ebook img

4th Mediterranean Multidisciplinary Course on Iron Anemia April 29th–30th 2016, Madrid, Spain PDF

43 Pages·2016·4.13 MB·English
Save to my drive
Quick download
Download
Most books are stored in the elastic cloud where traffic is expensive. For this reason, we have a limit on daily download.

Preview 4th Mediterranean Multidisciplinary Course on Iron Anemia April 29th–30th 2016, Madrid, Spain

Expert Review of Hematology ISSN: 1747-4086 (Print) 1747-4094 (Online) Journal homepage: http://www.tandfonline.com/loi/ierr20 th 4 Mediterranean Multidisciplinary Course on Iron th th Anemia April 29 –30 2016, Madrid, Spain Sandro Barni th To cite this article: Sandro Barni (2016) 4 Mediterranean Multidisciplinary Course on Iron th th Anemia April 29 –30 2016, Madrid, Spain, Expert Review of Hematology, 9:sup1, 1-42, DOI: 10.1080/17474086.2016.1217153 To link to this article: http://dx.doi.org/10.1080/17474086.2016.1217153 Published online: 12 Sep 2016. Submit your article to this journal Article views: 164 View related articles View Crossmark data Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ierr20 Download by: [5.89.74.77] Date: 20 September 2016, At: 01:49 EXPERTREVIEWOFHEMATOLOGY,2016 VOL.9,NO.S1,1–42 http://dx.doi.org/10.1080/17474086.2016.1217153 ABSTRACT BOOK 4th Mediterranean Multidisciplinary Course on Iron Anemia April 29th–30th 2016, Madrid, Spain Back to the future: a new iron era thisneworalironformulationforthedenovouserorforthose shifting from other types of iron salts. Sandro Barni The metabolism of iron in cancer patients was well depicted by Paolo Pedrazzoli, who described iron parameters OncologyDepartment,MedicalOncologyUnit,ASSTBergamo Ovest, in oncology, a condition where increased iron storage and Treviglio,Italy reduced iron saturation determine the so-called functional anemia. A new frontier of iron anemia in cancer patients is Edited by Dr Sandro Barni, Director of Oncology Department, due to the use of molecular agents, targeting specific path- MedicalOncologyUnit,ASSTBergamoOvestTreviglio(BG).The waysandcriticalfortumorgrowth.Someofthesetargets(e.g. presentsupplementhasbeenpreparedincollaborationwithDr. cKIT, flt-3, and mTOR) can influence erythropoiesis in cancer GermanoTarantino,ScientificDirector,PharmanutraSpA. patients leading to frequent cases of low-moderate grades of Anemiaisaveryfrequentsymptomassociatedwithahigh anemia during treatment. The management of such type of number of diseases as the most frequent laboratoristic sign, anemia is controversial because erythropoiesis-stimulating complicating them as a side effect. agents are not labeled for this indication. Fausto Petrelli has Inonco-hematology,anemiaplaysapivotalroleinaltering presented new literature data reviewing the frequency of the quality of life, since it is one of the principal components anemia with targeted therapy in more than 90 clinical trials. of fatigue, andindelaying or interfering with oncologictreat- The experience with Sucrosomial® Iron in preexisting low- ments, worsening clinical course and prognosis. grade anemia before the start of chemotherapy is surprising Thisyear,wehavepointedoutourattentionontheuseof and intriguing. Will it be the way we will manage these cases preemptiveirontoavoidfutiletransfusions,ontheuseofiron of anemia with new oncologic drugs? Finally, Giulio Giordano in all internal medicine branches disease (e.g. gastroenterol- presented a randomized study comparing high dose of ogy), and on the approach to iron supplementations in hard- Sucrosomial® Iron to IV iron in hematologic patients. Last, to-treat forms of anemia such as anemia due to molecular butnotleast,GarciaErceexplainedhowatransfusion-sparing agents used in oncology, and functional anemia due to protocolcouldbeimplementedinourcountriesfromatrans- chronic disease, best depicted by cancer-related anemia. fusional service point of view. Saving blood means saving Sucrosomial® Iron represents a relatively new but still lives, costs, and toxicity of allogeneic blood transfusions. uniquepreparationofferricpyrophosphateconveyedthrough The magisterial lecture, held by Mercè Cladellas, has under- a phospholipid and sucrose esters of fatty acids matrix, that lined the negative effects of anemia in cardiology and cardiac appears useful in all that conditions associated with chronic surgery and how the cardiology field could benefit from an inflammation or iron deficiency in, and not only, onco-hema- effectiveironsupplementationintermsofprognosis,outcome, tology diseases. Gastroenterology and nephrology specialists, andqualityoflife.Duetotheemergingimportanceofacorrect for example, can now benefit from this new formulation, and iron supplementation in cardiac patient, this aspect should be onco-hematologists can safely replace older iron tablets, studiedfurtherandincludedinthenextIronAnemiaCourse. usually associated with bothersome gastrointestinal adverse The new frontiers of treating anemia in internal medicine events,withSucrosomial®Iron,withsimilarefficacyofIViron, deserve today an appropriate international audience, well per- potentially associated with acute side effects and ambulatory formed in this 4th Mediterranean Multidisciplinary Course on rooms accesses. Iron Anemia held in Madrid on 29th and 30th April 2016, of Someexpertsininternalmedicine,hematology,andoncol- which we report official congressional acts. The 4th ogy subspecialties have discussed important setting where Mediterranean Multidisciplinary Course on Iron Anemia repre- Sucrosomial® Iron could be widespread used. A preclinical sented a significant opportunity to share different opinions and model of pharmacokinetic and liver toxicity of Sucrosomial® to convey various clinical experiences, mainly about the recent Iron was presented by Italian scientists. Celiac disease, a evidencesonSucrosomial®Ironintreatingirondeficiencyanemia. chronic condition with reduced iron absorption, and bariatric At the end of the course, I hope, we have added some surgery, a branch of abdominal surgery specialties, represent morepiecesofinformationtotheknowledgelearnedfromthe