ILL Document Delivery Biroac Organizacan Pan Anericana Da Saude Rua Botucatu 862 - Vila Cleaentino REG-13858250 BREBIR Vi IT1355 (CENCOLL); Electronic Journal with ILL a Sao Paulo 04023-301 BRAZIL aTTH suewrtren 2ong-n7-18 17-15-06 PHONE: © 011-§5-11-5575~9835 PRINTED: 2006-07-19 10:18:19 FAK O11-S5-11-8571-1919 REQUEST NO.: REG-13858250 EMAIL: scad-bir@hiresc.br SENT VIA. DOCLINE TOCLINE Ho: 20396975 REG ‘Copy’ Journal TITLE DIGESTIVE AND LIVER DISEASE ; OFFICIAL JOURNAL OF THE ITALIAN SOCIETY OF GASTROENTEROLOGY AND TEE ITALIAN ASSOCIATION FOR THE STUDY OF THE LIVER PUSLISHER/FLACE Eleovior Anctordan VOLINE/ISSUE/PAGES 2006 Jun;38(6)° 381-7 381-7 DATE 2006 AUTHOR OF ARTICLE Berni Canani R; Terrin G; Borrelli 0; Ronano X; Yanguso F, C Ghort- and long-tern therapeutic efficacy of nutri issu 1590-3658 OTHER NUWBERS/LETTERS: TITLE OF ARTICLE HLM Unique ID: 100950365 PubMed ID: 16901010 SouRCE PubMed MAX COST. 516.00 COPYRIGHT COMP Guidelines CALL NUMBER: Wi ITL955 (GMICOLL); Electronic Journal vith IIL « NOTES 060712678 TELIVERY, Eowail: scad-birObirene. br REPLY Maal KESP THIS RECEIPT 10 RECONCILE WITH BILLING STATEMENT For problens or questions, contact NIM at http: //uycf nln nih gov/ill/ill_veb form.ctm or phone 301-496-5511 Include LIBID end request nunber NOTE: THIS MATERIAL MAY EE PROTECTED BY COPYRIGHT LAV (TITLE 17, U.S. CODE)‘Available online at wwwscienceditectcom sorence @ornser- Digestive and Liver Disease Digestive and Liver Disease 38 (200) 381-367 winter cones Alimentary Tract Short- and long-term therapeutic efficacy of nutritional therapy and corticosteroids in paediatric Crohn’s disease R. Beni Canani*, G. Terrin®, O. Borrelli®, M-T. Romano®, F. Manguso®, A. Coruzzo*, F. D'Armiento4, E.F. Romeo?, S, Cucchiara®* Deparment of Puedes, University of Naples ‘Federico I Noples. aly ® pission of Pedi Gastroenterology Unt, Univer of Rome ‘La Sapienza’ Vile Regina Elena 312, 0016] Rome, ly Deparment of Experinentl Meicine. University of Naples Federico I, Naples Nay * Deparment of Patolgs, Universit of Naples Federico I, Neples, lly Received 15 Jone 2005; accept 4 October 2008, “Aaa oline 1 November 2005 Abstract Background. Comparative data on the therapeutic efficacy of diferent enteral nutrition formulas and corticosteroids to obtain clinical remission and to induce mucosal healing influencing longterm disease couse in paediatric Crohn's disease are stil sare, ‘Aims, To investigate the efficacy of nurtional therapy using three diferent formulas versus corticosteroids to achive clinical emission 4s well st induce intestinal mucosal healing insetive Crohn's disease children. Duration of remission and effect on growth recovery were also assessed. Patients and methods. Clinica, lboratory, endoscopic and histological data ofall new diagnosed active Crohn's disease paediatric cases were reospectively recorded and feviewed. Thirty-seven children (median age 12.1 years) received nutritional therapy (12 polymerie; 13, ‘semi-lemental; 12 elemental diet) and 10 subject (median age 12.4 years) received comticosteoids. ‘Results, Similar lineal emission rate were observed after 8 weeks of treatment: 86.5% children receiving nutritional therapy versus 90% rested with coicosteoids. Improvement in mucosal inflammation occurred in 26 out of 37 (64.8%) patients on nutritional therapy and in 4 ‘out of 10 405) children on steroids (p <0.05). Finally, seven subjects on nutitioal therapy and none oa comtiosteroids achieved complete ‘mucosal healing (p-<0.005) atthe end of the treatment. Nutritional therapy was more effective than conticostroids in improving nutitional ‘Status and lineae growth recovery, Compared to cartcosterids, the daration of clnial remission was Tonger in the nuttional therapy eroups without diferences among the tree diferent formulas. Conclusions. Ta children with active Crohn's disease, nu inflammation and to maintain a more sustained clinical remission. (© 2005 Edivice Gastroenterologia alana Sc. Published by Elsevier Ltd. Alright reserved, jonal therapy is more effective than corticosteroids to improve intestinal Kwon: Cilien: Coniconesids;lalsmmatry bowel disse; Mucosal