PillCam Colon 2 capsule in patients unable or unwilling to undergo colonoscopy

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1 Online Submissions: doi: /wjge.v5.i World J Gstrointest Endosc 2013 November 16; 5(11): ISSN (online) 2013 Bishideng Publishing Group Co., Limited. All rights reserved. BRIEF ARTICLE PillCm Colon 2 cpsule in ptients unble or unwilling to undergo colonoscopy Lucin Negrenu, Ruxndr Bbiuc, Andree Bengus, Roxn Sdgurschi Lucin Negrenu, Ruxndr Bbiuc, Andree Bengus, Roxn Sdgurschi, Internl Medicine 2 Gstroenterology Deprtment, University Hospitl, Crol Dvil University of Medicine Buchrest, Buchrest, Romni Author contributions: All uthors prticipted in the study; Negrenu L designed, wrote the rticle nd mde corrections; Sdgurschi R helped with rticle redction nd corrections. Supported by ESGE GIVEN Reserch Grnt 2010 Correspondence to: Lucin Negrenu, MD, PhD, Internl Medicine 2 Gstroenterology Deprtment, University Hospitl, Crol Dvil University of Medicine Buchrest, 169 spliul Independentei Street, sector 5, Buchrest, Romni. negrenu_99@yhoo.com Telephone: Fx: Received: June 29, 2013 Revised: September 5, 2013 Accepted: October 11, 2013 Published online: November 16, 2013 Abstrct AIM: To ssess the fesibility, ccurcy nd cceptbility of PillCm Colon 2 in detection of significnt lesions in colorectl cncer risk ptients, unble or unwilling to perform colonoscopy. METHODS: This is prospective, single center study using the second genertion of PillCm Colon cpsule. In ll ptients the reders were instructed to review the entire colon cpsule endoscopy (CCE) exmintion using Rpid 7 softwre nd dditionlly to note significnt extr-colonic findings. Colonic significnt findings were described ccording to Europen Society of Gstrointestinl Endoscopy guidelines. CCE procedure completion rte, level of bowel preprtion nd rte of dverse events were ssessed. RESULTS: A totl of 70 ptients t risk of colorectl cncer were enrolled in the study. In three ptients the procedure filed becuse the cpsule ws not functioning when entered the colon. PillCm Colon 2 showed positive findings in 23 (34%, 95%CI: 21.6%-44.1%) of the remining 67 ptients. Six ptients were dignosed with tumors: 4 with colon cncers, 1 with gstric cncer nd 1 with smll bowel cncer. The cpsule findings were confirmed fter surgery in ll these ptients. The cpsule excretion rte in twelve hours ws 77% with 54 ptients hving complete exmintion. The rectum ws not explored during CCE procedure, in 16 ptients (23%, 95%CI: 13.7%-34.1%). Every ptient ccepted CCE s n lterntive explortion tool nd 65/70 (93%) greed to hve nother future control by CCE. No complictions were reported during or fter CCE exmintion. CONCLUSION: PillCm Colon 2 cpsule ws effective in detecting significnt lesions nd might be considered n dequte lterntive dignostic tool in ptients unble or unwilling to undergo colonoscopy Bishideng Publishing Group Co., Limited. All rights reserved. Key words: Colon cncer; Colonoscopy filure; Colonoscopy refuse; Colon cpsule; Pillcm Colon 2 Core tip: This is n importnt rticle on the second genertion colon cpsule endoscopy. It shows tht it hs high dignostic yield in n enriched popultion tht hve hd incomplete colonoscopy or refused colonoscopy. We lso dignosed significnt extrcolonic lesions. The method hd high cceptbility mong ptients nd we did not encounter ny complictions. Negrenu L, Bbiuc R, Bengus A, Sdgurschi R. PillCm Colon 2 cpsule in ptients unble or unwilling to undergo colonoscopy. World J Gstrointest Endosc 2013; 5(11): Avilble from: URL: htm DOI: INTRODUCTION Colorectl cncer (CRC) is the second most common cncer nd second most common cuse of cncer-relted 559 November 16, 2013 Volume 5 Issue 11

2 deths in Europe. CRC screening hs been proven to reduce disese-specific mortlity [1]. The choice of screening test tkes into considertion prmeters such s ptient ge nd the presence of different risk fctors for the development of CRC. Severl Europen countries employ ntionl screening progrms. They rely lmost exclusively on stool tests, with colonoscopy used s n djunct in some countries. Colonoscopy hs been shown to reduce colorectl cncer risk. Its incresed use in the popultion ged 50 yers nd older in the United Sttes since the 1980s is the reson for decresing CRC incidence rtes, prticulrly in the sigmoid, colon lthough some environmentl fctors my lso hve contributed to the decresing risk [2]. A prediction for 2012 expects decline in mortlity from colorectl cncer of 7% in men nd 11% in women in the Europen Union compred with 2007 minly due to the screening progrms [3]. Nevertheless the uptke of ptients in the screening progrms is disppointingly low. The degree of cceptnce of colonoscopy is low becuse it is perceived by some ptients/physicins s invsive nd pinful nd with degree of complictions/risks. Another drwbck is the rte of filed colonoscopic exmintions. The cecl intubtion filure rte is up to 20% of colonoscopies in clinicl prctice [4]. No guideline