new platforms where Sucrosomial® Iron could be implemen- lastAnemiaCourseheldinRomein2015.Newlessonslearned ted. Inflammatory bowel diseases are further chronic condi- today in Madrid are still of paramount importance. We can tions where anemia of inflammation is the rule. Guillermo now, likely, appreciate a new product, such as Sucrosomial® Bastida showed us the role of Sucrosomial® Iron in patients Iron, for managing hard-to-treat cases of chronically ill intolerant to other oral iron formulation. Ideally, this means patients who require a treatment for anemia and that would that all branches of internal medicine could be the arena for mean treating their fatigue, anorexia, mood depression, ©2016InformaUKLimited,tradingasTaylor&FrancisGroup 2 ABSTRACTS malaise, which are all signs of an impaired quality of life. We reason, the organism has developed an efficient transport havelearnedsomenewinsightsaboutsomecausesofanemia system [2]. The first barrier iron encounters is the apical and, in particular, we would like to thank Antonello membrane of the duodenal enterocyte that is a specialized Pietrangelo for the magisterial lecture he offered in the audi- absorbent cell of the intestinal epithelium involved in the torium. Finally, I hope this meeting will teach us that taking iron transport. Iron is initially solubilized through reduction care of (preemptive) management of anemia with iron pro- of Fe3+ to Fe2+. This is then carried to the cell interior by a ducts will reduce the chance for our patients to receive futile transport process mediated by the carrier DMT1. transfusions, potentially dangerous for most subjects, so Subsequently, iron is transferred to the basolateral side of expensive in terms of resource consuming, cost, and side the enterocyte, where it may either be stored via binding to effects. ferritin or cross the membrane and reach the systemic circu- lation. Quite hypothetically another type of Fe3+ transport across the intestinal epithelium could involve the cellular Funding endocytosis of a Fe3+ carrier, e.g. nano- or microparticulate. The 4th Mediterranean Multidisciplinary Course on Iron Anemia is sup- From here, the importance is understood of the pharmaceu- portedbyanunrestrictededucationalgrantfromPharmanutraSpA,Italy tical formulation which should directly carry the ferric ion in andZambonS.A.U.,SpainandPortugal. the intestine and promote its absorption. The formulation should not release the Fe3+ before reaching the general circulation that is the site of action. Therefore, to evaluate Declaration of interest the ability of the carrier to transport Fe3+ across SBarniandGTarantinohavenorelevantaffiliationsorfinancialinvolvement the epithelium, an ex vivo model based on excised rat intes- withanyorganizationorentitywithafinancialinterestinorfinancialconflict tine could be more predictive. The present work compares with the subject matter or materials discussed in the manuscript. This the data obtained by the two models, namely that based on includesemployment,consultancies,honoraria,stockownershiporoptions, experttestimony,grantsorpatentsreceivedorpending,orroyalties. theCaco-2cellsmonolayerandthatbasedontheexcisedrat intestine,tounderstandthemechanismofthepermeationof ironandtocomparethebioavailabilityoftheinnovativeoral ABSTRACTS ironformulationbasedonSucrosomial®Iron(SiderAL®)with different iron formulations. In vitro and ex vivo models to study Sucrosomial® Iron pharmacokinetics Methods Ylenia Zambito To determine iron uptake by Caco-2 cell monolayer, a pre- DepartmentofPharmacy,UniversityofPisa,Pisa,Italy viously reported method was used [1]. Tested samples are listed in Table 1. Introduction Eachsamplecontainedadifferentquantityofiron;therefore,in ordertomakehomogeneouscomparisonbetweenformulations, Iron deficiency is one of the most widespread nutritional defi- ineachexperimentanequivalentdoseof200µgofironwasused. ciencies. Oral therapy for iron deficiency is mainly based on TheexperimentalprotocolusedisshowninFigure1.Briefly,Caco- immediate-release formulations of ferrous iron. To overcome 2cellswereseededatadensityof105cells/wellin12-wellplates, gastrointestinal epithelial barriers, there is a need for new maintained in cell culture medium and used in the iron uptake absorption enhancers. Recent data indicate that sucrose esters experiments at 14 days post-seeding. Immediately before the can enhance drug permeability through both transcellular and intestinal digestion period, the growth medium was removed paracellularroutes.Severalinvitroandexvivosystemshavebeen andasterilizedinsertringwasinsertedcreatingthetwo-chamber proposed to assess iron bioavailability. In order to understand system.A1.5-mLaliquotoftheintestinaldigestwaspipettedinto Sucrosomial® Iron absorption mechanism, we have performed theupperchamberandtheinsertringanddigestwereremoved. absorption study using Caco-2 cell model and a permeation After 24-h incubation, cells were harvested for analysis. Each studyusingexvivomodel. treatmentwasperformedinduplicateforeachreplicationofthe In fact, an experimental protocol that conjugates the experiment.Caco-2cellferritincontentwasmeasuredthroughan simulation techniques of the gastrointestinal digestion with enzyme-linked immunosorbent assay (ELISA) kit (USCN Life the iron internalizing phase by the Caco-2 cells has been set Science,USA)followingthemanufacturer’sinstructions. up [1]. Such a protocol appears very useful and predictive of the invivobehaviorsofar,asittakesintoaccountthe phase Table1.Samplestested. ofFe3+dissolutioninthegastrointestineandthesubsequent Sample Formulation Composition permeationacrosstheepithelium.Indeed,itcannotbetaken 1 Ferroussulfate(FS) Ironsalt for granted that the latter phase is slower than the former 2 LowphospholipidsSideral Ironpyrophosphate,lecithinlower and hence that it is the rate-determining one. It is known R.M.prototype(SLP) phospholipidconcentration, thatatpHvalueshigherthan3,theFe3+iontendstoformFe sucrester 3 SIDERALR.M.