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1 C-III. 하부위장관내시경분야의새로운장비들 Room C 고려대학교의과대학내과학교실 New Enteroscopy, Capsule Endoscopy, Endoscopic Ultrasound, and Others Ja Seol Koo Department of Internal medicine, Korea University College of Medicine, Seoul, Korea 서론내시경기기와수기의발달로위장관질환의진단과치료에서괄목할만한성과가있었으나십이지장제 3부이하부터회장까지의소장은해부학적인구조로내시경접근이매우어려운부분으로여겨져왔다. 1 그러나소장전체를관찰할수있는캡슐내시경과이중풍선소장내시경등여러가지소장내시경이개발되면서소장병변의진단과치료에서다양한접근과활발한연구가진행되고있다. 그리고내시경기구의발전으로내시경선단에초음파변환기 (ultrasound transducer) 를장착한내시경초음파가개발되었고다른영상검사로관찰하기어려웠던소화관벽과주위장기의체계적인관찰이가능하게되었다. 현재내시경초음파는소화관점막아래에위치한종양의진단이나암의국소침윤정도, 췌담도질환을진단하는데필수적인검사로인정되고있다. 이번강의에서는소장내시경과내시경초음파를중심으로최근새롭게개발된내시경기기를살펴보고자한다. 본론 1. 기구보조소장내시경 (Device assisted enteroscopy) 소장의깊은부분의관찰이가능한소장내시경은외측튜브 (overtube), 풍선 (balloon) 등을이용하여굴곡이심한소장으로진입이가능하도록고안된이중풍선소장내시경, 단일풍선소장내시경이있고나선형외측튜브를이용한나선소장내시경등이있다. 1) 이중풍선소장내시경 (Double balloon enteroscopy) 이중풍선소장내시경 (Fujinon, Saitama, Japan) 은내시경, 외측튜브및소장내시경과외측튜브의선단에위치한라텍스풍선의팽창과수축을조절할수있는공기펌프시스템으로구성된다. 이중풍선시스템은소장이과도하게신장되는것을막아주어내시경이쉽게전진하도록도와주며장관의굴곡을해소하고길이를단축시켜기존의밀기법소장내시경 (push enteroscopy) 에비해삽입능력이훨씬향상되었다. 이중풍선소장내시경의외측튜브길이는 140 cm, 내시경작동길이는 200 cm 이며, 내시경직경과부속기채널은진단용내시경 (EN450P5) 과치료용 (EN450T5) 이다른데, 진단용은 8.5 mm 직경, 2.2 mm 부속기채널로구성되며, 치료용은 9.4 mm 직경과 2.8 mm 부속기채널을갖는다. 경구, 경항문또는두가지방법모두를사용하여검사가가능하지만, 전체소장을관찰할수있으나있는비율은 16 86% 로알려져있다. 2 4 캡슐내시경과달리조직생검, 문신 (tattoo), 지혈, 용종절제술, 이물제거, 협착부위확장이나스텐트삽입등시술이가능하다는장점이있다. 5 8 그러나침습적이며일반내시경검사에비해시술시간이길어환자의불편과시술자의노고가많다는단점이있다. 2) 단일풍선소장내시경 (Single balloon enteroscopy) 단일풍선소장내시경 (Olympus, Tokyo, Japan) 은 2006년에처음소개되었으며치료용이중풍선소장내시경과달리내시경선단부에장착된풍선이없고외측튜브에만실리콘풍선이장착되어있다. 단일풍선소장내시경 (SIF Q160) 의작동길이는 200 cm, 직경 9.8 mm, 부속기채널은 2.8 mm로되어있으며, 외측튜브 (ST SB1) 의길이는 132 cm이다. 소장삽입을향상시키기위하여내시경선단부의직경은 9.2 mm로낮추면서 제 49 회대한소화기내시경학회세미나 195

2 Table 1. Comparison Between the Three Enteroscopic Techniques Single balloon Double balloon Spiral enteroscopy Depth of insertion Similar Similar Similar Diagnostic yield Similar Similar Slightly lower Therapeutic interventions Similar Similar Similar Complications rate Similar Similar Slightly lower Duration of the enteroscopy Similar Similar Slightly lower Duration of the sedoanalgesia Similar Similar Slightly lower Learning curve Similar Similar Similar 고해상도영상을유지하였다. 외측튜브는실리콘으로만들어져라텍스알레르기를방지할수있다. 9,10 내시경선단부의굴곡을이용하여내시경을고정하고외측튜브를전진하는방식을이용하며보조자없이시술자한명으로검사를시행할수있다. 11 검사와관련된합병증발생율이 1% 정도로비교적안전한검사법이며, 12 병변진단률 41 65%, 치료성공률은 7 59% 로이중풍선소장내시경과유사한결과를보였다 그러나내시경을이용한고정이잘안되고쉽게미끄러지는단점이있어소장전체관찰률이 12 25% 로낮은편이다. 9,18 상부위장관내시경과대장내시경에도입된향상된영상기술이소장내시경에활용되고있으며최근풍선보조내시경에공초점현미경내시경 (confocal laser endomicroscopy) 을활용한연구가보고되기도하였다. 