Original Article. D. Mège, a M. N. Figueiredo, a,b G. Manceau, a L. Maggiori, a Y. Bouhnik, c Y. Panis a. Abstract. 1.

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1 Journl of Crohn's nd Colitis, 2016, doi: /ecco-jcc/jjw040 Advnce Access publiction Februry 13, 2016 Originl Article Originl Article Three-stge Lproscopic Ilel Pouch-nl Anstomosis Is the Best Approch for High-risk Ptients with Inflmmtory Bowel Disese: An Anlysis of 185 Consecutive Ptients D. Mège, M. N. Figueiredo,,b G. Mnceu, L. Mggiori, Y. Bouhnik, c Y. Pnis Deprtment of Colorectl Surgery, Beujon Hospitl, Université Pris VII, Clichy, Frnce b Postgrdute Gstroenterology Deprtment, University of São Pulo Medicl School, São Pulo, Brzil c Deprtment of Gstroenterology, Beujon Hospitl, Université Pris VII, Clichy, Frnce Corresponding uthor: Yves Pnis, MD, PhD, Service de Chirurgie Colorectle, Pôle des Mldies de L Appreil Digestif [PMAD], Hôpitl Beujon, 100 Boulevrd du Générl Leclerc, Clichy, Frnce. Tel: ; fx: ; emil: yves.pnis@ bjn.php.fr Abstrct Bckground: There re very few studies nd no consensus concerning the choice between twond three-stge ilel pouch-nl nstomosis [IPAA] in inflmmtory bowel diseses [IBD]. This study imed to compre opertive results between both surgicl procedures. Methods: Only ptients who underwent lproscopic IPAA for IBD were included. They were divided into two groups: two-stge [IPAA nd stom closure] [Group A] nd three-stge IPAA [subtotl colectomy, IPAA, stom closure] [Group B]. Results: From 2000 to 2015, 185 ptients (107 men, medin ge of 42 [rnge, 15 78] yers) were divided into Groups A [n = 82] nd B [n = 103]. Ptients in Group B were younger thn in Group A (39 [15 78] vs 43 [16 74] yers; p = 0.019), presented more frequently with Crohn s disese [16% vs 5%; p < 0.04], nd were more frequently operted in emergency for cute colitis [37% vs 1%; p < ]. Cumultive opertive time nd length of sty were significntly longer in Group B (580 [ ] min, nd 19 [13 60] dys) thn in Group A (290 [ ] min nd 10 [7 47] dys; p < ). Cumultive postopertive morbidity, dely for stom closure, nd function were similr between the two groups. Long-term morbidity ws similr between Group A [13%] nd Group B [21%; p = 0.18]. Conclusions: Our study suggested tht postopertive morbidity ws similr between two- nd three-stge lproscopic IPAA. It suggested tht the three-stge procedure is probbly sfer for high-risk ptients [ie in cute colitis]. Key Words: Ilel pouch-nl nstomosis; inflmmtory bowel diseses 1. Introduction Tody, ilel pouch-nl nstomosis [IPAA] is the opertion of choice for refrctory ulcertive colitis nd indeterminte colitis, 1 nd for selected ptients with Crohn s disese. 2 The IPAA procedure is usully performed electively in two stges. In the first stge, ptients undergo restortive totl proctocolectomy with IPAA nd J-pouch nd temporry diverting loop ileostomy. In the second stge, performed 6 to 8 weeks lter, the stom is reversed Copyright 2016 Europen Crohn s nd Colitis Orgnistion (ECCO). Published by Oxford University Press. All rights reserved. For permissions, plese emil: journls.permissions@oup.com 898

2 Two- vs Three-stge Ilel Pouch-nl Anstomosis 899 nd bowel continuity is restored. 3 We nd others hve suggested tht lproscopy is tody the best pproch for two-stge IPAA, 4,5 with lower postopertive morbidity 6 nd infertility rtes 7,8 thn fter open IPAA. A three-stge procedure, including subtotl colectomy with double-end ileostomy nd sigmoidostomy t the first opertion, followed by IPAA, nd then stom closure, cn lso be proposed, especilly in ptients with cute colitis, or uncler dignosis of inflmmtory bowel disese [IBD], or in high-risk ptients with recent steroid therpy nd/or poor nutritionl sttus. 9,10 As for the two-stge procedure, the lproscopic pproch is incresingly proposed for the three-stge IPAA. We previously demonstrted the possible benefit of lproscopy for subtotl colectomy, 11 which ws recently confirmed by met-nlysis. 