(SRM) Ironpyrophosphate,lecithin,sucrester (OH) , the water solubility of which is practically null. In fact, 3 4 SucresterSideralR.M. Ironpyrophosphate,lecithin,higher the Fe3+ bioavailability is very poor just because of its poor prototype(SRMS) sucresterconcentration solubility at the physiologic pH of the intestine. For this 5 Sunactive®(SUN),Taiyo Ironpyrophosphate,lecithin EXPERTREVIEWOFHEMATOLOGY 3 Figure2.Caco-2cellferritinformationasmeasured24hafterthestartofthe intestinal digestion period. *p<0.001, as compared to FS (one-way ANOVA followedbyDunnett’smultiplecomparisontest). number,tothoseofthehumanjejunum.ThesampleSRMshowed ahighereffectivenessinenhancingFe3+permeabilityacrossthe excisedratintestinethansamplesSLP,SRMS,andSUN. Conclusions ThedatadescribedinthisworkshowsthatSucrosomial®Iron Figure1.Experimentalprotocoloncellculture. formulation promotes Sucrosomial® Iron absorption across the intestinal epithelium. For permeation studies, the intestinal mucosa was excised from non-fasting male Wistar rats weighing 250–300 g. Rats References were killed and the first 20 cm of jejunum was immediately 1.Glahn RP, Lee OA, Yeung A, et al. Caco-2 cell ferritin formation removed.Theexcisedintestinewascutintostripsof1.5cm,rinsed predictsnonradiolabeledfoodironavailabilityinaninvitrodiges- freeofluminalcontents,andmountedinUssing-typechambers tion/Caco-2cellculturemodel.JNutr.1998;128:1555–1561. (0.78cm2exposedsurfacearea)withoutstrippingofftheunder- 2.Srai SK, Bomford A, McArdle HJ. Iron transport across cell mem- lying muscle layer. One milliliter of phosphate buffer pH 6.8, branes: molecular understanding of duodenal and placental iron uptake.BestPracResClinHaematol.2002;15:243–259. 0.13 M, made isotonic by the addition of sodium chloride (PBS 3.Shyla B,Bhaskar CV, Nagendrappa G. Iron(III) oxidized nucleophilic 6.8),wasaddedtotheapicalsideand3mLofaphosphatebuffer coupling of catechol with o-tolidine/p-toluidine followed by 1,10- solution pH 7.4, 0.13 M, isotonic (PB 7.4), was added to the phenanthrolineasnewandsensitivityimprovedspectrophotometric basolateralside(acceptormedium).Inordertoensureoxygena- methodsforironpresentinchemicals,pharmaceutical,ediblegreen tionandagitation,amixtureof95%O and5%CO wasbubbled leaves, nuts and lake water samples. Spectrochimica Acta Part A, 2 2 MolecularandBiomolecularSpectroscopy.2012;86:152–158. through each compartment. The Ussing chambers were then placedinawaterbathat37°C.Aftera20-minequilibrationperiod, themediumineachapicalcompartmentwasreplacedby1mLof Sucrosomial® Iron supplementation in anemic pre-thermostatedsampledispersion,(correspondingto200µgof patients with celiac disease not tolerating oral iron).TheapicaltobasolateraltransportofFe3+wasinvestigated. ferrous sulfate At 30-min intervals for a total of 240 min, 1 mL sample was Luca Elli withdrawn from the acceptor compartment and substituted with an equal amount of fresh pre-thermostated medium. The Center for the Prevention and Diagnosis of Coeliac Disease, permeated Fe3+ amount was determined by a previously GastroenterologyandEndoscopy, UnitFondazioneIRCCS Ca’ describedmethod[3]. GrandaOspedaleMaggiorePoliclinico,Milan,Italy Celiac disease (CD) is a common autoimmune disease of the smallbowel. Its presentation is extremely heterogenouswith Results and discussion a broad range of manifestations with variable severity ran- Data on iron uptake by the Caco-2 cell monolayer are shown ging from asymptomatic individuals to severe malnourish- in Figure 2, where it can be seen that Caco-2 cell monolayers ment or infertility [1]. The worldwide prevalence of CD is treated with SRM were able to significantly increase ferritin difficult to estimate and ranges from 1% to 3% of the expression about 7.4 times than those treated with ferrous general population in Europe and the USA [2–6]. CD may sulfate (FS) (Figure 2). present at any stage of the life; clinical pictures are defined Among various ex vivo intestinal epithelium models, the as: classical, particularly common among children, character- excisedratjejunummodelwaschosenforthepermeabilitystu- ized by malabsorption (diarrhea, statorrhea, lack of appetite, dies because its tight junctions are similar, in tightness and growth retardation, and deficiencies in fat soluble vitamins, 4 ABSTRACTS iron, calcium, and folic acid) and atypical, more common wasHblevels;secondaryoutcomeswerethelevelsofsympto- during adolescence and adulthood and presenting with matic VASs. laboratory abnormalities, irritable bowel syndrome, osteope- Nowadays, 34 treated CD patients have been enrolled (33 nia, fertility problems, and iron deficiency anemia (IDA) [7]. females,42±9yearsofage).Intotal,18(53%)subjectsreported Both genetic and environmental factors are involved in the previoussideeffectswithsulfateiron(allfemales,44±10yearsof development of CD. The disease is triggered and maintained age)andthusreceivedSucrosomial®Iron(Sideral®Forte30mg); in genetically susceptible individuals, by an immunological 16(1 male,41 ± 8yearsof age)were administeredwith sulfate responsefollowing the ingestionofwheatglutenandsimilar irontablets(ferrograd105 mg) oncea day for90 days.Patients alcohol soluble proteins (prolamines) [8,9]. All patients were followed after 45 and 90 days from the beginning of the express the human leukocyte antigen (HLA) type II DQ2 supplementation.Nostatisticaldifferenceswerepresentbetween and/or HLA-DQ8 haplotypes [12]. Gluten peptides, after thetwogroupsaboutdemographic,clinicalcharacteristics,smok- being deamidated by the transglutaminase 2 (TG2), bind inghabits,andnumberofusedtampons.Atenrolment,Hbwas HLA-DQ2 and HLA-DQ8. The consequent result is a destruc- 10 ± 1 g/dL, Ht 34% ± 3%, MCV 74 ± 5 fl, iron 46 ± 27 g/dL, tive intestinal CD4+ T cell response [8]. After their activation, transferrin saturation 11% ± 7%, ferritn 12 ± 14 ng/mL. Both the CD4+ T cells produce cytokines, which support an therapiesinducedastatisticallysignificantincreaseofHb12±1 inflammatory cascade with an intestinal inflammation. All and12.3±1inpatientsadministeredwithSucrosomial®Ironand this mechanism results in the alteration of the intestinal sulfate iron, respectively. No