17 3) 나선소장내시경 (Spiral enterscopy) 2006년 Akerman 에의해처음개발된나선소장내시경 (Spirus Medical, Stoughton, MA) 은외측튜브에나사못의원리를적용하여좀더쉽고빠르게소장의깊은부위까지삽입이가능하도록하였다. 18 나선형의외측튜브 (Endo Ease Discovery SB) 는 118 cm 길이로 5.5 mm 높이의나선형융기가튜브아래쪽 22 cm에위치하는데, 경구로소장에내시경과나선형외측튜브를삽입한상태에서외측튜브를시계방향으로돌려주면소장주름을만들면서내시경이아래로진행하게된다. 항문을통한외측튜브 (Endo Ease Vista Retrograde) 가있으며대장내시경검사가어려운경우나회장검사에이용될수있다. 초기연구에서이중풍선소장내시경, 단일풍선소장내시경보다삽입정도는작았으나시술시간을단축시키는장점이있었다. Discovery SB를이용한연구에서진단율은 33%, 평균삽입길이는트라이츠인대에서 176 cm이었고, 19 다른연구에서평균삽입길이는 262 ± 5 cm, 평균시술시간은 33.6 ± 8 분이었다. 20 나선소장내시경은조직생검, 지혈, 용종절제술과같은치료시술이가능하며, 중증합병증은 0.3%, 천공은 0.27% 로보고되었다. 21 나선소장내시경을이용한검사방법은배우기쉬워서 5 예를경험하면효과적인검사가가능하다고한다. 22,23 표 1 에세가지소장내시경의주요특징을정리하였다. 2. 캡슐내시경 2001 년최초캡슐내시경으로미국 FDA 의승인을받은 M2A (Given Imaging, Yoqneam, Israel) 가시판되어전세계적으로약 2백만명이상에서사용되었고, 24 지난 10여년간기술적으로많은발전이있었다. 현재 5 가지소장캡슐내시경이사용되고있으며, 소장캡슐내시경이모양과크기에서유사하지만기술적으로다소차이가있다 (Table 2). 24,25 그러나, 캡슐내시경의비교연구에서진단율, 영상의질, 전체소장검사율등은유사한것으로알려져있다 캡슐내시경은대체로안전하며약 1-3% 에서합병증이발생할수있으며, 31,32 캡슐저류는소장검사의적응증과관련이있다 그리고예상하지못했던합병증으로캡슐흡인이점차증가하고있다 캡슐흡인은캡슐내시경환자의연령증가와연관이있는데, 캡슐내시경 예중 1예에서발생하고있다. 40 소장캡슐내시경을판독하려면 14,400 72,000 장의영상을확인해야하는데, 이는판독자의집중을필요로한다. 따라서, 이러한캡슐내시경의판독을신속하고용이하게하기위하여여러소프트웨어가개발되어왔다. 처음개발된것은 Suspected Blood Indicator (SBI) 로출혈이나출혈병소를찾기위하여붉은색화소를갖는영상을자동으로수집하는프로그램이었으나정확도에서만족스럽지않았다. 41 최근 Given사는 Fujinon사와협력하여전자색소내시경 (Fujinon Intelligent Chromo Endoscopy, FICE) 을개발하였다. 여러연구에서 FICE를적용한캡슐내시경은소장표면의질감과화질을향상시키는효과가보고되었다 이러한새로운캡슐내시경이소장병변진단에도움이될것으로예상되지만, 임상적의미는현재명확하지않은실정이다. 46 Given사의새로운자료기록기 (data recorder, DR3) 는캡슐내시경의영상을저장하면서동시에분석하여영상촬영속도를적절하게조절하는기능을갖고있는데, 캡슐내시경이정체되어있으면 1초에 4장의사진 196 Korean Society of Gastrointestinal Endoscopy

3 Table 2. Recent Types of Small Bowel Capsule Endoscopes and Characteristics Capsule device Company Country PillCam SB2 Given Imaging, Yokneam MiroCam IntroMedic Co., MC1000-W Seoul EndoCapsule Olympus Co., Tokyo OMOM Chongding (SmartCapsule) Jinshan Science and Technology Co., Beijing CapsoCam SV1 CapsoVision Inc., Saratoga Field of view ( ) Lens LEDs Image sensor Transmission Frames per second (fps) Dimensions (mm) Weight (g) Battery life (h) Realtime imager Reviewing software Optical enhancements Israel 156 Multielement 4 CMOS Radiofrequency 2 4 * Yes Rapid v7 Blue mode FICE 1,2,3 South 170 N/A 4 CMOS EFP 3 ø Yes MiroView v2.5 ALICE Korea colour mode Japan 145 N/A 4 CCD Radiofrequency 2 ø Yes OLYMPUS WS 1 Contrast imaging China 140 N/A 4 CCD Radiofrequency 2 (variable) Yes OMOM N/A workstation United States 360 N/A 16 N/A On board EPROM flash memory (USB) 16 (4 per camera) N/A 15 No CapsoView N/A *PillCam SB2 (L) captures 2 fps PillCam SB2 4 captures 4 fps PillCam SB2 (L) battery life > 11.5 h PillCam SB2 4 battery life 8 h. LED: Light emitting diode; N/A: Not available; CMOS: Complementary metal oxide semiconductor; CCD: Charge coupled device; EFP: Electric field propagation; EPROM: Erasable programmable read only memory; USB: Universal Serial Bus; FDA: Food and Drug Administration; FICE: Fujinon Intelligent Chromo Endoscopy; ALICE: A Large Ion Collider Experiment. 