infimation; Natitonl therapy: Palyere dct 1. Introduction and intestinal mucosa healing [2,3]. Corticosteroids (Cs) are considered a major therapeutic option to induce remission Crohn's disease (CD) is a lifelong, chron in patients with active CD [4}. However, several subjects tory condition ofthe gastrointestinal tract with severe nurri- experience adverse events from these drugs with litle or no tional and metabolic implications, characterised by periods improvement in disease activity and in mucosal inflammatory ‘of remission and recurrent relapses (1. Optimal therapeu- lesions, or experience a flare in the disease activity during tie strategies are aimed to achive either clinical remission or soon after Cs dose reduction [4]. For many paediatric ‘gastroenterologisis. Cs are an even Tess attractive fisst-line onsponting ute, Te: 439069979326: 439 0877925, therapy because CD children already have significantly ow Email adres elvtre.coehara@onizomalt (. Cees). bone mineral density and growth delay at diagnosis (5-7) 15908658530 © 205 Esse Gsroenterlogiea llama Si, Published by Elsevier Li Al rihis 40,1016 142005.10.05 se Material may be protected by copyright law (Title 17, U.S, Code)se Berni Conant eral. Digestive and Liver Disease 35 (2006) 381-387 Several studies have supported a primary role for nutri- tional therapy (NT) in the treatment of active CD [8,9]. Tra itionally, NT consisted of elemental (amino acids mixture) or semi-elemental (hydrolysed proteins) diets, given contin- uuously through a naso-gastic tube. Subsequently, polymeric formulas, with better palatability and lower cost, have been sucessfully used in children with active CD [9]. Three mets- analyses and a Cochrane review have concluded that NT, as primary therapeutic approach for CD, is statistically infe- riot to Cs in inducing clinical remission (10-13). In another analysis, limited to randomised clinical trials involving only paediatric patients, exclusive NT resulted as effective as Cs n inducing elinial remission [14]. However, no sub-analysis by the type of formulas used was performed. In addition, itis ‘worth noting that most of these studies differ substantially in some erucial methodological aspects and, more importantly, donotemploy endpoints and definitionsused in amore recent therapeutic tials Ge effect on mucosal healing, long-term clinical response and inflammatory remission, evaluation of safety), Finally, in paediatric CD, data comparing the long- term remission rate obtained with NT or with Cs are still ‘This was a retrospective study that aimed primary to eval- uate efficacy of differedt nutritional formulas (polymeric, semi-clemental and elemental) compared with Cs to achieve clinical remission and mucosal healing as well as to mod- ify the disease course in children with active CD. Secondary, ‘we also wished to evaluate the effect of these therapeutic sirategies on nutritional status, growth pattern and on the ‘occurrence of adverse event. 2, Patients and methods “The study patients were all subjects under the age of 18 yeats who received a new diagnosis of active CD in our ‘Tate Enteral nition fomilsscompesion as suted onthe abel Department from December 1999 to December 2001, Data were retrospectively collected from patients’ medical records including basic demographics, clinical, laboratory, endo- scopic and histopathology findings. In particular in order to comparatively evaluate the efficacy and safety of NT and Cs, we collected data regarding: (1) clinical remission rate at 2,4 and 8 weeks of treatment; (2) endoscopic and histolog- ial remission rate at 8 weeks; (3) rate of patients in clinical remission during 12 months follow-up period; (4) nutritional sfatus and grovth and (5) occurrence of adverse events. Children with a history of previous intestinal surgery, administration of Cs or immunosuppressive drugs during the 3 months before CD diagnosis, incomplete clinical, endo- ‘scopic, histological and/or laboratory data, poor compliance (defined as assumption less than 80% of volume of daily pr scribed NT or Cs dosage for at least 3 consecutive days, or duration of full NT and Cs therapy