variation of VAS was evidenced mucosa, characterized by villous atrophy, crypt hyperplasia, between patients assuming sulfate of Sucrosomial® Iron. Only and infiltration of inflammatory cells [10]. CD is currently well-beingVASsignificantlyincreased,independentlybythetype diagnosed with IgA anti-tissue transglutaminase (tTG) serol- ofsupplementationfrom4±2to6±2. ogy tests, followed byconfirmatory biopsiesof the duodenal Among CD patients, 12 (33%) maintained villous atrophy bulb and second part classified by the Marsh classification in spite of strict GFD (Marsh 3a, 3b or 3c); 6 assumed sulfate [11]. CD frequently presents IDA, which usually reverts with iron and 6 sucrosimial iron. Also, in this case, both the a gluten-free diet (GFD). However, some patients present therapies significantly increased the Hb levels and other persistent IDA despite their clinical responsiveness to GFD. iron status parameter. Also, the levels of Hb after treatment The contributions of malabsorption, inflammation, or genet- did not differ between patients with or without duodenal ics to CD-associated IDA remain unclear, although response atrophy. to iron supplementation could be improved by the use of a In conclusion, the presented preliminary findings indicate tolerated iron or by the use of an iron formulation increas- that Sucrosomial® Iron is effective and well tolerated in CD ing the intestinal absorption [12]. patients with a previous failure of sulfate iron. Experimental section Sucrosomial Iron 30mg 14 Sucrosomial® Iron (Sideral® Forte), a preparation of ferric Sulfate Iron 105mg 13 pyrophosphate conveyed within a phospholipid membrane associated with ascorbic acid, is a new-generation oral iron 12 which shows a high gastrointestinal absorption and high b 11 bioavailability with a low incidence of side effects due to H lack of any direct contact with intestinal mucosa. In compar- 10 ison with the other standard oral iron preparations, 9 Sucrosomial® Iron seems to be a promising new strategy of 8 iron replacement in CD patients. The ongoing study treated T0 T45 T90 with Sucrosomial® Iron treated CD patients with IDA and a previous therapeuticfailure using sulfate iron tablets. It wasa Day prospective open study. All patients were following a strict GFD for at least 12 months with normalization of anti-trans- n 30 Sucrosomial Iron 30mg o glutaminase IgA. Moreover, consecutive enrolled patients ati 25 Sulfate Iron 105mg were previously investigated by means of duodenal histology ur at 20 to look for possible correlations with atrophy degrees (Marsh s n scale). Clinical and demographic data were recorded, and ri 15 r e symptomatic response to iron tablets was evaluated through sf 10 n 10-cm long visual analog scales (VASs). Evaluated symptoms a r were: diarrhoea, constipation, epigastric, and abdominal pain, T 5 stoolconsistencysatisfaction.AspecificVASevaluatedgeneral 0 well-being. Other causes of IDA were investigated when clini- T0 T45 T90 cally indicated. Associated vitamin or folic acid deficiencies Day were looked for and excluded. Primary outcome of the study EXPERTREVIEWOFHEMATOLOGY 5 References of childbearing age, require oral iron supplementation after the bariatric surgery. 1.BaiJC,FriedM,CorazzaGR,etal.Worldgastroenterologyorganisa- Additionally, a non-negligible percentage of women, who tion global guidelines on celiac disease. J Clin Gastroenterol. 2013;47:121–126. previouslyunderwentbariatricsurgery,requireparenteraliron 2.CatassiC,FabianiE,RatschIM,etal.ThecoeliaciceberginItaly.A therapysupplementationuntiltheestablishmentofthemeno- multicentreantigliadinantibodies screeningforcoeliacdisease in pause.Thisfactisdueinparttolowerpre-surgeryirondepos- school-agesubjects.ActaPaediatr.1996;412:29–35. itsinobesepatients,aphenomenonwhichalsotranslatesinto 3.CatassiC,KryszakD,BhattiB,etal.Naturalhistoryofceliacdisease agreatvariabilityinthetimeofoccurrenceofthedeficit(from autoimmunity in a USA cohort followed since 1974. Ann Med. 2010;42:530–538. months to years). Also, most of the obese women who 4.Catassi C, Ratsch IM, Fabiani E, et al. Coeliac disease in the year undergo bariatric surgery restore the menstrual period in 2000:exploringtheiceberg.Lancet.1994;343:200–203. almost 40% of the cases after a 4,6% weight loss. In many 5.FarrellRJ,KellyCP.Celiacsprue.NEnglJMed.2002;346:180–188. cases, despite taking high oral doses of conventional iron 6.Ferguson A. Coeliac disease research and clinical practice: main- supplementation, often causing gastrointestinal intolerance, taining momentum into the twenty-first century. Bailliere’s Clin Gastroenterol.1995;9:395–412. they fail to achieve optimal levels, requiring therefore chronic 7.Ludvigsson JF, Leffler DA, Bai JC, et al. The oslo definitions for parenteral therapy. coeliacdiseaseandrelatedterms.Gut.2013;62:43–52. In our series of patients (1100 patients who underwent 8.Schuppan D. Current concepts of celiac disease pathogenesis. bariatric surgery since the year 2000 until today), about 120 Gastroenterology.2000;119:234–242. womenofchildbearingage,requireparenteraltreatmentwith 9.Schuppan D, Junker Y, Barisani D. Celiac disease: from pathogen- esistonoveltherapies.Gastroenterology.2009;137:1912–1933. intravenous iron every 3 months, chronically, until the meno- 10.MarshMN.Thesmallintestine:mechanismsoflocalimmunityand pause is installed. The administration of intravenous iron, in glutensensitivity.ClinSci.1981;61:497–503. thedayhospital,takesbetween2and3hours,for2consecu- 11.Rubio-Tapia A, Hill ID, Kelly CP, et al., American College of tive days, every 3 months, which represents an important Gastroenterology. Acg clinical guidelines: diagnosis and manage- distortion of work and daily life of the patients. mentofceliacdisease.AmJGastroenterol.2013;108:656–676;quiz Sucrosomial® oral Iron may represent a treatment alterna- 677. 