을촬영하고캡슐내시경이움직이면 1초에 35장을촬영한다. 2세대대장캡슐을이용한연구에서캡슐내시경의소장진입과 DR3에의한소장점막의자동확인사이의시간차이는중앙값이 3분 30초로나타났다. 47 캡슐내시경이개발되면서최근까지다양한기술적발전이있었으나, 캡슐내시경의움직임은단지장의연동운동에따라진행하여캡슐의이동을조절할수없다는점은주요한계로여전히남아있다. 이러한한계를극복하기위하여캡슐내시경의이동을조절하고원격조정이가능한기기를개발하기위하여다양한연구가진행되고있다. 48 향후소장병변의정확한진단과조직채취및약물투입이가능한캡슐내시경이개발될것으로기대된다. 3. 내시경초음파 내시경초음파는초음파발생방식에따라기계식과전자식으로분류하고주사방식에따라방사형 (radial scanning) 과굴곡형선형배열주사방식주사방식 (curved linear array scanning) 으로구분할수있다. 최근에사용하는전자식은해상도가우수하며허상이적고컬러 / 파워도플러기능이있어혈행분포를분석할수있고조직하모니상등의영상도얻을수있는장점이있다. 1) 방사형내시경초음파초음파진동자가내시경축에수직으로위치하여 360 환상영상을얻는방식으로넓은범위의단층상을쉽게얻을수있 고, 해부학적으로전산화단층촬영술의영상과같은방향의영상을얻을수있기때문에초심자도이해하기쉽다. 올림푸스사의 GF UM20, JF UM20, GF UM200, JF UM200, GF UMQ200 등과펜탁스사의 EG 3630UR 이현재까지사용되었다. 최근에국내에서주로시판되는방사형내시경초음파는올림푸스사의 GF UM2000 ( 기계식 ) 과 GF UE260 ( 전자식 ), 펜탁스사의 EG 3670URK ( 전자식 ) 가있다. GF UM2000은 5 20 MHz의다양한주파수로변환이가능하고 GF UE260이나 EG 3670URK는 5 10 MHz의주파수로변환이가능하다. 내시경시야는제조사에따라다른데올림푸스사는 55 기울어진렌즈를통해확보되는반면펜탁스사는일반내시경처럼정면렌즈를통해시야를관찰할수있으므로숙련되지않은내시경의사들이조작하기에편리하다. 49 2) 선형배열내시경초음파선형배열방식은초음파의주사방향이내시경의종축방향과일치하므로겸자공을통해삽입한천자침의노출된전장이시야에확보된다. 따라서선형배열내시경초음파는중재적시술에이용되고있지만해부학이다르기때문에시술자가화면을보고익숙해지는데많은시간이걸린다. 올핌푸스사의 GF UC240P, GF UCT240, GF UC2000P, GF UCT2000 등과펜탁스사의 EG 3630U 가현재까지선형배열내시경초음파로이용되고있다. 50 최근정면으로시야를관찰하면서초음파검사를시행할수있는선형배열내시경초음파가올림푸스사에서개발되었으나현재시판되지않고있다. 새로개발된선형배열 제 49 회대한소화기내시경학회세미나 197

4 내시경초음파는일반선형배열내시경초음파보다좁은평면 (90 vs 180 ) 을갖고올림장치 (elevator) 가없고부속기채널직경이 3.7 mm 로되어있다. 51 결론 소장은위치와특성상접근이어려운장기로여겨졌으나최근캡슐내시경과풍선또는특수한외측튜브를이용한소장내시경이도입되면서소장질환의진단과치료에많은발전이있었다. 현재캡슐내시경은침습적이지않으면서소장전체를관찰할수있어소장검사에우선적으로사용될수있으며, 기구보조소장내시경은진단과함께치료시술이가능하여다양한목적으로사용할수있다. 내시경초음파는소화관과소화관주변장기의병변을진단하는데유용하며, 일반적인상부위장관내시경과유사한형태이나상대적으로길고굵은딱딱한선단부및사선방향의시야등으로검사에서합병증위험이있으므로주의가필요하다. 최근광학기술을비롯한다양한기술발전으로새로운내시경기기가개발되고소장을포함한위장관질환의진단과치료에변화가있으나, 새로운기기의임상적의미와효과를규명하기위하여다양한연구가필요하다. 참고문헌 1. Waye JD, Small bowel endoscopy. Endoscopy 2003;35: May A, Nachbar L, Ell C. Double balloon enteroscopy (pushand pull enteroscopy) of the small bowel: Feasibility and diagnostic and therapeutic yield in patients with suspected small bowel disease. Gastrointest Endosc 2005;62: Yamamoto H, Sekine Y, Sato Y, et al. Total enteroscopy with a nonsurgical steerable double balloon method. Gastrointest Endosc 2001; 53: Ell C, May A. Mid gastrointestinal bleeding: capsule endoscopy