exists for these ptients but severl options re being used with different success rtes. Computed tomogrphic colonogrphy (CTC) is useful option nd seems supported by recent studies [5]. Colon cpsule endoscopy (CCE) PillCm Colon ws developed by Given Imging especilly for incresing the cceptbility nd sfety of colorectl exmintion. Although bowel preprtion similr to colonoscopy is necessry, this technique requires no intubtion, insuffltion or sedtion nd hs miniml compliction rtes/ risks [6,7]. A second-genertion, improved, CCE system (Pill- Cm Colon 2) ws developed to increse sensitivity for colorectl polyp detection compred with the first-genertion system. A recent study using second-genertion colon cpsule showed higher sensitivity thn the first genertion, of lmost 90% for detection of ptients with significnt colonic lesions [8]. Recently the Europen Society of Gstrointestinl Endoscopy published n updted nd extensive guideline regrding the current sttus of cpsule endoscopy. It gives cler perspective bout the indictions, bowel preprtion, reporting nd level of evidence [9]. According to these guidelines, CCE is fesible nd sfe nd ppers to be n ccurte screening tool when used in verge-risk individuls. A CCE bsed screening my be cost-effective if it increses uptke compred with colonoscopy. In high risk ptients (lrm symptoms or signs, fmily or personl history of CRC), which re t incresed risk of dvnced colorectl neoplsi or cncer, colonoscopy should be the first choice. However, in ptients for whom colonoscopy is inpproprite or not possible, the use of CCE could be discussed with the ptient [9]. Study im We conducted pilot tril to sses the fesibility, ccurcy nd cceptbility of PillCm Colon 2 in detection of significnt lesions in ptients t risk of CRC which were unble or unwilling to perform colonoscopy. Following recent Europen Society of Gstrointestinl Endoscopy (ESGE) cpsule endoscopy guideline, significnt colorectl lesion tht requires colonoscopy follow-up ws considered to be colorectl polyp > 6 mm or presence of t lest 3 colonic polyps [9]. End points Since we could not compre colon cpsule endoscopy CCE to the gold stndrd (colonoscopy) we introduced new end point of positive exmintion: the dignostic utility index (findings directly explining symptoms or requiring specific tretment in symptomtic ptients). Although using this end point even norml exmintion cn be considered successful for certin ptient if it is importnt for the clinicl decision nd follow up, we decided to consider significnt the cpsule findings tht required medicl or surgicl tretment. Also ptient follow up of one yer ws mndtory. CCE procedure completion rte level of bowel preprtion nd rte of dverse events were lso ssessed. MATERIALS AND METHODS Ptients A totl of 70 ptients of men ge 58.3 yers (rnge 29 to 87) were enrolled in this prospective, single center study. Indictions Inclusion criteri were s follows: (1) ptients t risk for CRC unble to undergo the colonoscopic exmintion becuse of the nesthetic risk nd co-morbidities; (2) ptients t risk for CRC who refused colonoscopy. We considered s ptients t risk for CRC, ptients with personl or fmily history of denoms or colorectl cncer, but lso with digestive symptoms such s bleeding, recent bowel hbits chnge, weight loss, nemi, bdominl pin, positive fecl occult blood test nd suspect imgingbdominl ultrsound, computed tomogrphy (CT)/positron emission CT scn were included in the study. Mjority of ptients unwilling to undergo the colonoscopic exmintion hve hd negtive experience with prior colonoscopy (either n incomplete or filed colonoscopy becuse of the bdominl discomfort). The Pill- Cm Colon 2 exmintion ws proposed s n lterntive tool to explore the colon to these ptients. Exclusion criteri comprised: (1) ptients with pcemkers; (2) ptients with suspected digestive stenosis or intestinl occlusion; nd (3) ptients with dysphgi or swllowing disorders. Ethicl considertions The study ws pproved by the Ethics Committee of the University Hospitl of Buchrest nd ptients signed 560 November 16, 2013 Volume 5 Issue 11

3 23 (33%) pts with relevnt lesions 19 (28%) pts with non-relevnt lesions Number included: 70 Number nlyzed: (37%) pts w/o findings 3 did not rech the colon (4%), however 1 relevnt SB finding ws detected (rdition entertis) 20 with 55 polyps 6 with cncer No f/u 17 (23%) therpeutic interventions Figure 1 In ll ptients the reders were instructed to review the entire colon cpsule endoscopy exmintion nd dditionlly significnt extr-colonic findings. All ptiets hd t lest one yer follow up. The cse no f/u will disper. n informed consent for the investigtion. Enrollment strted in Februry PillCm Colon 2 procedure The second genertion PillCm Colon 2 cpsule nd Rpid reder 7 softwre were used in this study. The Pillcm Colon 2 cpsule is slightly longer thn the previous genertion with 11.6 mm 31.5 mm in size. It hs been designed to work for t lest 10 h nd it hs vrible frme rte (from 4 to 35 frmes/second in