12.Zamani F, Mohamadnejad M, Shakeri R, et al. Gluten sensitive tive in these cases. Due to its new technology, based on the enteropathy in patients with iron deficiency anemia of unknown contactofsucrosomewithintestinalcellmembrane,the‘usual origin.WorldJGastroenterol.2008;14:7381–7385. mechanisms’ of intestinal absorption of the iron are not so important (such as gastric acid secretion, duodenum). Therefore, the bioavailability of Sucrosomial® Iron rises to 3.5 ResponsetoSucrosomial®oralIronsupplementation timescomparedwiththeconventionaliron.Sucrosomial®Iron in patients underwent bariatric surgery also has been proven to be effective and well tolerated, Andreea Ciudin comparedwithoralsupplementsofconventionalironinpreg- nancy,newborn,infant,chronickidneydisease,andinflamma- EndocrinologyandNutritionDepartment,Valld´HebronUniversity Hospital,Barcelona,Spain toryboweldisease.Thisformoforalironhasdemonstratedits effectiveness even against conventional iron in patients with intravenous therapy. Introduction To our knowledge, to date, there is no study using In the postoperative period, all the techniques of bariatric Sucrosomial® oral Iron in patients undergoing bariatric sur- surgeryinduceasignificantreductionintheintakeorabsorp- gery. In order to shed light on this issue, we have designed a tion of most of the nutrients. Therefore, bariatric surgery can single-center, open, prospective, interventional trial, including be associated with a risk of nutritional deficiency, which 40 women of childbearing age, who previously underwent increases over the years. One of the nutrients whose absorp- RYGB, and currently require chronic intravenous iron therapy. tion is affected in a significant way is iron, and the women of The subjects were divided into two parallel groups: 20 cases childbearing age are the most vulnerable. The daily recom- and20controlsmatchedbyage,previouslevelofhemoglobin mendation of iron intake in adults is 8 mg a day for men and (Hb),yearsaftersurgery,andpercentageofweightlost.The20 womenmorethan50years,and18mgperdayforwomenof cases were discontinued from the parenteral iron treatment age less than 50 years. The incidence of iron deficiency and and were treated with oral Sucrosomial® Iron 28mg/day for anemiaafterbariatricsurgeryisvariableaccordingtothetype three months. The 20 controls continued with 300mg iron ofsurgeryandthetimeafterthesurgery.Forinstance,aftera sucrose endovenously every 3 months. Total hemoglobin Roux-en-Y gastric bypass (RYGB), iron deficiency anemia is (Hb),ferritin, andtransferrin saturationindex(TSI)were deter- diagnosed between 10% and 40% of all the cases. Bariatric minedbeforeandafter3monthsoftreatmentinbothgroups, surgerytechniquesproducechangesofthedigestivetractand as well as tolerability. dietary habits that favor the iron deficiency. These changes are: (a) intolerance to red meat, leading to a decrease in the intake;(b)decreasedgastricacidsecretionbyresectionofthe Results proximal stomach, with the consequent relative deficit of parietal cells and iron absorption deficiency; (c) exclusion of NosignificantdifferenceswereseenbetweenthelevelsofHb theduodenum,whichisthemainplaceofmolecularironand (12.67 ± 1.06 g/dL vs 12.267 ± 1,35 g/dL, p = 0.081), ferritin hemeironabsorption.Mostofthepatients,especiallywomen (101.67 ng/dL vs. 88.89 nd/dL, p = 0.069), and TSI (24.11% vs. 6 ABSTRACTS 26.28%, p = 0.55) before and after the 3 months of treatment the patients is mixed, with an iron deficiency through contin- with Sucrosomial® Iron. We did not find any adverse effect uousgastrointestinallossesassociatedtotheanemiaofchronic during this period in the treatment group. Compared to the illnesses[6].Inaddition,wemustnotforgetthatthereareother control group, the final Hb levels were similar (Hb 12.267 ± causes of anemia such as the deficiency of vitamin B12 or of 1.35 g/dL and 12.1 ± 1.74 g/dL, respectively, p = 0.09). folic acid, malnutrition, the malabsorption or the ingesting of several medications (e.g. salazopyrine or thiopurines). The importance of anemia, even in non-anemic iron deficiency, Conclusion residesintheseriousdisruptionofqualityoflifethatitimplies. Actually, the presence of anemia can condition a disruption of Our study suggests that oral Sucrosomial® Iron might repre- quality oflifesimilar tothat ofadvancedcancerpatients [2]. sentan alternative therapyinpatients whorequire parenteral This is a very important aspect, since not long ago the treatment with iron after bariatric surgery. presence of anemia was only considered a marker of the Final remark: Sucrosomial® Iron might be an alternative activity of IBD, on occasion going unnoticed, in such a way treatmentinpatientswithsevereirondeficiencyafterbariatric that it was assumed that a certain anemia represented a surgery, which currently requires parenteral iron therapy due normal discoveryinIBDpatients and, assuch,did notrequire to intolerance to existing oral products or therapeutic failure. treatment. Now, it is well known that iron deficiency anemia Atthesametime,itmighthelptoreducehealthcarecostsand shouldbetreatedwithironassoonasitisdetected.Likewise, improve the quality of life of these patients. the therapeutic objective of the treatment should be to com- pletely cure the anemia and the iron deficiency, and not only to partially raise the hemoglobin or ferritin numbers. Efficacy and tolerability of Sucrosomial® Iron The treatment of the anemia should be started once the supplementationinIBD patientswith irondeficiency cause in known. In the case of treating an iron deficiency anemia and intolerance to iron oral salts anemia, iron should be administered at the same time as the Guillermo Bastida Paz medication to control the inflammation. UnidaddeEnfermedadInflamatoriaIntestinal,HospitalUniversitario Intravenous iron is very quick and efficient both for curing ypolitécnicoLaFe,Valencia,Spain anemia and for maintaining the iron deposits in IBD patients [6]. Because of its cost, and because of the need for it to be Anemia is the most frequent systemic complication in inflam- administered in a hospital, current guidelines [1] recommend matory bowel disease (IBD) [1–2], most of all in patients with the administration of intravenous formulas for those patients Crohn’s disease (CD) [3]. Its prevalence is quite variable in the in which