and push and pull enteroscopy give rise to a new medical term. Endoscopy 2006;38: Nakamura M, Niwa Y, Ohmiya N, et al. Preliminary comparison of capsule endoscopy and double balloon enteroscopy in patients with suspected small bowel bleeding. Endoscopy 2006;38: Heine GD, Hadithi M, Groenen MJ, Kuipers EJ, Jacobs MA, Mulder CJ. Double balloon enteroscopy: indications, diagnostic yield, and complications in a series of 275 patients with suspected small bowel disease. Endoscopy 2006;38: May A, Ell C. Push and pull enteroscopy using the doubleballoon technique/double balloon enteroscopy. Dig Liver Dis 2006;38: Ross AS, Semrad C, Waxman I, Dye C. Enteral stent placement by double balloon enteroscopy for palliation of malignant small bowel obstruction. Gastrointest Endosc 2006;64: Tsujikawa T, Saitoh Y, Andoh A, et al. Novel single balloon enteroscopy for diagnosis and treatment of the small intestine: preliminary experiences. Endoscopy 2008;40: Vargo JJ, Upchurch B, Dumot JA. Clinical utility of the Olympus single balloon enteroscope: the initial US experience. Gastrointest Endosc 2007;65:AB Upchurch BR, Vargo JJ. Single balloon enteroscopy. Gastrointest Endosc Clin N Am 2009;19: Aktas H, de Ridder L, Haringsma J, Kuipers Ej, Mensink PB. Complications of single balloon enteroscopy: a prospective evaluation of 166 procedures. Endoscopy 2010;42: May A, Farber M, Aschmoneit I, et al. Prospective multicenter trial comparing push and pull enteroscopy with the single and double balloon techniques in patients with small bowel disorders. Am J Gastroenterol 2010;105: Kawamura T, Yasuda K, Tanaka K, et al. Clinical evaluation of a newly developed single balloon enteroscope. Gastrointest Endosc 2008;68: Upchurch BR, Sanaka MR, Lopez AR, Vargo JJ. The clinical utility of single balloon enteroscopy: a single center experience of 172 procedures. Gastrointest Endosc 2010;71: Pohl J, Blancas JM, Cave D, et al. Consensus report of the 2nd International Conference on double balloon endoscopy. Endoscopy 2008;40: Neumann H, Vieth M, Fry LC, et al. Introducing BACE balloon assisted confocal endomicroscopy: the first endoscopic technique to perform confocal imaging within the small bowel. Gastrointest Endosc 2012;75:AB Akerman PA, Cantero D. Spiral enteroscopy and push enteroscopy. Gastrointest Endosc Clin N Am 2009;19: Akerman PA, Agrawal D, Chen W, Cantero D, Avila J, Pangtay J. Spiral enteroscopy: a novel method of enteroscopy by using the Endo Ease Discovery SB overtube and a pediatric colonoscope. Gastrointest Endosc 2009;69: Buscaglia JM, Dunbar KB, Okolo PI, et