less than 8 and 4 weeks, respectively) were not considered. In all patents, the diag- ‘nosis and the disease extension were defined through widely accepted clinical, radiological, endoscopic and histological criteria (15], Children receiving a 8-weeks NT course were classtiod retrospectively in three cohorts according to the type of formula used, ‘The composition of the three evaluated formulas is reported in Table I. Polymeric diet was given orally, whereas the other formulas were administered through naso-gastic tubo connected toa peristaltic pump, providing 50-70 kealhkg ideal body weight per day. During this period patients were only allowed unsweetened tea or water, but no other food. Following the initial 8-weeks treaiment period, foods were reinuoduced slowly at a rate of one new food every 2 days, as previously described [16]. Children in the Cs group received methylprednisolone (1-2 mg/kg/day, maximal dose 40mp/day) for 4 weeks with subsequent gradual tapering overat least 4 weeks. Endoscopic diagnostic procedures were performed by the same experienced team and were recorded Elemental (ieee, “Senelemenal Polymers (Modulen IBD, Nii, tly) (eezoin,Mlpa, y) Nest tay) eraydeasiy Gead00) 15 37 500 ‘Total protein (1000s) 2 27 36 Percentage emery 102 109 1" ‘etl earbohy date (/1000 eal) us Ho. 10s Peeenageenesy 456 4857 4“ “Toul fa (/tO00 eal), 8 4" Pereetage nergy 43 34 ‘Tul SCFA (10004) 00 00s Toul LCT (g0004ca) os 382 ‘Taal MCT (/10005a) 94 4 ucraict 32H fl “Tal strated uty aids 147 0 Polyenstrated (PUFA (es) 90 59 ‘Morounstraed(MUFA)() 223 20 6 (p/000kea) 02 47 3 t000ke)) 07 09 elo soe 55: Material may be protected by copyright law (Title 17, U.S, Code)Li [Berni Canon et ol. Digestive and Liver Disease 38 (2006) 381-387 a fon tapes. The grading of the gut inflammation was deter- ‘mined by two experienced observers who were unaware to clinical information. The inflammation was scored at six standard sites using a scoring system previously described bby Saverymuttu et al. (17). During ileocotonscopy at least twvo biopsy specimens were taken from each segment of the ileum and colon for histological examination in all subjects included in the study. The standard sites were ‘rectum and. sigmoid’, ‘descending colon’, ‘transverse colon’, ‘ascend- ing colon and cecum’ and ‘terminal ileum’. The specimens were fixed in formalin and stained with haematoxylin and eosin. The mucosal inflammation was scored always select ing the most inflamed segment of the ileum or the coton to represent the grade of inflammation in each patient. Severity (of mucosal inflammation was assessed according to previ ‘ously validated endoscopic (score O: normal appearance; 1: loss of vessel pattern or oedema; 2: contact haemorthage; 3: ulceration or surface mucopus) and histological (entero- ‘yte: 0: normal; I: loss of single cells; 2: loss of group of cells; 3: frank ulceration, Crypr: 0: normal I: single inflam- ‘matory cells; 2: erypttis; 3: erypt abscesses. Lamina propria mononuclear cells: 0: normal; 1: slight increase; 2; mod- crate increase; 3: marked increase. Neutrophils: 0: normal; I: slight increase; 2: moderate increase; 3: marked increase. Conversion of histological grades, summate enterocyte, crypt and lamina propria grades, to final score: grades 0-1, score 0; grades 2-4, score 1; grades 5-8, score 2; grades 9-12, score 3) scores [20]. Improvement in endoscopic and his- tological score was defined as reduction > I grade, whereas remission was considered when score was 0. Disease activity was measured with the Paediatric Crobn's Disease Activ- ity Index (PCDAD [18]}. Clinical remission was defined as a PCDAL<10. To assess nutritional status and growth the following parameters were analysed: anthropometric mea- sures (weight and height) serum albumin and iron at base- Tine and after 8 weeks of treatment, The pubertal staging system ulilised was that published by Marshall and Tanner 19,20), 2.1. Statistical analysis Statistica analysis was performed by a statistician blind to individual treatment, The x2-test was applied for categorical variables, For continuous variables the differences between the study