hemoglobin numbers are lower than 10 g/dL, in different studies, according to its evaluation criteria and the thosewhotolerateironorallyorinthosewhorequireerythro- types of patients included [4,5]. A systematic review of the poiesis-stimulating agents [1]. The majority of the patients is literature describes prevalence of anemia in IBD of 16% in going to have mild anemia and will be treated with oral iron outpatients with IBD and of up to 70% in inpatients. If we [7].Oralironisanefficient,simple,cheap,andsafetreatment. take into account that the main cause of anemia is IBD itself, Theefficiencyoforalironvariesbetweendifferentstudies.For we understandthatthecauseofthe anemiainthe majorityof example,inastudycarriedoutinSpain,oralironmanagedto EXPERTREVIEWOFHEMATOLOGY 7 normalizehemoglobinnumbersinmorethan85%ofpatients. allwithpriorpoortolerationoforaliron.Ofthem,22(64.1%) In this study, oral iron was well tolerated, without assessing of the patients showed CD, 16 (73%) in remission at the theactivityofIBDandwithjust5%withdrawalthroughintol- beginningofthestudy.Intotal,17(35.9%)showedulcerative erance.Thepatientsthatdidnottolerateordidnotcuretheir colitis(UC),8(67%)wereinremission.Theaverageageofthe anemiawithoralironreceivedintravenousironwithexcellent patients was 42 years, the lower and upper limits were 21 results [7]. and 62 years. However, these excellent results were not reproduced in In total, 79.5% of the patients showed symptoms of iron all studies and undoubtedly oral iron presents clear and deficiency anemia. Asthenia was the most frequent symptom significant limitations [8]. One of its greatest limitations among the patients, present in all patients, followed by diffi- resides in the fact that a considerable percentage of IBD culty in concentrating and irritability in 48.4% and 45.2%, patients show poor tolerance to treatment with oral iron. In respectively. fact, on many occasions it can cause diarrhea, constipation, ThepatientsweretreatedwithadailydoseofSucrosomial® or abdominal pain, on the one hand hindering the perfor- Iron over 3 months. The majority of the patients (90.5%) per- mance (and with this real efficiency) and on the other it formed well. The tolerability of Sucrosomial® Iron, the primary can mislead us with an outbreak. In fact, a systematic objectiveofthestudyinthispopulationofpatientsintolerantto review describes that the appearance of secondary effects otheroralironformulaswasgood.Duringthestudy,thegeneral lead to the suspension of oral iron in up to 21% of patients well-beingofthepatientwasrecorded.Almostallpatients,100% with CD [4]. This percentage can reach a significant magni- and92%,hadagoodorslightlylowerthannormalopinionofthe tude, for example, Lugg et al. describe the failure of oral 4and12weeks,respectively.Additionally,thepercentageofthe iron in controlling anemia in two out of every three indivi- patients with gastrointestinal symptoms after taking the duals with IBD, due in part to the secondary effects, which Sucrosomial®Ironat4and12weeks(abdominalpain,constipa- appear in more than half of its patients [9]. These second- tion, loss of appetite, nausea, vomiting, change of color to the ary effects could be related to experimental data and sug- feces,orthepresenceofametallictaste)didnotincreaseover gest that the iron that is not absorbed could be toxic to themonitoring. intestinal mucous and even precipitate outbreaks of Althoughthepercentageoftheadverseeffectsgatheredwas IBD [10]. high (31 patients of 38 showed a total of 125 adverse occur- Forallofthesereasons,weunderstandthataneworaliron rencesoverthecourseofthestudy),two-thirdsofthem,66.4%, formula,withbettertolerability,wouldbeofgreatinterestdueto were of low intensity and only 6.4% were serious. The most thehigherfrequencyofanemiaandirondeficiency ofpatients frequent secondaryeffectswerea changein colorofthe feces withIDBaswellastheadverseeffectsassociatedtoclassiciron (63.2%),abdominalpain (44.7%),diarrhea(34.2%),constipation formulas with ferrous salts (ferrous sulfate, ferrous gluconate, (23.7%), and a metallic taste (21%), although only 42.7% were ferrous fumarate, and ferrous lactate). In this regard, a recent foundtorelatetothecase.Infact,in93.6%oftheoccurrences, formula,Sucrosomial®Iron,couldhavesomeadvantages.Thisis there was no change with regard to taking Sucrosomial® Iron, aSucrosomial®ferrouspyrophosphate,whichcontains30mgof 0.8%temporarilyinterruptedand5.6%permanently. ironthatiscoveredinsucrosoma.Thesucrosomaisformedbya In relation to the efficiency, one-third of the patients nor- liposome,asphericalstructureofaphospholipidicnaturesimilar malized the iron-deficient anemia data in 12 weeks. to those cell membranes of the human body, which are Hemoglobin values increased at 12 weeks from the average immersedinamatrixofsucroseestersoffattyacidsthatallow of11.1g/dLto11.8g/dL(p=0.0023)andthoseofferritinfrom it to cross the gastric acid barrier, reaching the small intestine 11.47 mcg/L to 13.1 mcg/L (Figure 1). unscathedandavoidingthepro-oxidanteffectofotherironsalts. The recovery of the data on iron deficiency was accompa- Once there, the sucrosoma and the iron that it contains are nied by an improvement in the questionnaires on quality of integrally absorbed through the intestinal M cells, without the life. The average rating in the questionnaire on quality of life needforspecifictransporters[11].TheMcells,duetotheirlow ofIBD(CCVVEII-9)improvedfrom61.2pointsto66.8pointson lysozymecontent,cantransportantigenswithalmostnoenzy- the final visit. The generic questionnaire on the quality of life, maticdegradationandallowtheirliberationwithoutmodifying theEuroQoL,improvedinalldimensions(mobility,dailyactiv- the lymphatic system. This differential absorption of the ities, pain/discomfort, and anxiety/depression) except in per- Sucrosomial® Iron gives it greater availability. Therefore, the sonal care (Figure 2). protectionofthesucrosomaavoidstheappearanceoftheclassic Therefore, Sucrosomial® Iron is well tolerated in patients secondaryeffectsofthetreatmentwithotherironsaltsallowing with IBD with prior