al. The spiral enteroscopy training initiative: results of a prospective study evaluating the Discovery SB overtube device during small bowel enteroscopy (with video). Endoscopy 2009;41: Akerman PA, Cantero D. Complications of spiral enteroscopy in the first 2950 patients. Available from: URL:http//www. gastro2009.org/scien_prog/abstract_detail.php?navid= 93&ssid= Nagula S, Gaidos J, Draganov PV, et al. Retrograde spiral enteroscopy: feasibility, success, and safety in a series of 22 patients. Gastrointest Endosc 2011;74: Riccioni ME, Bizzotto A, Cianci R. How can we compare apples and oranges? Am J Gastroenterol 2010;105: Eliakim R. Video capsule endoscopy of the small bowel. Curr Opin Gastroenterol 2013;29: Fisher LR, Hasler WL. New vision in video capsule endoscopy: current status and future directions. Nat Rev Gastroenterol Hepatol 2012;9: Hartmann D, Eickhoff A, Damian U, Riemann JF. Diagnosis of small bowel pathology using paired capsule endoscopy with 198 Korean Society of Gastrointestinal Endoscopy

5 two different devices: a randomized study. Endoscopy 2007; 39: Cave DR, Fleischer DE, Leighton JA, et al. A multicenter randomized comparison of the Endocapsule and the Pillcam SB. Gastrointest Endosc 2008;68: Kim HM, Kim YJ, Kim HJ, et al. A Pilot Study of Sequential Capsule Endoscopy Using MiroCam and PillCam SB Devices with Different Transmission Technologies. Gut Liver 2010;4: Pioche M, Gaudin JL, Filoche B, et al. Prospective, randomized comparison of two small bowel capsule endoscopy systems in patients with obscure GI bleeding. Gastrointest Endosc 2011;73: Dolak W, Kulnigg Dabsch S, Evstatiev R, Gasche C, Trauner M, Püspök A. A randomized head to head study of small bowel imaging comparing MiroCam and EndoCapsule. Endoscopy 2012;44: Liao Z, Gao R, Xu C, Li ZS. Indications and detection, completion, and retention rates of small bowel capsule endoscopy: a systematic review. Gastrointest Endosc 2010;71: Rondonotti E, Soncini M, Girelli C, et al. Small bowel capsule endoscopy in clinical practice: a multicenter 7 year survey. Eur J Gastroenterol Hepatol 2010; 22: Höög CM, Bark LÅ, Arkani J, Gorsetman J, Broström O, Sjöqvist U. Capsule retentions and incomplete capsule endoscopy examinations: an analysis of 2300 examinations. Gastroenterol Res Pract 2012;2012: Schneider AR, Hoepffner N, Rösch W, Caspary WF. Aspiration of an M2A capsule. Endoscopy 2003;35: Fleischer DE, Heigh RI, Nguyen CC, Leighton JA, Sharma VK, Musil D. Videocapsule impaction at the cricopharyngeus: a first report of this complication and its successful resolution. Gastrointest