12 Furthermore, we observed tht performing both subtotl colectomy nd second-step IPAA by lproscopy 13 cn significntly reduce cumultive hospitl sty,with lower cumultive postopertive severe morbidity thn following n open pproch. 14 Although the three-stge is generlly proposed minly in highrisk ptients with complicted cute colitis or refrctory to medicl tretment, under recent steroids or nti-tumour necrosis fctor [TNF] therpy, or with poor nutritionl sttus, some uthors prefer the two-stge pproch becuse it reduces the number of procedures, nd probbly overll hospitl sty nd costs, which cn be importnt in young, ctive ptients. 3,15 However, tody mong the mjority of the uthors, there is no consensus with regrd to choosing either two- or three-stge IPAA in IBD ptients. To the best of our knowledge, only five studies hve been devoted to dte to the comprison between two- nd three-stge IPAA. 3,15,16,17,18 In two of them, both IBD nd polyposis ptients were included. 15,18 IPAA ws performed by open pproch in three studies 15,16,17 nd by lproscopy in only 17% of the cses, in one series. 3 Thus, the im of this study ws to compre opertive results of two- vs three-stge IPAA in homogeneous series of IBD ptients ll operted by lproscopy [for both subtotl colectomy nd IPAA]. 2. Ptients nd methods 2.1. Study popultion All ptients who underwent lproscopic restortive proctocolectomy with IPAA for IBD [ulcertive colitis, undetermined colitis, or selected cses of Crohn s disese] were identified from our prospective single-centre institutionl review bord-pproved dtbse. Ptients with fmilil denomtous polyposis nd those with one-stge IPAA [without temporry stom] were not included. Furthermore, those with previous ileorectl nstomosis who underwent lter completion proctectomy nd IPAA nd those with n incomplete first stge, or with modified two-stge [first, subtotl colectomy; nd second, IPAA without stom] were lso excluded. Two groups of ptients were constituted ccording to the surgicl procedure: two-stge IPAA [Group A]: first, lproscopic totl restortive proctocolectomy with IPAA; nd second, stom closure; three-stge IPAA [Group B]: first, lproscopic subtotl colectomy with double-end ileostomy nd sigmoidostomy; second, lproscopic completion proctectomy nd IPAA; nd third, stom closure. A comprtive study ws performed between Group A nd Group B for the following findings: ptient fetures [gender, ge, body mss index, nutritionl sttus, pst medicl history, pst surgicl history, type of inflmmtory bowel disese, durtion of disese before surgery]; preopertive tretment in the pst 3 months (steroids, 5-minoslicylic cid [5-ASA], ntitumour necrosis fctor gents, immunomodultors [zthioprine, methotrexte, 6-mercptopurine, cyclosporine]); intropertive fetures [indictions, number of stges, type of nstomosis, conversion into lprotomy, defined s n unplnned bdominl incision longer thn 5cm, intropertive incident, nd opertive time]; postopertive outcomes [length of hospitl sty, in-hospitl nd 30-dy postopertive morbidity nd mortlity] nd long-term results [functionl results, pouchitis nd nstomotic stenosis rtes, definitive stom for filure]. Acute colitis ws defined by frequent bloody bowel motions, fever, tchycrdi, nd nemi. Its dignosis ws clinicl, biologicl, endoscopic nd rdiologicl. Acute colitis cn be complicted by toxic megcolon, bowel perfortion, or hemorrhge Surgicl procedure All the procedures were performed by two surgeons [YP, LM]. For two-stge IPAA, totl lproscopic pproch, s previously described, ws used. 18 Briefly, using five-trocr technique, totl restortive proctocolectomy nd IPAA were performed during the sme opertion, with temporry ileostomy t the site of specimen extrction, in the right ilic foss. For three-stge IPAA, lproscopic subtotl colectomy with double-end ileostomy nd sigmoidostomy in the right ilic foss were first performed, s previously described. 