order to correctly visulize the mucos when ccelerted peristlsis). The ngle of view ws incresed to 172 degrees in both cpsule lenses, thus covering lmost 360 degrees of the colonic surfce. A new smller nd more ergonomic dt recorder with liquid crystl disply llowing rel time viewing ws developed. It permits bidirectionl communiction with the cpsule nd lso is friendlier nd esier to use by the ptient providing utomtic visul nd udio signls for procedure ctivities (boost dministrtion). All the investigtors reding the cpsule videos hd extensive experience in digestive endoscopy nd they hd previous experience using the smll-bowel cpsule. Before the study strt trining session ws orgnized by Given Imging. This 2-d trining session included severl hours of sessions ddressing different issues s preprtion, procedure nd softwre utiliztion. It ws followed by self-ssessment test consisting of reding ten colon cpsule videos. The first three exmintions in the study were performed under supervision from Given Imging. Colon preprtion nd clenliness estimtion Prticipting ptients received written nd orl explntions of colonic preprtion detils. The preprtion consisted in low-residue diet strting 48 h before investigtion nd cler liquid diet 24 h before ingestion. A 4 L of split-dose polyethylene glycol (PEG) Fortrns (Mcrogol 4000, Ibsen, Frnce) prep ws dministered in the evening nd 2 h prior to cpsule ingestion. Since in Romni orl sodium phosphte is not vilble, PEG ws used s booster. Upon cpsule exit from the stomch first liter of PEG ws dministered nd second boost of one liter of PEG ws dministered if the cpsule ws not excreted 3 h fter the first one. Colon clenliness ws grded using two point scle. This scle ws development of the originl 4-point scle used in previous studies nd grdes preprtion s indequte (poor or fir on the 4-point scle) or dequte (good or excellent on the 4-point scle) [10]. The clenliness ws ssessed in ech of the five colon segments (cecum, right colon, trnsverse, left colon nd rectum) nd then generl estimte of the entire colon ws mde. RESULTS In ll ptients the reders were instructed to review the entire CCE exmintion nd dditionlly significnt extr-colonic findings (Figure 1). Indictions The min indiction for initil colonoscopy or for the otherwise contrindicted/refused colonoscopy hd been: 35 symptomtic ptients (bnorml trnsit 8, bdominl pin 4, nemi or overt bleeding 22, weight loss 1), 29 verge nd high risk colorectl cncer screening ptients (fmilil 21 or personl history of polyps or cncer 5, cromegly 1, long stnding inflmmtory bowel disese 1, screening 1) nd 6 ptients with bnorml imging or tumor mrkers. The indictions for referrl of the ptients re detiled in the Tble 1. The indiction of cpsule exmintion ws: refusl of colonoscopy in 37 ptients, previous incomplete colonoscopy (mostly technicl filures of initil colonoscopy) in 30 ptients or unble to perform colonoscopy (the exmintion risks-crdiovsculr or nesthetic were considered excessive by their own physicins) in 3 ptients. Findings In three ptients the procedure filed becuse the cpsule ws not functioning when it entered the colon. In the remining 67 ptients significnt dignosis ws mde 561 November 16, 2013 Volume 5 Issue 11

4 Tble 1 The min indiction for initil colonoscopy or for the otherwise contrindicted/refused colonoscopy, the indictions for referrl of the ptients Ptient Sex Age Reson Indiction for CCE Findings Completion Preprtion 1 Femle 85 Suspect CT Refuse 3 pedunculted polyps in the descending colon 7-9 c mm, voluminous diverticul in the sigmoid 2 Femle 45 Trnsit troubles (dirrhe), fmily Filure Diverticul c history 3 Mle 76 Anemi Filure 3 polyps 3-8 mm left colon c 4 Mle 39 Fmily history Refuse 4 polyps 3-8 mm left colon c 5 Mle 52 Personl history of colorectl polyps Refuse 4 polyps 4-8 mm left colon c 6 Mle 60 Abdominl pin weight loss Filure 6 mm polyp cecum c 7 Femle 69 Trnsit troubles Refuse 6 mm polyp right colon, diverticul c 8 Femle 57 Personl history of polyps Filure 6 polyps 3-5 mm 2 trnsverse 4 left colon, diverticul c 9 Mle 80 Anemi severe, weight loss Filure Angioms c 10 Mle 53 Trnsit troubles Refuse Diverticul c 11 Femle 61 Fmily history Filure Diverticul c 12 Femle 58 Trnsit troubles (dirrhe) Refuse Diverticul c 13 Mle 54 Fmily history (mother, unt nd Refuse Diverticul c uncle with CRC) 14 Femle 65 Abdominl pin history of resected Filure Diverticul c trnsverse cncer history of urinry bldder cncer 15 Mle 39 Fmily history Refuse Diverticul c 16 Femle 56 Fmily history (fther with CC t 82) Refuse Diverticul c polyps 17 Mle 58 Personl history of cncer,colectomy Refuse Diverticul c 18 Mle 31 Fmily history( fther CRC t 46) Refuse Diverticul c n 19 Mle 62 Screening Filure Diverticul peridiverticulr inflmmtion smll erosion c on the IC vlve 3 mm polyp in the cecum 20 Mle 69 Anemi weight loss Refuse Diverticul polyp 5 mm in the descedent colon internl c hemorrhoids 21 Femle 49 Trnsit troubles Refuse Diverticul smll polyp 3 mm left colon