCM 11.0±1.7* 34.9±5.0* 296.6±292.1*** 19.1±11.6*** 84.5±7.3***
Hospi al discha ge
No-IV i on 10.3±1.2 32.1±3.5 305.0±323.6 16.9±15.4 82.6±6.9
FCM 10.7±1.4* 33.4±4.4* 298.1±294.5 18.2±10.5 86.4±6.6***
30 days pos -su ge y
No-IV i on 11.6±1.3 36.4±5.9 102.1±210.1 15.9±13.3 83.0±7.4
FCM 12.6±1.3*** 38.8±3.7*** 218.1±218.3* 25.1±18.2* 88.6±5.3***
FCM e ic ca boxymal ose, s- e i in se um e i in, T-SAT ans e in sa u a ion index (%), MCV mean co pus-
cula olume (10
−15
L)
*no-IV i on s. FCM, p<0.05; **no-IV i on s. FCM, p<0.005; ***no-IV i on s. FCM, p<0.001
20 24
305
102
40
297 298
218
10.0
10.5
10.3
11.6
9.6
11.0
10.7
12.6
0
50
100
150
200
250
300
350
08
09
10
11
12
13
Diagnosis Hospi al admission Hospi al discha ge 30 days pos -su ge y
Se um Fe in (ng/mL)
Hemoglobin (g/dL)
No IV i on (Fe in) FCM (Fe in) No IV i on (Hb) FCM (Hb)
**
*
*
***
‡
†
Fig. 1 E olu ion o hemoglobin
le els (g/dL) a ou ime poin s:
diagnosis, hospi al admission,
discha ge, and 30 days pos -
su ge y. G oups we e no
censo ed o ans usions.
Signi ican di e ences be ween
g oups a e ma ked wi h an
as e isk o Hb and dagge o
se um e i in (*p<0.05; **
/
†
p<0.005; ***
/‡
p<0.001). Fe ic
ca boxymal ose (FCM)was
adminis e ed du ing diagnosis
pe iod
In J Colo ec al Dis (2016) 31:543–551 547

The FCM g oup had a signi ican ly sho e mean leng h
o hospi al s ay: 8.4±6.8 days compa ed o he no-IV
i on g oup (10.9±12.4 days) (p<0.001). O e all, pa ien s
ha equi ed RBC ans usion had a longe hospi al s ay
han pa ien s wi hou ans usion (FCM 9.2±9.4 days s.
no-IV i on 12.0±13.0 days; p<0.005).
Sa e y o e ic ca boxymal ose
F om he FCM- ea ed pa ien s, no dea hs, hype sensi i -
i y, o o he se ious ad e se d ug eac ions we e
obse ed.
Discussion
P eope a i e anemia in pa ien s wi h su gical bleeding
isk associa ed wi h colo ec al cance has p o ed e y
p e alen and is an independen isk ac o o he e-
qui emen s o allogeneic RBC ans usion [12]. Unde
his global pe spec i e, and conside ing he lack o con-
olled s udies wi h a signi ican numbe o pa ien s, ou
p ospec i ely de ined and ea ed popula ion demons a -
ed a signi ican clinical bene i o he p eope a i e ad-
minis a ion o an IV i on supplemen a ion using e ic
ca boxymal ose (FCM) when compa ed o a e ospec i e
20.0
49.0
48.1
80.0
00
10
20
30
40
50
60
70
80
90
Admission 30 days pos -su ge y
% Responde s
(Hb inc ease ≥1.5g/dL)
No IV i on
FCM *
*
Fig. 2 Pe cen age o hemoglobin
esponde s—de ined as hose
wi h an Hb inc ease o ≥1.5 g/
dL—a hospi al admission and
30 days pos -su ge y wi h espec
o Hb diagnosis le els. Da a was
no censo ed o ans usions
Table 4 Incidence o pos -
su ge y complica ions No-IV i on
(n=155)
FCM
(n=111)
p
To al numbe o complica ions ( om su ge y un il 30 days pos -
su ge y) (% pa ien s)
25.5 22.5 NS
In ec ion 48.6 56.5
Su u e ailu e 32.4 21.7
Pa aly ic ileus 24.3 17.4
Rec o hagia 16.2 8.7
Hemope i oneum 10.8 4.3
Th omboembolic complica ion 10.8 0.0
Su gical ein e en ion (% pa ien s) 13.4 6.7 NS
Hospi al eadmission (su gical- ela ed cause) (% pa ien s) 3.9 4.0 NS
FCM e ic ca boxymal ose, NS non-signi ican
548 In J Colo ec al Dis (2016) 31:543–551
coho (wi h simila baseline cha ac e is ics). This o e all
ou old educ ion o ans usions (and hence associa ed
isk ac o s) was achie ed using FCM which was well
ole a ed in his g oup o pa ien s and demons a ed a
a o able bene i - isk p o ile. Fu he mo e, he obse ed
needs o ans usion we e i e imes (p e-and
in aope a i e) and almos h ee imes highe
(pos ope a i e) o he g oup ha had no ecei ed IV
i on. In e es ingly, he pa ien s in his coho we e all
ecei ing o al i on supplemen a ion a ime o diagnosis.