groups were analysed by one-way ANOVA with Bonferroni test for multiple comparisons. The General Lin- ‘ear Model (GLM) repeated measures was used to compare PCDAL value with Bonferroni test for multiple comparisons. “Abetween-subjects factor was added in the model in order to investigate the effect of different therapeutic approaches on the variable analysed. The paired -test was used to compare ‘endoscopic score, histological score, serum iron and albu- ‘min levels at baseline and after 8 weeks in the different four groups. Differences within groups at baseline and at 8 weeks were calculated with one-way ANOVA and Bonferroni test as past hoc analysis. The Kaplan and Meier procedure was used to calculate remission rate during 12 months follow up for different treatment strategy. Log-tank test was performed tocstablish the differences between groups. Statistical anal- ysis was performed with SPSS Version 12.0.1 for Windows (SPSS Inc., Chicago, IL, USA). 3. Results 3.1, Study population ‘The medical records of 52 patients were available for the study. Five subjects were excluded for the final eval- uation (three no full endoscopic and histological data and to poorly clinical recording data). Finally, 47 patients were ‘considered for the study. The main demographic and elin- ical characteristics of the subjects evaluated are reported in * Table 2. Thirty-seven patients received a 8-weeks NT course, whereas 10 children received Cs. The groups showed com- parable main demographic and clinical variables (Table 2). Using Tanner staging system we observed that NT (median 2,1QR 1) and Cs groups (median 2, IQR 1) were comparable also for pubertal stage. 3.2. Clinical, endoscopic and histological evaluation ‘The PCDAT score significantly decreased during the fol- ow up (p<0.001) in all patients as judged by the clinical assessment performedat2,4and8 weeks. Moreover all teat- ‘ments showed similar effects on PCDAI score (Fig. 1), and after 8 weeks of treatment clinical remission was achieved in ‘32 out of 37 (86.5%) children on NT andiin9 out of 10 (90%) Tebte2 Baseline linia nd demogrphi characteris of the stay poputions G wT Benenat Semi-clementl Polymer 0 2 a 3 ‘Age (ange) yea nae) nic H8@-15) nse) Mate sx 6 6 6 ° Location (SBICC)? ens Inn ens ams PCDAT mean 5D) 300108 3202107, 300122 joas7 7 SBICICE smal bow Ueotonifcoolni Material may be protected by copyright law (Title 17, U.S, Code)8 te Sorisorenstdet 8 He Consors eles Paediae Cros Osease Act index rater 2, 4 and 8 weeks (ks). Daa ‘re expressed as mean yb) and standad dviton (eric lines). + pc 0.00t for comparisons among diferent ime pont. of those treated with Cs. On the contrary, in the NT-treated childten a more pronounced effect on endoscopic score was ‘observed compared tothe Cs-treated patients, again without differences among the three NT groups (Table 3). Moreover, only in the NT-teated children a significant reduction in histological score was observed after 8 weeks of treatment (Table 3) In particular, improvement in mucosal inflamma- ton occurred in 26 out of 37 patients receiving NT but only in 4 out ofthe 10 children on Cs (p-<0.001), and 7 patients ‘on NT and none in the Cs group achieved complete endo- scopic and histological remission after 8 weeks of treatment (p<0.005). 3.3. Long-term maintenance of elnical remission In chitdron who achieved patients) or Cs (9 patients) therapeutic course, maintenance therapy with mesalamine (50-75 mg/kg/day) was started. AS shown by the Kaplan-Meier curve, the duration of clinical remission was longer when the later was initially achieved with NT, without differences among the three NT groups ig. 2). Berni Canan eta, / Digestive and Liver Dicase 38 (2006) 381-387 see Poyeeieet oes tt a E rr a a Fosow up (months) Fig. 2 Koplan-Meyer curve soning amore prolonged cial remision dutng ie 12 mont of follow vpindocedby NT compared to Csinchilen wth astive CD, 3.4. Nutritional status, growth recovery and adverse NT was more effective than Cs in improving nutritional status, as demonstrated by serum iron and albumin levels, (Table 4). No differences were observed in body weight recovery between NT