some petechie c n on the descendent colon 22 Mle 75 Trnsit troubles Filure Diverticul,16 mm ulcerted submucosl mss in the c sigmoid 23 Mle 59 Fmily history Refuse Diverticul, 4 mm polyp sessile left colon c n 24 Mle 64 Fmily history CRC Filure Norml c resection of polyps 25 Femle 60 Fmily history (mother with rectl Refuse Norml c cncer) 26 Femle 55 Suspect mss on CT Refuse Norml c 27 Femle 77 Anemi Filure Norml c 28 Mle 64 Anemi weight loss Filure Norml c 29 Femle 60 Fmily history Refuse Norml c 30 Femle 56 Trnsit troubles Refuse Norml c 31 mle 36 Fmily history, trnsit troubles Refuse Norml c 32 Femle 39 Fmily history Filure Norml c 33 Femle 29 Anemi, grndmother with colon Refuse Norml c cncer constiption 34 Femle 44 Anemi Refuse Norml c 35 Mle 59 Fmily history (colorectl cncer in Filure Norml c the mother t erly ge) bdominl pin 36 Femle 39 Acromegly Refuse Norml c 37 Femle 42 Tumorl mrkers Filure Norml c 38 Femle 59 Anemi weight loss dirrhe suspect CT Crdiologist choice Norml c 39 Femle 49 Abdominl pin Refuse Norml c 40 Mle 59 Trnsit troubles (dirrhe), fmily Refuse Norml c n history 41 Mle 42 Fmily history Refuse Norml c n 42 Mle 51 Fmily history Filure Norml c n 43 Femle 43 suspect pet scn, ovrin cncer Filure Norml c n 44 Mle 34 Fmily history (mother nd fther Refuse Norml c n operted with ccr) 45 Femle 66 Tumorl mrkers Filure Norml c n 46 Femle 65 Fmily history Filure Norml c n 562 November 16, 2013 Volume 5 Issue 11

5 47 Mle 68 Bleeding, personl history of polyps Refuse Norml c n 48 Femle 65 Personl history (colon resection) Refuse Norml resected colon c 49 Femle 41 Anemi, fh Refuse Polip cecum < 5 mm c 50 Mle 65 Long stnding uc, renl trnsplnttion Filure Ulcertive colitis, pseudopolyps c 51 Femle 75 Anemi, suspect ultrsound exm Refuse Smll bowel tumor mm, 6 mm polyp descending c 52 Femle 56 Anemi weight loss Filure Ulcerted tumor in the cecum c 53 Femle 65 Anemi Filure Ulcerted tumor in the cecum c 54 Mle 45 Abdominl pin Refuse Ulcertion on the ileon nd ilel vlve, Crohn's? c diverticul 55 Femle 78 Anemi Filure 10 right trnsverse polyps 4-9 mm, ngioms, left i n side not seen, diverticul 56 Femle 45 Fmily history Filure 13 mm pedunculted polyp trnsverse colon, diverticul i n 57 Mle 77 Anemi weight loss crdiologist 3 polyps 10 mm nd 5 nd 4 mm left colon i n Choice 58 Femle 68 Fmily history Filure 3 polyps 3-4 mm left colon,diverticul i n 59 Femle 84 Personl history (hemicolectomy for right sided cncer) Filure 4 polyps 5-7 mm left colon i 60 Femle 76 Fmily history of CRC ( mother nd brother ) Refuse 7 mm polyp on the ileo-cecl vlve; cecl ngiodysplsi; multiple diverticul in the right nd left colon 61 Femle 87 Suspect CT nd brium enem Filure Angiomtosis i 62 Mle 52 Bleeding, hemtochezi Refuse Diverticul i n 63 Mle 58 Anemi, suspect ct, personl nd Filure gstric cncer, 5 polyps 3-4 mm left side, diverticul i fmily history 64 Mle 75 Weight loss Refuse Norml but cncer discovered fter 3 mo i n 65 Mle 73 Anemi weight loss Refuse Diverticul bttery depleted Ⅰ bttery n 66 Femle 61 Anemi Refuse Cncer Impction on cncer 67 Mle 38 Anemi Filure Cncer two tumors Impction n on cncer 68 Femle 61 Anemi, weight loss, dirrhe Filure Impction on rdition enteritis stenosis Impction on rdition enteritis 69 Mle 60 Fmily history Refuse Impction Retention gstric 70 Mle 65 Anemi melen, Norml endoscopy Crdiologist choice Impction i Retention smll bowel : Adequte; n: Non-dequte; c: Complete; i: Incomplete; CRC: Colorectl cncer; CCE: Colon cpsule endoscopy; CT: Computed tomogrphy. in 23 (34%, 95%CI: 21.6%-44.1%). The significnt lesions reported were: polyps > 6 mm in five ptients, 3 polyps in 10 ptients, multiple colonic ngioms in 2 ptients, colon cncer in 4 ptients, other digestive cncers in 2 ptients, newly discovered Crohn s disese in 1 ptient nd rdition enteritis in nother. A totl of 19 ptients hd insignificnt lesions (17 with diverticulosis, 1 with ulcertive colitis nd inflmmtory pseudopolyps nd 1 with < 6 mm polyp). Twenty five ptients hd no findings with norml colonic exmintions. Fifty-five colonic polyps were identified by CCE in twenty ptients. In the 15 ptients with polyps over 6 mm or more thn 3 polyps we identified 50 polyps with medin size of 5.8 mm (rnge 3 to 13 mm) nd medin number of 3.5 polyp/ptient (rnge 1 to 10), with loctions in the right colon (3), trnsverse colon (13), left colon nd rectum (34). We found 5 polyps < 6 mm in five ptients (2 polyps locted in the right colon nd 3 in the left colon). Four ptients hd colon tumors detected by CCE: (1) ptient with two synchronous lesions in the cecum nd scending colon, (2) ptients with ulcerted cecl tumors (Figure 2A nd B) nd 1 ptient with left ngle stenotic tumor (Figure 2C). Two other digestive tumors were discovered by the CCE exmintion. In one ptient with iron deficiency nemi, suspect CT scn (bdominl mss) nd filure of colonoscopy n ulcerted lesion ws discovered by cpsule in the stomch. An upper endoscopy with biopsies estblished the dignosis of undifferentited gstric cncer (Figure 2D). In nother ptient with nemi nd suspect imging (mss seen on ultrsound) nd refusing colonoscopy n ulcerted tumor in the smll bowel ws visulized t cpsule (Figure 2E). In one of the ptients with cpsule impction in the smll bowel, we mde the dignosis of rdition enteritis which ws considered significnt. For the other two ptients where cpsule did not rech the colon while functioning, no significnt lesions were described in the exmined segments. Preprtion Bowel clenliness ws reported s dequte (good or excellent) in 48 of cses (72%, 95%CI: 60.8%-82.4%) nd indequte (fir or poor) in 19 cses (28%, 95%CI: 17.6%-39.1%). In the three cses where cpsule did not rech the colon we could not nlyze the preprtion. 