intolerance to oral iron, and should be the microelement to overcome unscathed the gastric environ- considered as an alternative for the treatment of iron defi- ment to be directly absorbed into the intestine and directly ciency anemia in those patients who do not tolerate classic liberatedintotheliver[12]. prepared doses of oral iron. Anobservationalandmulticentricstudyiscurrentlybeing carried out to evaluate the tolerability of oral Sucrosomial® Iron (dietary supplement Fisiogen Ferro Forte®) in the colli- References sion of the iron deficit in patients with IBD previously intol- eranttothesaltsnormallyusedinoraliron.Theintermediate 1.Dignass AU, Gasche C, Bettenworth D, et al.; European Crohn’s analysis has been made with the data gathered until and Colitis Organisation [ECCO]. European consensus on September 2015. At this time, there were 39 valid patients, the diagnosis and management of iron deficiency and anemia 8 ABSTRACTS Figure1.Increaseinhemoglobin,ferritin,andISAT(%)levels SCOncologia,FondazioneIRCCSPoliclinicoS.Matteo,Pavia,Italy Anemia is common in cancer patients, and is associated with significant decrease in quality of life (QOL) and a negative impact on prognosis. The etiology of cancer-related anemia is multifactorial, but in most cases it is a consequence of the chronic disease process associated with malignancy. Alleviating anemia with erythropoiesis-stimulating agents (ESAs) improves energy, activity, and overall QOL, particularly among patients with mild-to-moderate anemia, and facilitate patientcopingwithactivetreatments.However,researchsug- gests that anemia is still under-recognized and undertreated. Figure2.Assessmentofthequalityoflifebeforeandafterthetreatment This may be partly due to the limitations of current ESA therapy, which includes a large percentage of patients who in inflammatory bowel diseases. J Crohns Colitis. 2015;9:211– do not respond to this treatment, the need for frequent dos- 222. ing,andtherelativelyslowtimetoresponse.Adequatepatient 2.GascheC.AnemiainIBD:theoverlookedvillain.InflammBowelDis. selection for treatment with ESA or other drugs/procedure is 2000;6:142–150. of pivotal importance in this setting. 3.Bergamaschi G, di Sabatino SA, Albertini A, et al. Prevalence and Dysregulations of iron metabolism causing iron deficiency pathogeneisofanemiaininflammatoryboweldisease.Influenceof anti-tumor necrosis factor-alpha treatment. Haematologica. represent a major cause of anemia of chronic diseases (ACDs). 2010;95:199–205. Also, data from the dialysis and cancer populations has clearly 4.Kulnigg S, Gasche C. Systematic review: managing anemia in shownthatanimportantfactorwhichseriouslylimitsresponse Crohn’sdisease.AlimentPharmacolTher.2006;24:1507–1523. toESAisfunctionalirondeficiency(FID),whichisanimbalance 5.Gomollón F, Gisbert JP. Current management of iron deficiency betweenironneedsintheerythropoieticmarrowandironsup- anemia in inflammatory bowel diseases: a practical guide. Drugs. 2013;73:1761–1770. ply.FIDmaybeeitherpreexistingoroccurringduringESAther- 6.Rizvi S, Schoen RE. Supplementation with oral vs. intravenous apy,when red cells are producedata ratethatoutstripslabile iron for anemia with IBD or gastrointestinal bleeding: is oral iron availability. As a consequence, iron supplementation may iron getting a bad rap? Am J Gastroenterol. 2011;106: stillbe requiredtoachieveormaintainanoptimalresponseto 1872–1879. ESA.Inanemiccancerpatients,irondeficiencyhastobeinves- 7.Gisbert JP, Bermejo F, Pajares R, et al. Oral and intravenous iron treatmentininflammatoryboweldisease:haematologicalresponse tigated by dosing transferrin saturation, a parameter that is andqualityoflifeimprovement.InflammBowelDis.2009;15:1485– modestly influenced by inflammation. Ferritin, in contrast, 1491. belongs to the group of acute-phase proteins and often does 8.BermejoF,GarcíaS.Irondeficiencyanemiaininflammatorybowel notreflectironstoresincancer,duetoitsinterdependencewith disease.EnfermInflamIntestDia.2015;14:11–20. inflammatoryreactions.Theironregulatorypeptide,hepcidin,is 9.LuggS,BealF,NightingaleP,etal.Irontreatmentandinflamma- toryboweldisease:whathappensinrealpractice?JCrohnsColitis. thekeyfactorunderliningtheoccurrenceofirondysregulationin 2014;8:876–880. the ACDs, including cancer. Hepcidin is upregulated in ACD, 10.CarrierJ,AghdassiE,PlattI,etal.Effectoforalironsupplementa- resulting in the inhibition of iron transport across cell mem- tion on oxidative stress and colonic inflammation in rats with branes, which decreases the accessibility of storage iron and inducedcolitis.AlimentPharmacolTher.2001;15:1989–1999. gastrointestinal absorption of dietary iron, leading to an 11.HarokopakisE,HajishengallisG,MichalekSM.Effectivenessoflipo- somespossessingsurface-linkedrecombinantBsubunitofcholera increased frequency of iron-restricted erythropoiesis, especially toxin as an oral antigen delivery system. Infect Immun. duringtherapywithESA.Hepcidindisregulationmaywellrepre- 1998;66:4299–4304. sent the mechanism by which oral iron supplementation has 12.Torchilin VP. Lipid-core micelles for targeted drug delivery. Curr beenreportedineffectiveincancerpatients. DrugDeliv.2005;2:319–327. Prospective trials published over the last decade demon- stratethatanemicpatientswithcancerundergoingchemother- Iron parameters in cancer patients and prediction of apy and receiving ESA respond better, without additional hemoglobin response toxicity, when parenteral iron is administered. Such benefit is more relevant when FID is present at baseline but appears to Paolo Pedrazzoli, Simona Secondino, Sara Delfanti, be independent of baseline iron variables in one large study. Giovanni Rosti EXPERTREVIEWOFHEMATOLOGY 9 Thisissueisclinicallyrelevantbecauseappropriateironsupple- Introduction mentation, apart from allowing more patients to benefit from Anemia is a common manifestation of cancer patients and is ESA therapy, may represent a strategy to improve the cost usually associated with advanced disease, malnutrition, and effectivenessofESAinoncology,asithasoccurredinnephrol- poor prognosis. It