and Cs groups (+12% versus +13% above the baseline weight measures, respectively). However, linear growth recovery was more pronounced in patients receiving NT than those treated with Cs (Fig. 3). A large ‘number of patients presented adverse events in the Cs-treated group (90%) (six moon faces, three acne, caemia, one muscle weakness) compared wit (2.4%) (soven nausea/vomiting, two diarthoea, two abdom- inal discomfort) (p=0.003), 4, Discussion Recently, mucosal healing has emerged as the main thee- peutic target in order to substantially modify the CD course {321-23}, Despite similar clinical remission rate, we have observed @ more pronounced effect on mucosal healing induced by NT compared to Cs. This result is not com- ‘rates ‘Shor-trm therapeu effects Of NT and Cs on neta mucosa aman © xT Element Semielement Polymeric TEndoropi score atelie 2400052) 2670049), 285(038), 238050, Alter B weeks 1700082) 075,002)" 08206)" 083 073)" ? 002 2001 0.001 <0 Histological sore ‘Baseline 32006) 3250075), s3807, 333007, Alter # weeks 27003) 108.0067) Hasq0y" La (46) if 006 2001 <0 <0001 Dus areeaprened a ean (SD). “pe005ee Cs Material may be protected by copyright law (Title 17, U.S, Code)Berni Conant eta. /Digeave and Liver Disease 38 (2006) 381-387, sas ‘Tate Evaluation of utiiona stu nthe stad populations c wt Eenentad Senelenentl Polymers ‘Sum iron Basie 20801185) 312508), 2946 039), 225810) After wecks 58801160) mveoay 66.09 (193) e2saxey > ot 001 oon? 008 Serom sbumin ‘Bascine 337029 318047, 3:13 040), 3.09039), Alter weeks 340(022) 398,036" 338(025) 386,038)" ? 028 2001 <000 2001 Danse opresed as neon (SD), *peQ03¥5.Cs pletely unexpected. A poor correlation between clinical and ‘endoscopic remission has been previously demonstrated in CCs-treated patients indicating that active endoscopic lesions ccan be detected in up to 70% of subjects who achieved clin- ical remission with Cs therapy (24-26]. The investigators suggested that the lack of correlation between endoscopic and clinical results may be explained by the poor ability of Cs to modify submucosal inflammatory processes 24) (On the contrary, previous data showed that clinical response to NT using polymeric dit is associated with a decrease in serum tumour necrosis factor alpha levels, whilst in intestinal mucosa there was a significant evidence of mucosal heal- ing together with a down-regulation ofthe pro-inflammatory cytokines interleukin-I-beta, interleukin-8 and interferon- ‘gamma (27-2). Inour study, the more pronounced NT effect ‘on mucosal healing was favourably associated with clini- cal relapse rate by 1 year: 30% versus 70% observed in the Cé-treated patients. These data confirm the importance to achieve mucosal healing in order to provide a sustained long-term remission. We would speculate that the persis- tence of subclinical mucosal inflammation may be involved in the high relapsing rate observed in the Cs-treated chil- 2° : : i gz ae ‘Elomarial at _Servelemectal det Polar ut ee ra Fig. 3, Linear growth ecover observed inthe hee NT groupe and in Co tested patient st 8 weeks fom he baseline, Daa are expressed 38 mean (@as) and standard deviation (ine). "p<005 vs. Ce dren, The crucial importance of mucosal healing is also supported by the beneficial effects of NT on nutritional sta- tus and linear growth. Several interrelated factors may co tribute to linear growth and nutritional status impairment in CD children. Recently, direct growth-inhibiting effects of pro-inflammatory eytakines released from inflamed intestine hhave been suggested increasingly recognised (30). Our data support this view suggesting that an enhancement of linear {growth is best achieved through intestinal inflammation con- trol and assurance of adequate nutrition support by NT [7] In this regard, the optimal nutritional intake provided by the commonly used diferent formulas to reat CD together with the lower incidence of adverse events, as also demonstrated in this study, represent an important advantage for NT as first-line therapy for childsen with active CD compared to cs. "To date the exact mechanisms of action of NT in CD are still largely