563 November 16, 2013 Volume 5 Issue 11

6 A 14 Oct 11 B 11 Oct 12 C 21 Mr 12 dvb mc SA PillCm colon 2 PillCm colon 2 PillCm colon 2 D 29 Oct 12 E 12 Oct 11 mb id PillCm colon 2 PillCm colon 2 Figure 2 The results of colon cpsule endoscopy exmintion. A: Cecum tumor-trnsvlvulr vue; B: Ulcerted tumor in the cecum; C: Ulcerted stenosis of the left colon ngle; D: Gstric cncer; E: Smll bowel tumor. Trnsit time nd cpsule egestion The cpsule excretion rte in 12 h ws 77% with 54 ptients hving complete exmintion. The medin colonic trnsit time CTT ws 189 min (rnge 3 to 665 min) with importnt differences between ptients. The rectum ws not explored during CCE procedure, in 16 ptients (23%, 95%CI: 13.7%-34.1%). Of these 16 ptients who did not hve complete cpsule procedure, in 3 ptients (4%) the cpsule did not rech the colon t ll. In 11 cses recording cesed in the left colon nd in 2 it impcted bove tumors of the right nd left colon ngle, respectively. In 9 of these 11 ptients the cpsule indiction ws filure of previous colonoscopy so we considered hving complete colonic exmintion. All ptients but two eliminted the cpsule in the following 48 h. A true cpsule retention (cpsules remining in the digestive trct more thn 14 d nd extrcted during surgicl tretment of the lesions) ws seen only in 2 ptients due to digestive stenosis. First impction occurred in n ilel stenosis relted to rdition enteritis. This ptient ws referred from nother hospitl for suspicion of colon cncer in the descending colon fter filed colonoscopy with impossibility to pss the sigmoid. She hd no symptoms suggestive of digestive stenosis or occlusion but history of irrdition 24 yers go for uterine cncer. The other cse ws n impction in stenotic tumor of the left colonic ngle in ptient referred for nemi nd trnsit troubles nd refusing colonoscopy. In both ptients surgery ws decided bsed on cpsule findings nd ws successful nd without complictions nd relized in the following month. We encountered nother cpsule trnsient impction bove tumorl colonic stenosis in young ptient referred for iron deficiency nemi where two lesions of the cecum nd right colonic ngle were visulized during the exmintion. The ptient eliminted the cpsule in the following dy. He hd surgery fter complete pre opertive check up including colonoscopy nd CT scn which confirmed the two synchronous lesions. Besides the ptient with rdic ilel stenosis, the other two where the cpsules did not rech the colon while working, excreted the fter 48 h without complictions. In one ptient with history of colon cncer in both prents nd refusing colonoscopy the cpsule remined in the stomch during the entire bttery lifetime. He refused n upper endoscopy to push the cpsule. He remined symptomtic during nd fter cpsule pssge. The other ptient ws morbidly obese nd confined to bed nd the cpsule remined in the smll bowel until bttery depletion. Follow up, clinicl decision nd tretment Seventeen ptients (74%) out of the 23 with relevnt lesions dignosed by CCE greed to hve therpeutic intervention. The 4 ptients detected with colon tumors hd successful surgery. Only 2 of them hd colonoscopies before surgery, for the other 2 ptients the surgicl indiction being decided bsed single on CCE results. The cpsule findings were confirmed fter surgery. Dignosis of denocrcinom ws estblished in ll cses nd the tumor loction ws similr to the cpsule findings. 564 November 16, 2013 Volume 5 Issue 11

7 One ptient detected with smll bowel tumor hd surgery fter the CCE nd n ulcerted gist ws removed. For the gstric ulcerted lesion visulized by cpsule, n upper endoscopy with biopsies ws relized. After histologicl confirmtion of undifferentited gstric cncer, the ptient hd subtotl gstric resection. In the two ptients with severe iron deficiency nemi nd multiple hospitliztions for trnsfusions nd where previous colonoscopies filed, the CCE mde the dignosis of multiple ngioms. Before CCE both ptients hd extensive check ups including upper endoscopies, filed colonoscopies, CT scns nd brium contrst enems nd they hve t lest three hospitliztions only in our institution. After CCE repeted sénces of rgon plsm cogultion were relized with gret del of improvement of their nemi. In order to rech the cecum single blloon enteroscope