is one of the reasons for fatigue, delay/ ogy. However, the use of iron supplementation during treat- reduction and change in dose intensity of cancer treatments, ment with ESA is not rigorously pursued in anemic patients poor activity of radiation therapy due to reduced oxygen withcancerasithasinchronickidneydisease.Thisunderuseis effect, increase use of blood transfusions, and finally of rise likely to be related to: (i) the false perception that cancer of financial burden in oncology setting. Rapid correction of patients do not have decreased iron stores (as measured by hemoglobin (Hb) levels is necessary for patients’ well-beings, serum ferritin) and therefore thought not to require iron sup- and needs iron plus or minus erythropoiesis-stimulating plementation during ESA therapy, (ii) the often misinterpreted agents (ESAs) and eventually, if they do not permit to correct incidenceandclinicalnatureofseriousadverseeventsofintra- Hb, red blood cells (RBCs) transfusions. Usually, ESAs asso- venous iron, (iii) the lack of studies demonstrating the efficacy ciated with parenteral iron are appropriate to treat moderate oftraditionaloraliron agentstofavor response toESA. (grade(G2))anemia,converselymoresevereandsymptomatic Novel iron preparations capable of increasing iron absorp- grade of anemia (G3–4) needs prompt transfusions. ESAs sig- tionandbioavailability,includingthosecarriedbyaphospho- nificantlyreducedtheuseofRBCtransfusions(relativerisk(RR) lipid plus sucrester membrane, may well facilitate a more 0.65,95%CI0.62to0.68)accordingtoa2012Cochranemeta- widespread use of iron supplementation in cancer anemia. A analysis [1]. Nowadays, in chemotherapy-related form of ane- randomized study is currently ongoing aimed to define the mia, parenteral iron has showed a better and rapid response potential benefit of Sucrosomial® Iron in improving response of ESAs agents according to a meta-analysis of randomized to ESA in anemic cancer patients. trials[2].IronshouldbegivenduringESAtherapy,ifnecessary, in order to maintain a transferrin saturation of ≥20% and a serumferritinlevelof≥100ng/mL.Thereasonoffailureoforal References iron formulation in cancer anemic patients seems related to the hepcidin protein, an acute-phase protein produced pri- 1.CellaD,DobrezD,GlaspyJ.Controlofcancer-relatedanemiawith marilybytheliver.Severalobservationsuggeststhathepcidin, erythropoieticagents:areviewofevidenceforimprovedqualityof lifeandclinicaloutcomes.AnnOncol.2003;14:511–519. andperhapsotherregulatorymoleculesproducedintheliver 2.Cella D, Stone AA. Health-related quality of life measurement in [3–5], plays a major role as a negative regulator of intestinal oncology: advances and opportunities. Am Psychol. 2015;70:175– iron absorption and iron release from macrophages [6–7], by 185. interacting with, and inactivating, the iron export protein 3.SankaranVG,WeissMJ.Anemia:progressinmolecularmechanisms ferroportin[8].Molecular-targeted agentsas monoclonalanti- andtherapies.NatMed.2015;21:221–230. bodies (e.g. anti-HER2, epidermal growth factor receptor 4.TessitoreN,SoleroGP,LippiG,etal.Theroleofironstatusmarkers inpredictingresponsetointravenousironinhemodialysispatients (EGFR), or vascular endothelial growth factor (VEGF) agents) on maintenance erythropoietin. Nephrol Dial Transplant. orsmallmolecules(multi-target)tyrosinekinaseinhibitors(e.g. 2001;16:1416–1423. sunitinib or sorafenib) are able to interfere with specific path- 5.PedrazzoliP,FarrisA,DelPreteS,etal.Randomizedtrialofintra- way leading to a reduced/altered erythropoiesis as reflected venous iron supplementation in patients with chemotherapy- byhighrateofG1-2anemiainclinicaltrials.However,theuse related anemia without iron deficiency treated with darbepoetin alfa.JClinOncol.2008;25:1619–1625. ofEPOwithnewmolecularagentsisnotcurrentlylabeled,and 6.LudwigH,MüldürE,EndlerG,etal.Prevalenceofirondeficiency itssafetywithanti-angiogenetictherapiesisdebatable,dueto acrossdifferenttumorsanditsassociationwithpoorperformance apossiblegrowthstimulationofEPOmediatedbyEPOrecep- status,diseasestatusandanemia.AnnOncol.2013;24:1886–1892. tors (EPO-R). In this setting, not functional EPO-R but EphB4 7.Auerbach M. Intravenous iron in chemotherapy-induced anemia. protein, working as an EPO-R promoting tumor growth and AmJHematol2014;89:1153. 8.Petrelli F, Borgonovo K, Cabiddu M, et al. Addition of iron to progression via Stat3 signaling, was recently discovered by erythropoiesis-stimulatingagentsincancerpatients:ameta-analy- Pradeep and colleagues (Figure 1). In particular, abundance sisofrandomizedtrials.JCancerResClinOncol.2012;138:179–187. ofEphB4receptoronhumanbreastandovariancancertissues 9.PedrazzoliP,RostiG,SecondinoS,etal.Ironsupplementationand predicted poor survival, in particular, when EPO was asso- erythropoiesis-stimulatory agents in the treatment of cancer ane- mia.Cancer.2009;115:1169–1173. ciated [9,10]. As for now, data with EPO in patients treated 10.YuanL,GengL,GeL,etal.Effectofironliposomesonanemiaof with targeted agents for solid tumors were ever being con- inflammation.IntJPharm.2013;454:82–89. ducted,andthetreatmentoftheseemergentformsofanemia is unknown. Anemia with molecular-targeted therapies used for solid tumors: an updated pooled analysis of Etiology and frequency of anemia with molecular literatureandnewperspectiveswithsucrosomaliron agents Fausto Petrelli and Sandro Barni Thecausativeroleofanemiawithmolecularagentsispartially unknown, but the general opinion is that they can interfere OncologyUnit,ASSTBergamoOvest,Treviglio,Italy with myelo- and erythropoiesis in bone marrow. If other

Description:
Sandro Barni. To cite this article: Sandro Barni (2016) 4th Mediterranean Multidisciplinary Course on Iron In onco-hematology, anemia plays a pivotal role in altering in oncology, a condition where increased iron storage and reduced iron anemia with targeted therapy in more than 90 clinical tria
See more

The list of books you might like

Most books are stored in the elastic cloud where traffic is expensive. For this reason, we have a limit on daily download.