5,11,19 Both ileostomy nd sigmoidostomy were opened. After 2-3 months, lproscopic completion proctectomy with IPAA ws performed, nd temporry ileostomy ws performed t the sme site of the former double-end ileostomy nd sigmoidostomy. 14 Totl mesorectl excision, nd/or crcinologic mesocolic excision, ws only performed in cse of ssocited colorectl cncer or high-grde dysplsi. The temporry ileostomy ws closed if systemtic CT scn performed t 2 months with contrst enem did not show ny suspicion of nstomotic lekge or stenosis. Through elective incision in the right ilic foss, hnd-sewn end-to-end nstomosis ws performed using single-lyer interrupted sero-submucosl 5-0 PDS [Ethicon Inc., NJ, USA] suture. Fsci ws closed using 1-0 Vicryl [Ethicon Inc., NJ, USA]. The wound ws prtilly closed ccording to purse-string closure Outcome mesures Postopertive morbidity ws defined s ny compliction occurring during the hospitl sty or within 30 dys fter surgery. We distinguished non-septic surgicl complictions [hemorrhge, hemtom, ileus or smll bowel obstruction, stom-relted complictions such s dis-insertion, necrosis, or bleeding], septic surgicl complictions [peritonitis, nstomotic lekge t the site of IPAA, intrbdominl wound, or peristoml bscess], nd medicl complictions [urinry/pulmonry infection, crdic/neurologicl troubles, etc]. Complictions were clssified ccording to Clvien-Dindo s clssifiction. 21 Mjor complictions were defined s those requiring surgicl or rdiologicl intervention [Clvien-Dindo III] nd life-thretening complictions requiring intensive cre mngement [Clvien-Dindo IV]. In order to compre morbidity rtes between two- nd threestge IPAA, postopertive morbidity included ll the complictions observed fter the first opertion for two-stge IPAA nd, for threestge IPAA, morbidity observed fter both first [subtotl colectomy] nd second [completion proctectomy nd IPAA] opertions. Becuse postopertive morbidity fter stom closure ws expected to be similr fter two- nd three-stge IPAA, it ws not included in

3 900 D. Mège et l. the morbidity study. Similrly, length of hospitl sty included first opertion only fter two-stge IPAA nd first nd second opertion fter three-stge IPAA. A seprte nlysis of postopertive morbidity fter stom closure ws performed. For long-term functionl results, number of stool per dy nd per night, fecl incontinence episodes per 24 h, nd need for ntidirrhoel mediction were ssessed t the end of follow-up Sttisticl nlysis Quntittive dt were reported s the medin nd rnge, nd qulittive dt were reported s the number of ptients [percentge of ptients]. Normlly distributed quntittive dt were nlysed with Student s t test, nd the Mnn-Whitney test ws used otherwise. Qulittive dt were compred using Person s χ 2 test or Fisher s exct test, s pproprite. Multivrite nlysis of postopertive morbidity risk fctors fter two- nd three-stge IPAA ws performed ccording to logistic regression model, which included ll vribles with p-vlue of less thn 0.2 in univrite nlysis. All tests were two-sided, with level of significnce set t p-vlue of less thn All nlyses were performed using the GrphPd Prism softwre [CA, USA] nd the Sttisticl Pckge for the Socil Sciences [SPSS] softwre [SPSS Inc., version 22.0, Chicgo, IL, USA]. This study ws conducted ccording to the ethicl stndrds of the Committee on Humn Experimenttion of our institution, nd reported ccording to the Strengthening the Reporting of Observtionl Studies in Epidemiology [STROBE] guidelines Results 3.1. Ptient chrcteristics From 2000 to 2015, 202 ptients with IBD underwent lproscopic IPAA in our institution, but 185 ptients were definitively included [Figure 1]. In ll, 82 ptients underwent two-stge procedure [Group A] [44%] nd 103 ptients three-stge procedure [Group B] [56%]. Ptients chrcteristics re detiled in Tble 1. Ptients from the two groups did not show ny difference regrding gender, body mss index, nesthesiology grde, or comorbidities. However, ptients from Group B were younger (39 [15 78] vs 43 [16 74] yers, p = 0.019) nd presented more frequently with Crohn s disese [n = 16, 16%, vs n = 4, 5%, p < ] thn those from Group A. Moreover, ptients from Group B were more frequently operted not electively, for n cute colitis, [n = 38, 37% vs n = 1, 1%, p < ] nd in erly disese stge (4.7 [0.2 30] vs 10 [0 41] yers, p < ) thn those from Group A. The subgroup of 38 ptients presenting with cute colitis in Group B included: clinicl nd endoscopic cute colitis [n = 28], sepsis [n = 6], colonic perfortion [n = 3], nd toxic megcolon [n = 1]. No cse of hemorrhge ws observed. Totl mesorectl excision ws performed for cncer or dysplsi in 30 ptients in Group A [37%] nd 6 ptients in Group B [6%; p < ] Opertive results Cumultive medin opertive time nd hospitl sty were significntly longer in Group B (580 [ ] min, nd 19 [13 60] dys, respectively) thn in Group A (290 [ ] min, nd 10 [7 47] dys; p < ), s shown in Tble 2. There ws no significnt difference regrding rtes of conversion into lprotomy nd of blood trnsfusion, type of nstomosis, or presence of pelvic closed suction drin. Overll morbidity did not differ between groups: 51% in Group A nd 53% in Group B [p = 0.88]. No significnt difference between groups ws noted for surgicl, medicl, or mjor morbidity rtes. However, ptients from Group B presented more frequently defunctioning ileostomy-relted complictions thn those from Group A [n = 9 vs 0, p = 0.006]: peristoml bscess [n = 6], bleeding [n = 2], or dis-insertion [n = 1] of ileostomy. Preopertive steroid tretment during the pst 3 months ws the only risk fctor for postopertive morbidity [odds rtio = 4.9, confidence intervl 95% , p = 0.006], wheres the two- or three-stge pproch ws not ssocited with postopertive morbidity [odds rtio = 0.8, confidence intervl 95% = , p = 0.691]. No significnt difference ws noted between groups regrding stom closure rtes [74/75, 99% vs 76/81, 94%, p = 0.21] nd medin time for stom closure (2.3 [ ] vs 2.2 [ ] months, p = 0.32). No difference ws noted between groups regrding complictions from the closure of the diverting stom: nstomotic lekge occurred nd required surgery in two nd three ptients from Group A [3%] nd Group B [4%], respectively [p = 0.67]. Lproscopic IPAA n = 202 ptients Exclusion criteri n=17 - Previous subtotl colectomy with ileo-rectl nstomosis (n=12) - Incomplete first stge (n=3) - No temporry fcl diversion (n=2) Included ptients n=185 Two-stge IPAA (Group A) n=82 (44%) Three-stge IPAA (Group B) n=103 (56%) Figure 1. Flow chrt of ptients undergoing totl coloproctectomy with ilel pouch-nl nstomosis [IPAA].

4 Two- vs Three-stge Ilel Pouch-nl Anstomosis 901 Tble 1. Chrcteristics of 185 ptients undergoing restortive proctocolectomy with ilel pouch-nl nstomosis for inflmmtory bowel disese. Group A Group B p-vlue two-stge three-stge n = 82 n = 103 Gender 0.67 Mle 46 [56] 61 [59] Femle 36 [44] 42 [41] Age [yers] 43 [16 74] b 39 [15 78] Nutritionl sttus BMI c 23 [15 32] 22 [14 31] 0.41 Weight loss > 10%* 9/75 [12] 20/88 [23] 0.09 Albumin [g/l]** 33 [12 49] b 29.5 [6 46] 0.14 Poor nutritionl sttus d 27/49 [55] 47/69 [68] 0.18 ASA grde e * 0.51 I 17/70 [24] 14/83 [17] II 49/70 [70] 63/83 [76] III 4/70 [6] 6/83 [7] Dibetes mellitus 5 [6] 4 [4] 0.51 Active smoker 8 [10] 11 [11] 0.81 Pst surgicl history 22 [27] 15 [15] 0.06 Ulcertive colitis 77 [94] 87 [84] Crohn s disese 4 [5] 16 [16] Undetermined colitis 1 [1] Previous durtion of symptoms [yers] 10 [0 41] b 4.7 [0.2 30] < Recent preopertive tretment f * Steroids 36/58 [62] 50/82 [61] ASA 30/57 [53] 43/77 [56] 0.72 Anti-TNFα 30/55 [55] 50/72 [69] 0.09 Immunomodultors g 24/69 [35] 40/84 [48] 0.14 Min indiction for surgery < Filure of medicl tretment 51 [62] 59 [57] Acute colitis 1 [1] 38 [37] Dysplsi 19 [23] 5 [5] Cncer 11 [14] 1 [1] Elective surgery 82 [100] 65 [63] < Number of ptients [percentge]; b medin [rnge]; c body mss index; d BMI < 18.5, weight loss > 10%, or lbumin < 30 g/l; e Americn Society of