ws used for one ptient nd vrible stiffness colonoscope ws used for the other. Six ptients with relevnt lesions which previously denied colonoscopy ccepted the exmintion fter discussion of the CCE results. Colonoscopy confirmed the findings of the CCE nd polypectomy ws performed in ll cses. In ptient with suspicion of loclly invding cecl tumor on CT scn, the CCE ruled out this dignosis nd showed only three colonic polyps one in the cecum nd two in the descending colon. In this cse the CCE hd n importnt role in the clinicl decision since it ruled out colonic cncer. After creful exmintion of the imging; explortory lprotomy estblished dignosis of bdominl wll srcom ws estblished. She hd surgery soon fterwrds. No colonoscopy for the three left side polyps ws relized. The newly dignosed Crohn s disese ptient hd complete check up nd he is currently under immune modultor therpy. We hd one clinicl filure reveled by the follow up, 4 mo fter CCE. A 76-yer-old ptient with fmily history nd bnorml trnsit who refused colonoscopy hd n incomplete colon exmintion by CCE cused by poor visuliztion due to low complince to the preprtion nd the booster regimen. He refused rectoscopy fter CCE. Since he remined symptomtic he greed to hve rectoscopy which reveled smll ulcerted rectl tumor. This ptient hd successful surgery fter pre opertory rdiotherpy. Six ptients either refused colonoscopy nd polypectomy or decided to postpone the procedure. At the moment they re followed up in our center. Acceptbility The ptients included in the study hd the indiction of colonoscopy tht either filed or ws refused. When offered the lterntive of hving CCE exmintion ll the 70 ptients ccepted it, lthough they were wre tht the preprtion regimen ws more difficult thn for clssic colonoscopy. Moreover the exmintion ws subjectively pprecited by ll ptients s being non invsive nd hrmless nd 65 of them where willing to hve the next surveillnce exm by CCE. Adverse events Cpsule ingestion went smoothly in ll ptients. Although most ptients hd to ingest totl of six liters of PEG (preprtion nd boosters) no electrolyte disturbnces or dverse effects relted to bowel preprtion were recorded. No other side effects relted to cpsule were encountered. Technicl filures We hd one CCE technicl filure due to recorder dysfunction which required nother exmintion. DISCUSSION The existing ntionl CRC screening progrms re fr from perfect due to different issues: lck of universl screening policy despite recommendtions, lck of uniform mesures in ll countries, cost issues. One mjor problem is the disppointingly low number of ptients ccepting the current screening tools. Furthermore is not negligible tht vrible proportion (4%-20%) of ptients will hve n incomplete colonoscopy lthough the rte of completeness is s high s 97% in expert centers [4]. After n incomplete exmintion with stndrd dult colonoscope different pproches re vilble: vrible stiffness colonoscope, use of gstroscope, single or double blloon enteroscopy (vilble in some centers). Chnging the centre or the endoscopist is n lterntive. However first filed colonoscopy is significntly ssocited with lower cecl intubtion rte t further ttempts, prticulrly when stopped in the sigmoid colon [4]. Rdiologicl procedures hve been tested nd they re proposed s potentil screening test in the verge risk popultion [11], for high risk ptients colonoscopy remining the first option. For ptients with colonoscopy filure or contrindiction, rdiologicl imging is n option recommended by current guidelines [11]. The use of double contrst brium enem (DCBE) ws disppointing considering the low sensitivity for polypoid lesions nd denoms, when compred to colonoscopy or CTC [12]. In recent Itlin met-nlysis, DCBE showed sttisticlly lower sensitivity nd specificity thn CTC for detecting colorectl polyps 6 mm, nd its use s n lterntive imging test is pproprite only when CTC is not vilble [12]. Two studies reported vrying results using computed CTC fter filed or n incomplete colonoscopy [13,14], with n estimted sensitivity of 88% for dvnced neoplsi 10 mm. Rdition exposure remins concern despite the evolution of technique nd improvement of exmintion protocols. The cost effectiveness of CTC bsed screening progrm is debtble s the medicl nd economic impct of extr colonic findings remins unknown [15]. We could not mke direct comprison in our popultion of ptients, since CTC is not reimbursed by the Romnin helth system nd its vilbility is very 565 November 16, 2013 Volume 5 Issue 11

