Ferric carboxymaltose reduces transfusions and hospital stay in patients with colon cancer and anemia

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 Commons A ibu ion 4.0 In e na ional License (h p:// c ea i ecommons.o g/licenses/by/4.0/), which pe mi s un es ic ed use, dis ibu ion, and ep oduc ion in any medium, p o ided you gi e app o- p ia e c edi o he o iginal au ho (s) and he sou ce, p o ide a link o he C ea i e Commons license, and indica e i changes we e made. Re e ences 1. Shande A, Knigh K, Thu e R e al (2004) P e alence and ou - comes o anemia in su ge y: a sys ema ic e iew o he li e a u e. Am J Med 116(Suppl 7A):58S–69S. doi:10.1016/j.amjmed.2003. 12.013 2. 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