Anesthesiology grde; f in the pst 3 months; g includes zthioprine, methotrexte nd ciclosporin; 5-ASA, 5-minoslicylic cid; TNF, tumour necrosis fctor. *Results from vilble dt only; **results from 37 [Group A] nd 62 [Group B] ptients; p < 0.05 ws considered significnt [in bold] Long-term results After medin follow-up of 2.4 [0.1 11] yers in Group A nd 3 [0.3 14] yers in Group B, long-term morbidity rte ws similr between groups [Tble 3]. Rtes of redoing IPAA for filed nstomosis were similr between groups: 1% [n = 1] in Group A vs 5% [n = 5] in Group B [p = 0.23]. Regrding functionl results, no significnt difference ws observed between groups concerning medin number of stools per dy nd night, rtes of fecl incontinence, or use of ntidirrhoel drugs. 4. Discussion Our study suggested tht postopertive overll morbidity ws similr between two- nd three-stge lproscopic IPAA for IBD ptients. This result ws observed despite higher rte of non-elective opertion for cute colitis in ptients with three-stge IPAA, suggesting ptients t higher risk of postopertive morbidity. For this reson, we believe tht two-stge IPAA must be reserved for elective low-risk ptients without recent steroids or nti-tnf therpy, nd without ongoing cute or severe colitis. In ll the other ptients [56% in the present study], nd in opposition to recent series 3, we consider tht lproscopic subtotl colectomy followed by lproscopic completion proctectomy nd IPAA remins the sfer option in IBD ptients. IPAA cn be performed in either two or three stges, with no consensus bout the indictions nd dvntges of the two pproches. The two-stge pproch is often preferred, especilly in young ctive ptients, becuse of obvious dvntges such s decresed number of procedures under generl nesthesi, shorter cumultive hospitl sty, reduced totl costs, 23 nd probbly fster recovery. 15 On the other hnd, three-stge IPAA is preferred in high-risk ptients [with poor nutritionl sttus nd/or under high dose of steroids or nti-tnf, or with cute colitis] 24 nd in those with suspicion of Crohn s disese for which the pthologicl exmintion of the subtotl colectomy specimen cn help to decide for the next opertion [between ileorectl nstomosis nd IPAA]. 17,25 Beside these two stndrd pproches, two other procedures hve been suggested but re not to dte performed routinely in the mjority of centres. First, few uthors hve proposed onestge IPAA [without diverting ileostomy] in selected ptients with ulcertive colitis. 26,27,28 Even if this presented some theoreticl

5 902 D. Mège et l. Tble 2. Opertive findings nd postopertive morbidity in 185 ptients undergoing restortive proctocolectomy with ilel pouch-nl nstomosis for inflmmtory bowel diseses. Group B two-stge three-stge n = 82 n = 103 p-vlue Opertive findings Conversion into lprotomy 1 [1] 1 [1] 1.00 Anstomosis 0.38 Hnd-sewn 1 [1] 4 [4] Stpled mechnicl 81 [99] 99 [96] Pelvic closed suction drin 78 [95] 101 [98] 0.41 Blood trnsfusion* 6/62 [10] 6/78 [8] 0.77 Cumultive opertive time [min]** c 290 [ ] b 580 [ ] < Cumultive morbidity 42 [51] 55 [53] 0.88 Surgicl morbidity 28 [34] 26 [25] 0.19 Anstomotic lekge Ileosigmoidostomy-relted complictions Ileostomy-relted complictions Wound complictions Pouch hemorrhge Intr-bdominl bleeding Ileus c Medicl morbidity 20 [24] 24 [23] 1.00 Urinry infection Venous thromboembolism d Electrolytic disorder Others e Clvien-Dindo clssifiction 0.66 III 30 [71] 36 [65] III-IV 12 [29] 19 [35] Unplnned reopertion 6 [7] 13 [13] 0.33 Cumultive length of sty [dys] 10 [7 47] b 19 [13 60] < Number of ptients [percentge]; b medin [rnge]; c ileus or smll bowel obstruction defined by bdominl distension nd pin, nd vomiting in the postopertive period; d concerned pulmonry embolism or portl vein thrombosis; e concerned cute urinry obstruction, drenl insufficiency, pulmonry infection, troubles of crdic rhythm, scites, sepsis, or lymphngitis. *Results from vilble dt; **results from 75 [Group A] nd 84 [Group B] ptients; p < 0.05 ws considered s significnt [in bold]. dvntges, such s bsence of stom-relted complictions, shorter overll hospitl sty, nd less long-term risk of smll bowel obstruction, it exposes the ptient to possible pelvic sepsis due to nstomotic lekge, with the potentil risk of re-opertion with secondry ileostomy. A met-nlysis highlighted n incresed rte of nstomotic lekge in the non-diverted group, rising some concerns bout this strtegy. 