8 limited. The current ESGE cpsule endoscopy guidelines tke into considertion the utiliztion of CCE fter filure or refuse of colonoscopy. According to these guidelines, CCE is fesible nd sfe nd ppers to be ccurte when used in verge-risk individuls nd in high risk ptients for whom colonoscopy is inpproprite or not possible. For these ptients the use of CCE could be n lterntive [9]. We report the Pillcm Colon 2 use in high risk ptients unwilling or unble to perform colonoscopy. Therefore we lck the comprison with colonoscopy which is the gold stndrd. The introduction of dignostic utility index nd the creful follow-up of the ptients prtilly solved this issue. Clinicl significnt lesions were seen by Pillcm Colon 2 in 23 ptients out of 67 nlyzed (34%) CCE hd high clinicl impct s endoscopic or surgicl tretment ws proposed in ll these cses bsed on cpsule results nd seventeen ptients (74%) of the 23 with relevnt lesions greed to nd hd therpeutic intervention (Figure 1). Complete colorectl exmintion ws relized by CCE in 54 ptients (77%, 95%CI: 67.3%-86.94%). The rte of complete exmintions observed in our group is lower thn in the study of Spd et l [8] of 88% but much like the findings of Elikim et l [6] who reported cpsule egestion rte of 74% in their first genertion cpsule study. Severl fctors my hve influenced the progression rte: in the bsence of clssic sodium phosphte boosters unvilble on the locl mrket, the use of Mcrogol s booster hs been fctor ffecting the trnsit times. Also our study popultion included ptients with previous difficult colonoscopies or with vrious co-morbidities nd bed confined ptients. The presence of fixed sigmoid loops in ptients with previous colonoscopy filure might hve contributed to slow trnsit times. Also in three ptients with incomplete CCE exmintion, this ws due to impction over significnt lesions (one postrdic stenosis nd two cncers) during the procedure. Compred with CTC, CCE hs the intrinsic dvntge of directly visulizing the colonic mucos. This my be very importnt s cliniclly relevnt lesions like ngiectsis or flt denoms re missed by CTC nd re esily visible in cpsule endoscopy. This is confirmed in our study where cpsule endoscopy estblished the definitive dignosis of multiple ngioms in two ptients who hd previous CT scns nd brium enems in severl occsions. In recently published multicenter (17 hospitls nd privte prctices) study using first genertion Pillcm Colon 1 in ptients with filure or contrindictions to colonoscopy, the CCE showed positive findings in 36 ptients out of 107 nlyzed (dignostic yield 33.6%). The Pillcm Colon 1 ws considered s hving high clinicl impct s in 21% of ptients medicl or surgicl tretment ws proposed. In this study the colon exmintion by CCE ws complete in 83.2% of cses [16]. Our results re comprble. However it is single center study with different study design. Also the clssicl boosts with sodium phosphte where not vilble for our popultion leding to the lower excretion rtes. In our study the cceptbility of the exmintion by CCE ws extremely high. All ptients with previous filed colonoscopy proposed to tke prt in the study ccepted the CCE exmintion. The method ws perceived s non invsive nd hrmless by ll ptients. Moreover the vst mjority of ptients with significnt findings, either filure or refusl of colonoscopy, greed to perform therpeutic gesture (implying colonoscopy) fter the discussion of the CCE findings. The PillCm Colon 2 ppers to be effective for the detection of cliniclly relevnt lesions with gret cceptbility rte, nd it might be considered s useful tool for colorectl imging in ptients unble or unwilling to undergo colonoscopy. Further studies re necessry to vlidte the best pproch to these ptients. The Given Imging Reserch Grnt supports innovtive, originl reserch in Gstroenterology with substntil involvement of cpsule endoscopy nd is wrded yerly by the Europen Society of Gstrointestinl Endoscopy. The project Role of PillCm Colon 2 cpsule in ptients t risk of CRC unble or unwilling to perform colonoscopy ws wrded with the 2010 grnt. The study design, dt nlysis, results nd conclusions of the rticle re exclusively the investigtors work. Given Imging supported the study, by donting the cpsules nd lon of equipment. COMMENTS Bckground There is growing evidence tht colon cpsule endoscopy is relible nd well tolerted dignostic method. A lot of technicl improvements were mde to the cpsule endoscopy, including second genertion, more performnt, colon cpsule. Reserch frontiers Since the introduction of the second genertion Pillcm Colon 2 very few studies ddressed its use fter colonoscopy filure or refusl. Innovtions nd brekthroughs This is 70 ptients pilot study using the second genertion of PillCm Colon cpsule endoscopy to detect colon cncers s well s other tumors in the gstrointestinl (GI) trct. They included heterogeneous popultion t risk of colorectl cncer tht either filed or refused colonoscopy. This study indicted tht PillCm Colon 2 cpsule endoscopy is fesible nd of high cceptnce by ptients. Applictions This study suggests tht PillCm colon 2 cpsule endoscopy my eventully used for popultion-wide colon cncer screening, lthough more cost effectiveness studies re needed. Terminology Pillcm Colon 2 cpsule hs 11.6 mm 31.5 mm in size nd hs been designed to work for t lest 10 h with vrible frme rte (from 4 to 35 frmes/ second in order to correctly visulize the mucos when ccelerted peristlsis). The ngle of view ws incresed to 172 degrees in both cpsule lenses, thus covering lmost 360 degrees of the colonic surfce. Peer review This is n interesting mnuscript describing pilot lot study using the second genertion of PillCm cpsule endoscopy to detect colon cncers s well s other tumors in the GI trct. Although cse controlled studies re ultimtely needed to demonstrte the sensitivity nd specificity of PillCm cpsule endoscopy, this pilot study indicted tht PillCm cpsule endoscopy is fesible nd of high cceptnce by ptients. This study suggests tht PillCm cpsule endoscopy my eventully used for popultion-wide colon cncer screening. This 566 November 16, 2013 Volume 5 Issue 11