undefined, Several hypothesis have been consid- cred [8,31]. The fact thatthe effects of different diets were ‘comparable argues against the theory of a reduced antigen ‘exposure. Other suggested mechanisms include provision of trophicamino acids, alterationsin gut flora and immune mod- ulating effects of fatty acids supplied by the formulas. In particulay, the optimal dietary fat content to induce cli ‘cal remission in active CD has been a controversial issue [8,32-35},Ithas been hypothesised that changes in dietary fat may affect eicosanoid synthesis and other immunomodula- tory mechanisms, thereby influencing disease outcome [33]. Ingestion of w-3 fatty acids has been reported to suppress ‘mucosal inflammation, whereas ingestion of w-6 fatty acids hasbeen shown to stimulate the inflammatory process. Either low total fat content and a low ratio of w-6 to w-3 polyun- saturated fatty acids (PUFA) have been thought tobe able 10 reduce intestinal inflammation [32-35]. Ourresults, showing comparable efficacy of the three different formulas, seem 10 not support the view that fat composition could be critical t0 promote clinical and inflammatory remission. Indeed, several experimental observations suggest a critical role of commen- sal gut microflora in eliciting an inlammatory response of intestinal mucosa in subjects wth an underlying immunolog- ical mucosal defect [36,37]. Future studies are necessary t0 Material may be protected by copyright law (Title 17, U.S, Code)386 [R.Ber Conan ta, / Digestive and Liver Disease 38 (2006) 381-387 investigate whether NT is able to modify gut mucosa atached microflora. In conclusions, despite the limitations deriving from ret- rospective design, our study shows a more impressive effect ‘of NT, compared to Cs, in inducing mucosal healing and {improving nutritional status in active paediatric CD. Its of clinical relevance that remission rates at 12 months follow ing the initial therapeutic course were significantly higher in patients treated with NT than in those who received Cs, ‘despite the same maintenance therapeutic schedule adopted in all patients. Ina disease which runs a chronic relapsing course, it is crucial to achieve full remission on all parame- ters with initial therapy, with subsequent therapy aiming to ‘maintain this, A therapeutic approach that is able to improve clinical symptoms but masks low-grade ongoing disease may not substantially afect disease progression over the longer term In this view, our data stcongly support NT as first-line ‘treatment for active CD children. Conflict of interest statement None declared, List of abbreviations CD, Crohn's disease; Cs, corticosteroids; GLM, Gen- eral Linear Model; NT, nutritional therapy; PCDAI, Paediatric Crohn's Disease Activity Index. References [0] Shanahan F Crobn’s dist, Lancet 2002389629. [2] Escher I, Taina JIM, Nicuwenbois EES, Buller HA, Grand “Tresiment of ntiaramstory bowel dessin childhood: est avaible siden. Infaman Boel Dis 20039:31-58, (0) D'Haens G, Vn Deventer S, Van Hogeznd R, Chalmers D, Kobe (, Baen Fetal: Endoscopie and histological being wit infxima asomar nese fctor anodes in Crain's disease: a European ‘tents wil, Gastroenterology 19993116 1029-34, 14] Regeens PJ, The lniation of coriosteoid therapy in Crohn's diese, Aliet Pharmac! Ther 200;151515-25. (5) Stephens M, Baues LA, Ng D, Baldassano R Gronth failure in the cll wih iflmatory bowel disease. Semin Gxsrinest Dis 2001:12253-02 [61 Tyes GNI, Bane JFWM, van Deventer SIH, editors. IBD, port ofthe Falk Symposim 85, Progress ia understanding pace Aine IBD problems. Dorzeck, Neelands: Kluwer Academic 1995, p, 329-33, (7) Walker Smith 4, Bnsgement of growth fire in Crba's diese Arch Dis Child 19965381-4 [81 Gafihs AM, Enteral notion inthe management of Crohn's i+ fase Parenter Esterl Nutr 2005:29:S108-17 (91 O'Sulvin M, O'Morin C. Nuintionsl thrspy fa infamams tery bowel disse. Cur Trest Options Gastroenterol 20057:191— & [10] Feminder-BsfaesF, Cab, Eteve-Comss M, Gall MA, How fective is efera eutson in indocing linia remision in sive Cob’ teas? A metasnsssis ofthe randomized clinical tae 4 Pareier Enteral Nate 1995;19:386-65, un) Gaimias