Simila dec eases in ans usion equi emen s o FCM-
ea ed pa ien s ha e been epo ed in a s udy ha compa es
he p e-ope a i e adminis a ion o FCM wi h he IV i on su-
c ose adminis a ion in a small coho o 45 pa ien s ea ed o
anemia in colon cance esec ion [18]. In his s udy, Bisbe and
collabo a o s obse ed a no iceable educ ion in he pe cen -
age o pa ien s ha equi ed RBC ans usion in he FCM
g oup ( om 40 % wi h i on suc ose o 7 % wi h FCM), as
well as ewe i on adminis a ion sessions (as FCM may be
adminis e ed a a single dose o 1000 mg i on pe session s.
only 200 mg o i on suc ose). Analogously, simila ends in
educing allogenic RBC ans usion equi emen s we e ob-
se ed wi h FCM in a h ee-coho e ospec i e s udy ha
included a o al numbe o 154 pa ien s wi h GI cance sub-
mi ed o lapa oscopic esec ion (gas ec omy, igh o le
colec omy, o ec um esec ion) [23]. E en hough ini ial
le els o Hb we e highe in he non-anemic g oup o pa ien s,
he anemic FCM g oup equi ed simila mean RBC uni s
ans used, and bo h we e signi ican ly lowe (p<0.001) han
in he anemic no-IV- ea ed g oup (0.5, 0.4, and 2.4,
espec i ely).
In con as , a p e ious andomized placebo-con ol
clinical ial (n=60) did no ind suppo o he use o
in a enous i on suc ose (600 mg i on in wo di ided
doses, 14 days be o e su ge y) as a p eope a i e supple-
men a ion o educe he likelihood o allogenic RBC
ans usion o pa ien s unde going esec ional su ge y
o colo ec al cance (19.2 % placebo s. 5.9 % in i on
suc ose; p=0.335) [24]. Howe e , al hough no eaching
s a is ical signi icance, he numbe o ans usions was
s ill nume ically highe in he placebo g oup, and i
migh be hypo hesized ha he adminis e ed i on doses
we e no su icien o mee he i on de ici in hese
pa ien s.
Wi hin ou s udy, and e en despi e signi ican ly ewe pa-
ien s ans used, a 1 mon h pos -su ge y, as o e all, he
FCM- ea ed pa ien s did no e lec signs o anemia, as well
as no signs o i on de iciency (mean e i in and ans e in
sa u a ion index we e a no mal alues). Ou da a in a la ge
pa ien g oup ex ends o he 30-day pos -su ge y pe iod he
p e iously ound e idence o imp o ed hemoglobin concen-
a ions and educed ans usions in gas oin es inal cance
pa ien s wi h anemia ea ed wi h FCM [23]. Mo eo e , in
hose anemicpa ien sincluded in ou s udy who ha e ecei ed
FCM, almos one ou o wo eached no malized hemoglobin
le els a e 1 mon h om he colon cance esec ion and de-
spi e hei lowe mean hemoglobin le els a diagnosis and
hei lowe a e o ans usion equi emen , while in pa ien s
wi h no-IV i on adminis a ion, his pe cen age was only
a ound 26 %. Ou da a u he suppo s he p eope a i e ea -
men wi h e ic ca boxymal ose in anemic colon cance pa-
ien s who a e planned o su ge y, wi h bene i s ex ending
un il 30 days pos -su ge y.
In addi ion o he educ ion in ans usion equi e-
men s and he imp o ed i on pa ame e s, ou s udy dem-
ons a es o he i s ime he bene i o a p eope a i e
FCM adminis a ion s a egy in he pe i- and pos -
su ge y pe iods when ea ing his kind o pa ien s.
Speci ically, impo ance should be gi en o he obse ed
ela ion o he mean hospi al leng h o s ay which was
signi ican ly educed wi h he FCM adminis a ion by a
mean o al o 2.5 days. Likewise, he pos ope a i e ben-
e i s o in a enous i on adminis e ed p e iously o he
su ge y ha e been epo ed ecen ly in o he pa ien p o-
iles, i.e., hose submi ed o non-ca diac su ge y, gyne-
cological umo esec ion, ca diac al e eplacemen , and
o hopedic p ocedu es in e ms o educ ion o pos -
su ge y complica ions and educed hospi al leng h o s ay
[10,16,19,20,25]. Finally, i has uled ou any link
be ween he su gical app oach and possible di e ences
be ween g oups wi h ega d o complica ions in he 30-
day pos -su ge y pe iod.