9 is descriptive pper on new genertion colon cpsule. Since no comprison with the gold stndrd technique (colonoscopy) is mde specificity nd sensitivity of the method could not be ssessed. One importnt point is tht lesions outside the colon were found nd this point should be underlined. REFERENCES 1 McClements PL, Mdursinghe V, Thomson CS, Frser CG, Crey FA, Steele RJ, Lwrence G, Brewster DH. Impct of the UK colorectl cncer screening pilot studies on incidence, stge distribution nd mortlity trends. Cncer Epidemiol 2012; 36: e232-e242 [PMID: DOI: / j.cnep ] 2 Stock C, Pulte D, Hug U, Brenner H. Subsite-specific colorectl cncer risk in the colorectl endoscopy er. Gstrointest Endosc 2012; 75: [PMID: DOI: /j.gie ] 3 Mlvezzi M, Bertuccio P, Levi F, L Vecchi C, Negri E. Europen cncer mortlity predictions for the yer Ann Oncol 2012; 23: [PMID: DOI: /nnonc/mds024] 4 Dfnis G, Grnth F, Påhlmn L, Ekbom A, Blomqvist P. Ptient fctors influencing the completion rte in colonoscopy. Dig Liver Dis 2005; 37: [PMID: DOI: /j.dld ] 5 Morini S, Zullo A, Hssn C, Lorenzetti R, Cmpo SM. Endoscopic mngement of filed colonoscopy in clinicl prctice: to chnge endoscopist, instrument, or both? Int J Colorectl Dis 2011; 26: [PMID: DOI: /s ] 6 Elikim R, Firemn Z, Grlnek IM, Yssin K, Wtermn M, Kopelmn Y, Lchter J, Koslowsky B, Adler SN. Evlution of the PillCm Colon cpsule in the detection of colonic pthology: results of the first multicenter, prospective, comprtive study. Endoscopy 2006; 38: [PMID: DOI: /s ] 7 Schoofs N, Devière J, Vn Gossum A. PillCm colon cpsule endoscopy compred with colonoscopy for colorectl tumor dignosis: prospective pilot study. Endoscopy 2006; 38: [PMID: DOI: /s ] 8 Spd C, Hssn C, Munoz-Nvs M, Neuhus H, Deviere J, Fockens P, Coron E, Gy G, Toth E, Riccioni ME, Crretero C, Chrton JP, Vn Gossum A, Wientjes CA, Scher-Huvelin S, Delvux M, Nemeth A, Petruzziello L, de Fris CP, Myershofer R, Amininejd L, Dekker E, Glmiche JP, Frederic M, Johnsson GW, Cesro P, Costmgn G. Second-genertion colon cpsule endoscopy compred with colonoscopy. Gstrointest Endosc 2011; 74: e1 [PMID: DOI: /j.gie ] 9 Spd C, Hssn C, Glmiche JP, Neuhus H, Dumonceu JM, Adler S, Epstein O, Gy G, Pennzio M, Rex DK, Benmouzig R, de Frnchis R, Delvux M, Devière J, Elikim R, Frser C, Hgenmuller F, Herreris JM, Keuchel M, Mcre F, Munoz-Nvs M, Ponchon T, Quintero E, Riccioni ME, Rondonotti E, Mrmo R, Sung JJ, Tjiri H, Toth E, Trintfyllou K, Vn Gossum A, Costmgn G. Colon cpsule endoscopy: Europen Society of Gstrointestinl Endoscopy (ESGE) Guideline. Endoscopy 2012; 44: [PMID: DOI: /s ] 10 Leighton JA, Rex DK. A grding scle to evlute colon clensing for the PillCm COLON cpsule: relibility study. Endoscopy 2011; 43: [PMID: DOI: /s ] 11 Yee J, Rosen MP, Blke MA, Bker ME, Csh BD, Fidler JL, Grnt TH, Greene FL, Jones B, Ktz DS, Llni T, Miller FH, Smll WC, Sudkoff GS, Wrshuer DM. ACR Appropriteness Criteri on colorectl cncer screening. J Am Coll Rdiol 2010; 7: [PMID: DOI: / j.jcr ] 12 Sosn J, Sell T, Sy O, Lvin PT, Elihou R, Frifeld S, Libson E. Criticl nlysis of the performnce of doublecontrst brium enem for detecting colorectl polyps > or = 6 mm in the er of CT colonogrphy. AJR Am J Roentgenol 2008; 190: [PMID: DOI: / AJR ] 13 Yucel C, Lev-Toff AS, Mouss N, Durrni H. CT colonogrphy for incomplete or contrindicted opticl colonoscopy in older ptients. AJR Am J Roentgenol 2008; 190: [PMID: DOI: /AJR ] 14 Sli L, Flchini M, Bonnomi AG, Cstiglione G, Citto S, Mntellini P, Mungi F, Menchi I, Villri N, Msclchi M. CT colonogrphy fter incomplete colonoscopy in subjects with positive fecl occult blood test. World J Gstroenterol 2008; 14: [PMID: DOI: / wjg ] 15 de Hn MC, Hllign S, Stoker J. Does CT colonogrphy hve role for popultion-bsed colorectl cncer screening? Eur Rdiol 2012; 22: [PMID: DOI: /s ] 16 Pioche M, de Leusse A, Filoche B, Dlbiès PA, Adenis Lmrre P, Jcob P, Gudin JL, Coulom P, Letrd JC, Borotto E, Duriez A, Chbud JM, Crmpon D, Gincul R, Levy P, ben-soussn E, Grret M, Lpuelle J, Surin JC. Prospective multicenter evlution of colon cpsule exmintion indicted by colonoscopy filure or nesthesi contrindiction. Endoscopy 2012; 44: [PMID: DOI: / s ] P- Reviewers: De Nrdi P, Wng ZH S- Editor: Cui XM L- Editor: A E- Editor: Wu HL 567 November 16, 2013 Volume 5 Issue 11

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