29 Second, more recently some uthors proposed two-stge modified IPAA bsed on initil subtotl colectomy, followed by completed proctectomy nd IPAA without defunctioning ileostomy. This pproch llowed reduction of length of sty nd overll costs, with similr morbidity nd functionl results compred with the stndrd three-stge pproch. However, very few dt re vilble to dte on twostge modified IPAA, nd it seems tht it ws proposed in selected low-risk ptients. 30 Lproscopic pproch is more nd more used for two- nd three-stge IPAA. We nd others hve suggested tht it reduced significntly the overll length of sty of three-stge IPAA observed fter open surgery, 14 with trend towrds lower postopertive morbidity. 6,31 The benefit of the lproscopic pproch for subtotl colectomy in cute colitis ws recently demonstrted by met-nlysis, 12 with significntly reduced wound infection nd intr-bdominl bscess rtes, nd shorter hospitl sty. Concerning IPAA, two studies with multivrite nlysis hve observed tht lproscopy significntly reduced both minor nd mjor postopertive morbidity rtes. 6,31 All these short-term benefits were ssocited with long-term reduction of dhesions 32 nd incresed fertility rtes in young women, s we nd others reported recently. 7,8 For ll these resons, the lproscopic pproch is becoming the stndrd pproch for IPAA in IBD ptients. 4 To dte, there is no rndomized tril concerning two-stge vs three-stge IPAA, nd only five heterogeneous series with conflicting results hve been published so fr. 3,15,16,17,18 Indictions for IPAA, rtes of two- nd three-stge IPAA, nd use of lproscopy were different between series. In the most recent series, 3 including 144 ptients with ulcertive colitis, outcomes were similr between two- nd three-stge IPAA. The uthors concluded tht steroid use nd nti-tnf therpy lone do not justify the choice of three-stge IPAA, s long s the opertion is performed by highvolume IBD surgeon. First however, severl studies hve clerly demonstrted tht recent high-dose steroid therpy 24,33,34 nd nti- TNF gents 35,36,37,38 incresed the risk of pelvic sepsis fter IPAA. Second, 80% of ptients were operted on using the two-stge pproch [by 10 different surgeons] 3 suggesting possible bis nd bsence of stndrdised procedures; nd less thn 20% of ptients underwent the lproscopic pproch. In the present study, ll the ptients were operted by only two colorectl surgeons, with

6 Two- vs Three-stge Ilel Pouch-nl Anstomosis 903 Tble 3. Long-term results in 185 ptients undergoing restortive proctocolectomy with ilel pouch-nl nstomosis for inflmmtory bowel diseses. Group A Group B p-vlue two-stge three-stge n = 82 n = 103 Follow-up [yers] 2.4 [0.1 11] 3 [ ] 0.08 Long-term results Surgicl morbidity b 11 [13] c 22 [21] 0.18 Anstomotic stenosis Incisionl herni Smll bowel obstruction Reopertion d 9 [11] 19 [18] 0.21 Pouchitis 14 [17] 19 [18] 0.85 Definitive stom 3 [4] 7 [7] 0.51 Functionl results Stools per dy** 5.5 [1.5 15] 5.5 [1 20] 0.76 Stools per night** 0 [0 6] 0 [0 5] 0.53 Fecl incontinence* 9/58 [16] 15/75 [20] 0.65 Antidirrhoel drug* 26/47 [55] 20/50 [40] 0.15 Medin [rnge]; b some ptients presented with severl complictions; c number of ptients [percentge]; d for ny reson. * Results from vilble dt; **results from 58 [Group A] nd 75 [Group B] ptients; p < 0.05 ws considered s significnt. loop ileostomy. At this site, there is thus fril wll nd heling difficulties. Although this study is limited by its retrospective nture, we hve tried to minimise the selection bis