As a esul o hese imp o emen s, p e ea men wi h FCM
in anemic colon cance pa ien s seems o be a cos -e ec i e
in e en ion. The inc emen al cos s o IV i on ea men a e
e y likely o be o se by he cos sa ings due o educ ions in
10.9
8.4
0
2
4
6
8
10
12
Hospi al s ay
Time (days)
No IV i on
FCM
p<0.001
Fig. 3 Mean leng h o hospi al s ay measu ed om he day o su ge y
un il he hospi al discha ge
In J Colo ec al Dis (2016) 31:543–551 549
leng h o s ay and ans usion a es. The ex en o his eco-
nomic ad an age will be assessedin a u he wi hin- ial anal-
ysis. In a p e ious Spanish cos analysis aking in o accoun
bo h d ug acquisi ion cos s o FCM and i on suc ose as well as
adminis a ion cos s in anemic pa ien s unde going majo
elec i e su ge y, he inal cos bene i o FCM adminis a ion
pe ea men compa ed wi h he common IV i on suc ose
he apy was demons a ed by p o iding a mean o €63 sa ings
pe pa ien FCM ea men [18].
As s eng hs o ou s udy, i should be men ioned he num-
be o pa ien s conside ed o he analysis in he p ede ined
g oups as well as hei homogenous baseline and clinical cha -
ac e is ics in bo h g oups. I is also impo an o highligh ha
he signi ican ends obse ed in he measu ed ou comes we e
achie ed a e simila labo a o y alues a diagnosis and su -
gical cha ac e is ics in bo h g oups, al hough he FCM g oup
showed a sligh ly educed hemoglobin a baseline. The p es-
en s udy has se e al limi a ions ha wa an acknowledg-
men . Speci ically, he non- andomized design limi s he in-
e p e a ion o he esul s. Howe e , hese pa ien s ep esen
“ eal-li e”clinical p ac ice, and hence, his is also a s eng h o
his esea ch. Fu u e andomized con olled ial(s) ocused on
he use o FCM ea men in p eope a i e anemic colo ec al
cance pa ien s s. a simila ac i e supplemen may aid o
con i m ou indings.
In conclusion, ou da a demons a e ha p eope a i e e ic
ca boxymal ose ea men in i on-de icien colon cance pa-
ien s wi h anemia signi ican ly educed he leng h o hospi-
aliza ion, dec eased bo h he pe iope a i e and pos ope a i e
allogenic RBC ans usion equi emen s, showed no signs o
i on de iciency anemia a 30 days pos -su ge y, and was sa e
and well ole a ed. Based on educ ion o RBC ans usions
and leng h o hospi al s ay, i can be assumed ha he p eop-
e a i e adminis a ion o e ic ca boxymal ose in i on-
de icien colon cance pa ien s wi h anemia unde going su -
ge y could esul in signi ican cos sa ings.
Acknowledgmen s The au ho s hank Emili González-Pé ez om he
Medical W i ing Depa men a TFS De elop (Spain) o his aluable
w i ing assis ance and Raquel A cones om he Hospi al Pue a de Hie o
(Mad id) o he collabo a ion in he acquisi ion o da a.
Compliance wi h e hical s anda ds
Disclaime Pa ial esul s o he p esen s udy we e p esen ed a he
Diges i e Disease Week 2013 held in O lando, FL (USA), and a he
16 h Annual Mee ing o he Spanish Associa ion o Gas oen e ology
(AEG)2013heldinMad id(Spain).
Funding The p esen wo k was unded by Vi o Pha ma España SL.
Medical w i ing suppo was p o ided by TFS De elop and was unded
by Vi o Pha ma España SL.
Con lic o in e es Me cedes Cucala is an employee o Vi o Pha ma
España. The o he au ho s decla e no con lic o in e es .
E hical app o al All p ocedu es pe o med in s udies in ol ing hu-
man pa icipan s we e in acco dance wi h he e hical s anda ds o he
ins i u ional and/o na ional esea ch commi ee and wi h he 1964
Helsinki decla a ion and i s la e amendmen s o compa able e hical s an-
da ds (2013 Fo aleza).
In o med consen In o med consen was ob ained om all indi idual
pa icipan s included in he s udy.
Open Access This a icle is dis ibu ed unde he e ms o he C ea i e
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