Endosc 2003;57: Buchkremer F, Herrmann T, Stremmel W. Mild respiratory distress after wireless capsule endoscopy. Gut 2004;53: Leeds JS, Chew TS, Sidhu R, Elliot CA, Sanders DS, McAlindon ME. Asymptomatic bronchial aspiration and retention of a capsule endoscope. Gastrointest Endosc 2009;69: Choi HS, Kim JO, Kim HG, et al. A case of asymptomatic aspiration of a capsule endoscope with a successful resolution. Gut Liver 2010;4: Kurtz LE, Devito B, Sultan K. Small bowel video capsule aspiration with bronchoscopic assisted extraction. Clin Gastroenterol Hepatol 2010;8:e37 e Lucendo AJ, González Castillo S, Fernández Fuente M, De Rezende LC. Tracheal aspiration of a capsule endoscope: a new case report and literature compilation of an increasingly reported complication. Dig Dis Sci 2011;56: Park SC, Chun HJ, Kim ES, et al. Sensitivity of the suspected blood indicator: an experimental study. World J Gastroenterol 2012;18: Imagawa H, Oka S, Tanaka S, et al. Improved visibility of lesions of the small intestine via capsule endoscopy with computed virtual chromoendoscopy. Gastrointest Endosc 2011;73: Imagawa H, Oka S, Tanaka S, et al. Improved detectability of small bowel lesions via capsule endoscopy with computed virtual chromoendoscopy: a pilot study. Scand J Gastroenterol 2011;46: Gupta T, Ibrahim M, Deviere J, Van Gossum A. Evaluation of Fujinon intelligent chromo endoscopy assisted capsule endoscopy in patients with obscure gastroenterology bleeding. World J Gastroenterol 2011;17: Sakai E, Endo H, Kato S, et al. Capsule endoscopy with flexible spectral imaging color enhancement reduces the bile pigment effect and improves the detectability of small bowel lesions. BMC Gastroenterol 2012;12: Spada C, Hassan C, Costamagna G. Virtual chromoendoscopy: will it play a role in capsule endoscopy? Dig Liver Dis 2011;43: Adler S, Hassan C, Metzger Y, Sompolinsky Y, Spada C. Accuracy of automatic detection of small bowel mucosa by second generation colon capsule endoscopy. Gastrointest Endosc. 2012: Kusuda Y. A further step beyond wireless capsule endoscopy. Sens Rev 2005;25: Kim JO, Kim WJ. Radial EUS. Korean J Gastrointest Endosc 2008;36(Suppl 1): Kim EY. Equipments and techniques for the best EUS imaging. Korean J Gastrointest Endosc 2011;43(Suppl 1): Voermans R, Ponchon T, Schumacher B, et al. Forward viewing versus oblique viewing echoendoscopes in transluminal drainage of pancreatic fluid collections: a multicenter, randomized, controlled trial. Gastrointest Endosc 2011;74: 제 49 회대한소화기내시경학회세미나 199

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