by including ll ptients with IBD who underwent lproscopic IPAA in our institution. The tendency of more incisionl herni in Group B thn in Group A could become significnt in wider smple. In conclusion, low risk of pelvic sepsis, nd good or cceptble function nd qulity of life is tody much more importnt thn the number of procedures for IPAA. Becuse pelvic sepsis nd nstomotic lekge re known to lter long-term functionl results fter IPAA, by nstomotic stenosis nd/or pouch sclerosis, nd expose the ptient to higher risk of ultimte pouch filure, we consider tht ny sitution exposing the ptient to potentil higher risk of pelvic sepsis fter IPAA must fvour three-stge insted of two-stge IPAA. It included for us ll the ptients with cute colitis refrctory to intensive medicl therpy, ptients under recent nd high dose of steroids, nd ptients recently treted nti-tnf gents. For ll these situtions, which represent to dte pproximtely hlf of our ptients, lproscopic three-stge IPAA continues to be our preferred option. Conflict of Interest None. stndrdised lproscopic IPAA in 100% of cses. 5,11 Similr conclusions in fvour of two-stge IPAA were lso reched in n older series including 871 ptients with ulcertive colitis, ll operted by open surgery with 89% of two-stge IPAA, nd without ny nti- TNF pre-tretment. 16 All the other three studies 15,17,18 compring two- nd three-stge IPAA were more in fvour of three-stge in high risk ptients, with significntly lower overll morbidity, pelvic sepsis, nd ileus rtes in one study. 17 A similr nstomotic lek rte between two- nd three-stge IPAA ws observed in the two other series despite ptients t higher risk of complictions fter threestge IPAA. 15,18 Although no comprison ws performed between two- nd three-stge IPAA in lrge series of 588 ptients, Gu et l. reported tht preopertive nti-tnf tretment ws significntly ssocited with pelvic sepsis in the cse of the two-stge procedure, wheres this ssocition ws not observed fter the three-stge procedure. Such result indicte three-stge IPAA in cse of preopertive nti-tnf tretment. 37 Conversely, Lu et l. reported in prospective series on surgicl mngement of IBD, tht there ws no significnt difference in dverse postopertive outcomes between the detectble nd undetectble serum nti-tnfα drug level groups in cses of ulcertive colitis. When two- nd three-stge IPAA were nlysed seprtely to stndrdise the results ccording to the complexity of ulcertive colitis surgery performed, no significnt difference ws observed. 38 No definitive conclusion cn be reched from these five previous comprtive studies. Finlly, the present study is the first to compre two- vs three-stge with 100% of lproscopic IPAA in IBD ptients. By reducing not only overll length of sty, postopertive morbidity, nd dhesions, but lso the severity of the opertions, we believe tht lproscopy tody hs modified the debte between two- nd three-stge open IPAA. Furthermore, ptients with the three-stge procedure hd more stom complictions thn those in two-stge IPAA, probbly becuse the double-end ileostomy nd sigmoidostomy is performed t the sme site of the defunctioning Author Contributions DM: cquisition of dt, drfting the rticle, nlysis nd interprettion of dt. MNF: cquisition of dt, nlysis nd interprettion of dt. GM: nlysis nd interprettion of dt. LM: nlysis nd interprettion of dt. YP: concept nd design of the study, drfting the rticle, pprovl of the finl version. References 1. Melton GB, Kirn RP, Fzio VW et l. Do preopertive fctors predict subsequent dignosis of Crohn s disese fter ilel pouch-nl nstomosis for ulcertive or indeterminte colitis? Colorectl Dis 2010;12: Pnis Y, Pouprd B, Nemeth J, Lvergne A, Hutefeuille P, Vlleur P. Ilel pouch/nl nstomosis for Crohn s disese. Lncet 1996;347: Hicks CW, Hodin RA, Bordeinou L. Possible overuse of three-stge procedures for ctive ulcertive colitis. JAMA Surg 2013;148: Mggiori L, Pnis Y. 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