AM, Onsson A, Shermn PM, Sutherland LR. Meta analysis of enteral mutton a primary weatment of active ich’ ize, Gastronteraogy 1995:108:1056-67. U2] Messori_A, Talos. G, D'Albasio G, Mila M, Vansozai G, Pacot F. Deinedformsls diets vero slerids in the eestment of ative Crotn's diese: a metranayis Scand } Gnsteenteat $9631:267-72 131 Zachos M, Tendeur M, Gifts AM, Eater! eusonat erapy for dation of remision ia Croba’s eae (Coceane Review). The CCochane Latvary, tue 4; 2005, (18) Heuseel RB, Menache CC, Megevan JT, Bind AB. Enteral nati tion and cortcoerid in the treatment of sate Cras disease in ‘hile, J Pediatr Gastroenterol Nat 200031:5-18, {15} GoverRowsea C, Salome IL, Dugas JL, Mari, Notens MC, ote A ea lncdenee of tafammatory bowel ditesse im norte France (1988-199), Gat 199435:1433-8 06) Stadenon IR, UdeeaS, Daies FS, Savage MO, Walker Sith JA Remission induced by an element dit in small bowel Coke's Aiscae, Arch Dis Cid 19761123. LUM Saverymatts SH, Comes M, Rees H, Lavender JP, Hodgson WS, Chadwick VS. Tndiom Il -rsnloeyteseaaing inthe assessment tf disease exet and disease act in inaramatony bowel disease ‘A comparison with colonoscopy, histology, and fea! indium 111- ganolcye excretion. Gastroenterology 1986;90:1121-8. [08] Hyams JS, Fery GD, Mandel FS, Gpboski JD, Kitor PM Kinshner BS, et al Development aod validation of a. pedi sire Croha's disease ati index. J Peat Gastoentrol Nut 199112343907. (19) Mazsbll W, Tanne J. Vasaons i he pater of pubertal ehanges In git. Arch Dis Child 1969:44291-308 [20] Marshall W, Tanner IM, Variton ia he pater of pubertal changes in boys, Arch Dis Child 197035:13-23. [21] Sandbor W, Sutherland L, Pearson D, May G, Medigian!R, Pras tera C, Azsthiopine or 6merep tops fr inducing remission of Grom's diease, The Cochrane Library. Oxford: Update Sofware; 203. [22] Buen FH, D'sens GR, Peters M, Wile Ml, Schaible TR Stely Dy eta. Tumor crs factor alpha seubody (afin) Werapy profoundly down-egeltes te fami in Coke's locos, Gastroenterology 1959311628. [23] Verma §, Brown S, Kikwood B, Giffer MH, Polymeric vee. ug elematal ict a6 primary testment in sce Crob's dis- ‘sae: a randomized, dobleting wal Am J Caseceterol 200095 ns. {21 Landi, Anh TN, Conot A, Soule JC, Rene E, Genre Jet a Endoscopic monitrag of Crohn's discs twstment a prospec tive, radomied clin wal, The Groupe d'Etudes Theapeu tigus des Affcioe Instore Digesties, Gaseoeateroloy 1992;102:4647-53, [25) Modi R, Mary 5Y, Sinon JF, Const A, Soule IC, Geode 1, etal. Cina, Biologia, and endoscope picture of stacks of CCotn's diac, Evolution on predaisclone. Groupe d'Etude These reutique des Afestons Intammaoies Digesines Gastcenerlony 1990:983811-8. [261 Celie C, Sahmoud T, Froguel B, Adeis A, Besiche J, Brewsne 4 eal. Cotltons between elnical activity, endoscopic severiy, ‘af bioogial parameters in colonic or Hlecelonie Croba's dis: fuse. A provpectve mulicente stay of 121 ess. The Groupe CEtudes Theapeuiqaes des AMfecions Infsmanaoies Digestive, Gut 94a5;231-5. (201 Fall JS, Pann M, Amaod-Batandie F, Beatle RM, Holis A, Kitching Ret al, Mocorl healing and Gall In micosal po- fafammatory etokine mRNA indoced by a specific or poly- tae dit in padre Crob’s disease. Alimeat Pharmacol Ther ooo; Material may be protected by copyright law (Title 17, U.S, Code)1 Berni Canal eta. / Digestive and Liver Dieeare 38 (2008) 381-387 a7 [25] Meister D, Bode J, Shand A, Ghosh §. Anivinfmanstory effects of énteral it components on Cros daeneaeted sues a ito Dig Liver Dis 20023834308, 129) Bannerer K, Camscho-isee C, Babinska K, Deyburst KM, awards R, Sage MO, et a Anbiflammotory and grosth. stialaig eet recede ational rettation daring enteral feed {ng in Cro disease Pia Gastceatrat Ney 200438-20-5 (G0) Balinger AB, Azooe O, ELH), Pole S, Furbing 1. Growth false cccrs through & decrease in insulin tke growth factor ith ie independen of underurtion in rat model of eos. Gat 2000;16:694-700. [31] Fortes A. Review ante: Crohn's diese: te role of ution! therapy, Aliment Pharmacol Ther 2002:16(Suph. 448-82. [32] Midaeton 1, Rucker JT, Ktby GA. Longa igyerides reduce the efieay of etal feds lt pains with acve Crobn’s seas. (lin Now 195:14220-36. [83] Janes Ml, Gibson RA, Cleland LG. Dietary polyunsaturated faty acide and infammatory meistor producton Am I Clin Note 2000.7 (Sepp): 3438-88. [34] Sadeghi §, Waltce FA, Caller PC. Dietsry lipids moi the cytokine reson to bactrilHpopolysecharde in mice. Imeusel- ogy 1999 96:04-10 [25] Karten 5, Scbsfer G, Schuler P. Cytokine production and DNA rye by amsn pega Imphocyes in tesponse to alii, Sec, ole, and indie acd. JCal Physiol 1994161 15- 2. 136) Saoe RB, Therapeatc manipulation of the enteric miroora in inflammatory bowel dices antbiocs,reobites, and prebiotics, Gssvoenterology 2004:1261620-23, (31) Saunier K, Dore J. Gasuoitesina! watt snd the ede: fan tional foods, got microflora and heathy ageing. Dig Lier Dis 200234(Spp. 2):819-24, Commentary Nutritional therapy in paediatric Crohn’s disease: More food for thought? J.C. Escher* Deparment of Pedinric Gastroenterology: Sophia Children's Hospital Erasmus Medial Comet Rowerdan, The Netherlands Asse eine 29 March 2006, For over 30 years, enteral feeding has been uiilised in the treatment of inflammatory bowel disease. Meta-analysis of| trials in adult Crohn’s disease showed enteral nutrition to be less effective than corticosteroids (1]. These results may not be representative of the disease in children, who have to deal with the important issues of growth and pubertal development. The effect of nutritional treatment on Croba's disease activity in children has been assessed in numer- fous studies, many of these with a randomised controlled trial design, evaluating corticosteroids versus enteral feed- ing [2]. As always in paediatric clinical research, patient numbers were small and none of the studies have been able to show a significant difference in treatment efficacy. Pool- ing of data, as performed by Heuscikel etal. (3), demon- strated mean remission rates after nutritional treatment and conicosteroids in children with Crohns disease to be si lar, approximately 85%. However, compared with corticos- teroids, enteral nutrition has a positive effect on growth, {quality of life [4] and mucosal healing {5}, in the absence of disfiguring and sometimes irreversible side effects of cort- ccosteroids. Enteral feeding seems to be the ideal treatment for a child with newly diagnosed Crohn's disease. Indeed, it is the primary treatment of choice in children with Crohn's disease in the UK and Canada, and most children there seem Fels 1 10 4637095; fae 431-10 463681, Enel addres: jescherGensmusmet to drink the (polymeric) formula. It is puzzling as to why nutritional treatment has never gained much popularity in ‘other European countries or in the United States. Ithas been learnt through personal experience that when given a choice between a nasogastric tube and nothing else to eat or drink for 6-8 weeks or taking pills (with all the side effects), ado- lescents disappointingly tend to choose the latter. Among colleagues, it has been jokingly said that the prospect of ‘not having to eat for a while is not so bad considering the English cuisine. In the USA, itis often the doctors who feel ‘uncomfortable about prescribing 8 weeks of tube feeding, and for some reason American adolescents will not drink the required litres of formula. Berni Canani et al. (6} have taken on the challenging task of not only comparing enteral feeding and corticos- tercids, but also investigating possible differences between elemental, semi-elemental and polymeric formula. The 47 children receiving either corticosteroids (n=10) of ntti- tional therapy (n= 37) attained clinical remission at 8 weeks in 90% and 86.5%, respectively (p= 1.00). No differences were found between the three formulas used, as was already shown by Ludvigsson etal [7]. All of this adds tothe stim body of evidence that enteral nutrition is clinically effec- tive, an outcome that is not really surprising. The authors have, however, also assessed endoscopic as well as mucosal ‘healing in all paticnts. One of the aims of the study was 10 assess (and hopefully prove) the disease-modifying effect of Material may be protected by copyright law (Title 17, U.S, Code)